Course #2035


Course Material Valid Through/must be completed by
June 2025

Genetic Disorders



Author: Lia Ludlam, BS

The goal of this course is to provide nurses and other health care professionals with a functional understanding of how genes contribute to disease, to help them recognize salient symptoms of the more common genetic diseases, and to train them how to guide patients to resources for coping with genetic disease and accessing treatment.

Learning Outcomes include:

  • Understand DNA function, replication, and mutation and how it relates to disease.
  • Describe symptoms, genetic cause, and available treatment for several genetic disorders.
  • Describe genomic medicine and its inherent opportunities, risks, and impacts on healthcare.

Criteria for Successful Completion

After reading the material, complete the online evaluation. If you have a Florida nursing license or an electrology license you must also complete the multiple choice test online with a score of 70% or better. Upon completion of the requirements you may immediately print your CE certificate of completion.


  • National Center of Continuing Education, Inc. is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation
  • California Board of Registered Nursing Provider No. CEP 1704
  • This course has been approved by the Florida Board of Nursing No. 50-1408
  • Kentucky Board of Nursing Provider No. 7­0031-12-23

Conflicts of Interest

No conflict of interest exists for any individual in a position to control the content of the educational activity.

Expiration Date

This course expires June 30, 2025.

About the Author

Lia Ludlam, BS is a medical science writer based in Texas. Previously, she worked as a researcher in a biology lab investigating neurodegenerative disease. She holds a bachelor's degree in Genetics and Biotechnology from Brigham Young University and is pursuing a master's degree in Technical Communication at Texas Tech University.

Purpose and Goals

The goal of this course is to provide nurses and other health care professionals with a functional understanding of how genes contribute to disease, to help them recognize salient symptoms of the more common genetic diseases, and to train them how to guide patients to resources for coping with genetic disease and accessing treatment.

Learning Outcomes

  1. Understand DNA function, replication, and mutation and how it relates to disease.
  2. Describe symptoms, genetic cause, and available treatment for several genetic disorders.
  3. Describe genomic medicine and its inherent opportunities, risks, and impacts on healthcare.
  4. Describe the roles of genetic counselors and how they can help patients.
  5. Understand a nurse's role in supporting patients who have been diagnosed with a genetic disorder or who are awaiting diagnosis, including supporting their loved ones.
  6. Understand the risks and benefits of participating in clinical research for genetic disease.

1 Introduction

1.1 What is Genetic Disease?

Genetic disease comprises all diseases that are due completely or partially to a person's genetic make-up. There are many kinds of genetic diseases; and a lot is involved in diagnosing and treating these diseases. This course will provide a brief overview of basic genetics, a smattering of specific genetic diseases and their causes, treatment options, and resources for patients with genetic disease.

Occasionally throughout the course, for ease of readability, concepts and processes will be explained using second person pronouns ("you", "your"). Of course, the concepts described apply to your patients as well.

Also, the definitions of bolded terms can be found in the glossary at the end of the course.

1.2 Brief Genetics Overview

As a human race, our genes make us all very similar to each other and simultaneously distinct from one another. Genes give our bodies instructions on how to develop and function properly, and also contribute to the unique aspects of our physical appearance, the way we think, and our personality. Before explaining how genes contribute to disease, it is important to understand what genes are and how they work. Please make sure you understand the vocabulary terms in this section thoroughly as they will be used often throughout the course.

1.2.1 DNA Structure

DNA is a molecule that stores information about how your body should develop and function. It is contained in large quantities inside each of your cells.

The DNA molecule is shaped like a double helix, meaning it is made of two separate strands that twist around each other (see Figure 1.1). The strands are made of billions of nucleotides, which are small units that encode information based on their order in the strand. Nucleotides encode genetic information in a way similar to how '0's and '1's encode digital information in a computer.

DNA Molecule
The DNA molecule is shaped like a double helix. The order of the nucleotides encodes information about how the body should function.
Figure 1.1 A DNA Molecule

Even though DNA can hold the information for how to make thousands of different kinds of molecules, all of that information is contained within just four types of DNA nucleotides. These four nucleotides are called adenine, guanine, cytosine, and thymine.

The two strands of DNA stick together because adenine bonds with thymine and guanine binds with thymine.

The unique order of these nucleotides is what makes you look and function different from a bacteria, a plant, an orangutan, and your neighbor. Interestingly, all human beings have 99.9% of their nucleotide sequences in common.

To keep track of which nucleotide sequences affect which traits, scientists map out the DNA molecules by dividing them into segments called genes. A gene is a sequence of nucleotides that all contribute to a trait. For example, there is a gene in your DNA that gives you your eye color. There is another gene that determines whether your earlobes are attached or free. It is important to note that some traits are controlled by one gene, and some traits are influenced by many. Also, some genes are only known to influence one trait, and some genes influence many.

While the exact number has not been established yet, it is estimated that a person has around 20,000 genes, with an estimated 3 billion nucleotide pairs in total. If unwound, strands of DNA in a one cell would be about two meters long. That is a lot of DNA! How does it all fit in a cell? To conserve space, DNA is wound into very tight bundles called chromosomes. As humans, we have 23 different chromosomes, and we have two versions of each---one from each of our biological parents (see Figure 1.2). A complete set of chromosomes is found inside almost every cell in your body. Your entire set of chromosomes is referred to as your genome.

Human male kerotype
Above is a karyotype of a human male. Pictured are 22 chromosomes, plus the sex chromosomes, making 23 chromosomes in total.
Figure 1.2 Human chromosomes

In summary, DNA is a molecule that contains our genetic information. Depending on the context, it can be referred to in different ways: as the genome, as chromosomes, as genes, or as individual nucleotides, to name a few.

1.2.2 Reproduction and Replication

Now that we have reviewed the basic structure of DNA, let's explore how DNA works. Then we will cover what happens when DNA processes don't work and someone gets a genetic disease.

To start---how did you get your specific sequence of DNA?

It starts with your parents' DNA. Your father, for example, has two of each of his chromosomes. One copy of each chromosome is from his father and one is from his mother. Furthermore, each of those chromosomes is actually made of two DNA molecules called chromatids that are linked together. The two linked chromatids are what make up the traditional "X" shape of chromosomes. You might not be able to see it in the karyotype above, but each of those worm-like strands is actually made of two linked, identical chromatids. Both chromatids within a chromosome are copies of the same genetic information.

To create mature sex cells (the cells the body uses to reproduce, also known as eggs and sperm, or as gametes), the body needs to first divide the number of chromosomes in its sex cells in half. That way, when two sex cells are combined during fertilization, you get two copies of each chromosome in the fertilized egg, rather than four. The cell divides the chromosomes by dividing itself in half. One version of each of the chromosomes goes in one resulting cell, and the other version of each of the chromosomes goes in the other cell.

After the cells divide their chromosome count in half, each of the chromosomes then need to divide in half again. The cell splits up the chromatids by dividing itself in half again, giving each resulting cell gets one of the two chromatids from each chromosome. This process is called meiosis.

In meiosis, a cell with a full set of chromosomes divides in half—twice—to create sex cells that have a single chromatid for each chromosome type.
Figure 1.3 Meiosis

When you were conceived, your birth parents both gave you 23 chromatids (the fertilized egg, or embryo). That means you inherited some genes from your mother in the chromatids she gave you, and some genes from your father in the chromatids he gave you. Some genes might even have recombined slightly to give you traits that neither your mother nor your father have.

Once the egg was fertilized, the chromatids inside the embryo doubled themselves to become full chromosomes (with the typical two-stranded "X" shape, rather than just one-stranded chromatids). Then, the cell with a complete set of chromosomes began to replicate.

In both instances of replication described in the previous paragraph, your DNA made a copy of itself. Here is a brief description of how DNA replicates (see Figure 1.4):

  1. An enzyme (a molecule with a specific function) separates the two strands of DNA, like unzipping a jacket.
  2. Once the DNA strands are separated, a different enzyme begins to fill in the gap by adding the complementary nucleotides. ("Complementary" refers to the way adenine bonds with thymine and guanine bonds with cytosine.)
  3. The same process simultaneously happens on the other original strand. When both strands have finished separating and filling in complementary nucleotides, you now have two identical copies of DNA!
DNA Replication
DNA replicates when enzymes unzip the two complementary strands and copy them. Although the two separated strands aren't identical to each other, when the complementary nucleotides are added, the two double-stranded finished products will be identical to each other.
Figure 1.4 DNA Replication

As your cells continue to divide, they gradually form a larger organism (you!). Each of the replicated cells in your body contains a copy of your DNA.

1.2.3 Transcription and Translation

We've now covered how your specific DNA sequence got into every cell in your body, but now that it is there, what does it do? How does a mere string of nucleotides encode all the information to help us develop and keep us running? In a nutshell, the information in DNA codes for proteins, which are small machines that do work in the body.

To code for a protein, DNA first has to be converted into an intermediary molecule called RNA. This conversion process from DNA to RNA is called transcription. DNA is transcribed using a method similar to replication (see previous section), except that instead of pairing with thymine, adenine will pair with a different nucleotide called uracil.

DNA is transcribed when enzymes unzip the two complementary strands and convert them into RNA.
Figure 1.5 DNA Transcription

Once an RNA molecule is created, it is turned into a protein through a process called translation.

Here is how it works: Every three RNA nucleotides (or codon) codes for one amino acid. Amino acids are the building blocks of proteins. There are 20 kinds of amino acids, each with a different structure and properties. Some amino acids have positively charged pieces attached, and some have negative pieces attached.

Genetic Code
Each 3-nucleotide segment codes for a specific amino acid.
Figure 1.6 Nucleotides Code for Amino Acids

As the RNA strand is translated, each of the amino acids are bound together in a chain. The positive and negative pieces on each amino acid interact with each other, causing the protein to fold up on itself. Each unique amino acid sequence results in a protein with a unique structure and function.

Figure 1.7 RNA Translation

In a multi-step process RNA molecules are converted to amino acids, and an amino acid strand becomes a folded protein.

Each 3-nucleotide segment codes for an amino acid. The amino acids are linked together in different combinations to form different proteins. Proteins perform functions in the body.

There are thousands of different kinds of proteins in your body, with thousands of different functions. Some proteins help your muscles to contract. Others transmit signals throughout the body. Others help protect you from foreign substances in your body. And others help you to replicate DNA or convert it into more protein.

1.2.4 Gene Expression

If the DNA in all your cells is the same, why is a cell in your pancreas so different in appearance and function from a brain cell? Why does your hair feel so different from your toenails?

The answer is gene expression. Even though all your genetic material is present in every cell, a large portion of the DNA is repressed, or prevented from being transcribed and translated into protein. Only the genes that are necessary for the specific cell's function are turned on, or expressed. Therefore, in the previous example, the genes that code for pancreas proteins are expressed in a pancreas cell's DNA, but turned off in a brain cell's DNA. Molecules that attach to genes to turn them off are called repressors.

Speaking of gene expression, how does the body determine which of the two parent genes to express? If one parent has black hair and the other has red hair, why does a person not get a combination of black and red hair? Yet, when one parent is Black and the other is White, a person does sometimes get a blend of both skin colors---in that scenario, it seems that both genes are expressed. How does the body decide?

Sometimes, the gene on one chromosome will suppress the gene on the other chromosome. This gene is called the dominant allele. (An allele is a term for a specific version of a gene). The gene that is repressed is called the recessive allele. With eye color, there are several genes that come into play. Traditionally, eye color was thought to be a Mendelian trait, following only two possible versions of a gene. Simple Punnett squares showing eye color combinations often did not reflect the actual eye color of offspring.

punnett square
This diagram shows the potential offspring of two parents with brown eyes that each have one brown-eye and one blue-eye allele. It shows the parents have a 25% chance of having a blue-eyed child, or a child with two recessive blue-eye alleles.
Figure 1.7 Punnett square

It used to be taught that brown eyes are caused by a dominant allele, so the thought was that if you get just one brown-eye allele from one of your parents, you would have brown eyes. To have blue eyes, you would need two alleles for blue eyes. You would have to inherit the recessive blue-eye allele from both parents.

Researchers have since learned that eyes are caused by more than one gene. There are now prediction charts such as in Figure 1.8.

eue color prediction chart
Figure 1.8 Eye color prediction chart

Many inherited traits that we thought were cut and dry, have turned out to be very complicated---if that were not the case, genetics would be an easy field! There are some traits that are controlled simply by one allele, where one allele is dominant and clearly determines the trait, such as whether or not you have freckles. But for other traits known as polygenic traits, such as your skin pigmentation and height, they are the affected by many expressed genes. Gaining a better understanding of which genes affect which traits is the role of many geneticists and other researchers studying genetics today.

1.2.5 Mutation and other Genetic Alterations

We have learned how DNA works when it is functioning properly. But what about when it doesn't? Whenever a DNA sequence is altered, it is called a mutation. Certain mutations can lead to genetic disease.

Think about the impact of changing one nucleotide in a DNA sequence---let's say that during replication, an adenine nucleotide was added to the sequence instead of a guanine nucleotide by accident. How big of a deal could one wrong nucleotide be? Well, it depends on that nucleotide. When that section of DNA is transcribed into RNA, the section of RNA will have a different sequence. It could code for a different amino acid. The chain of amino acids could fold differently. Depending on which amino acid was affected, the change in the folding pattern could affect the function of your protein. If your protein does not work properly, you could have a serious problem. For example, imagine if the proteins that help your eyes capture light weren't functioning correctly. Or the proteins that carry oxygen in your blood. Not all wrong nucleotides have catastrophic consequences, but some can.

Now imagine if that guanine nucleotide was deleted instead of replaced. Now not only will transcribed RNA and the resulting amino acid be changed for that nucleotide, but the three-nucleotide frame that codes for the right amino acids will have been shifted---now the enzymes that translate the RNA will code for all the wrong nucleotides! There is zero chance that protein will form correctly, or form at all.

Before you start to worry too much, know that the occasional mutation is a natural occurrence. Mutations occur about once every 100 million nucleotides and the body has repair mechanisms to fix them. Sometimes mutations can even cause beneficial traits. Most of the time, a single mutation is not a problem.

There are several degrees of mutation. Single-nucleotide mutations include:

  • Substitution -- when the wrong nucleotide is substituted into the DNA sequence. This type of mutation poses the least risk for harm, since at worst it will only change one amino acid.
  • Addition -- when a nucleotide is added to the sequence. This causes a greater risk for damage, since adding a single nucleotide can throw off the three-nucleotide frame that converts RNA to amino acids.
  • Deletion -- when a nucleotide is deleted from the sequence. This mutation causes a risk for damage similar to that of adding a nucleotide.

Unfortunately, mutations can be larger than just single nucleotides. Sometimes entire genes or even groups of genes can be deleted. Sometimes entire chromosomes will not separate correctly into sex cells during meiosis, and the baby might receive an incorrect number of chromosomes.

When a person inherits mutated DNA that causes significant problems, that person is said to have a genetic disorder.

2 Common Genetic Disorders and Treatments

This section will detail four categories of genetic disorders, some disorders that fall into each category, and the current available treatments for those disorders.

2.1.1 Apert Syndrome

Frequency: Around 1 in 65,000 to 88,000 newborns. The likelihood of inheriting the disease increases with the age of the father.

Average Life Expectancy: Normal

Symptoms: Apert Syndrome (AS) patients will have fusion of the joints, often accompanied by pain and difficulty manipulating objects or walking. AS patients often have facial abnormalities, vision problems, hearing problems, and breathing problems.

Cause: A mutation in the FGFR2 gene on chromosome 10 causes an alteration in the fibroblast growth factor receptor 2 protein, which is the protein that signals to developing cells to become bone cells. When this protein is mutated, it increases its signaling and causes fusion of the bones in the skull, hands, and feet.

Treatment: Surgery is a common treatment for AS, particularly surgical alteration of the fused skull, facial features, hands, and feet. Some AS patients undergo surgery multiple times throughout their life as their bodies continue to grow and develop into adulthood. Sometimes surgery is also required to improve breathing ability.

Living with Apert Syndrome: A Case Study

I’ve seen a lot of doctors in my life. The first doctor I can remember who did surgery on me was in Dallas, Texas. He made sure that I was taken care of, and was very polite and understanding. He was able to give me fingers. My hands were fused together when I was born, so he separated the joints and covered them with skin. He was able to give me more mobility in my hands, and therefore more opportunities to interact with the world.

Some of the hardest things about having Apert Syndrome are being overlooked for a lot of things such as finding a job, dating, and also an assortment of physical pains and aches.

When I apply for jobs and go in for interviews, I wonder if they sometimes think I can’t do the job as well as other people; they go through with the interview because it’s the law, not because they want to hire me. This is disheartening, and makes it harder for me to secure financial stability.

Dating is the hardest on me emotionally because I don’t look conventionally attractive on the outside. Because of this, I wonder if I get overlooked or passed up. Sometimes, people look on the outside, rather than looking inside and seeing good qualities in someone who is disabled. This is frustrating to me, because I want to build a connection with someone.

I also experience muscle, joint, back, and foot pain. For a long time, I couldn’t stand for more than an hour without my feet hurting. This is because of the way my feet are shaped with this disorder. My hands are also not shaped correctly, like my feet, which causes me to lose my grip on things frequently. Living with joint and back pain is something I have had to do and will have to deal with for my whole life.

Sarah V., CA, Patient with Apert Syndrome

2.1.2 Cystic Fibrosis

Frequency: Around 70,000 cases worldwide, with around 30,000 cases in the United States.

Average Life Expectancy: 33.4 years

Symptoms: Mucus buildup in cystic fibrosis (CF) patients can cause many problems, particularly in the lungs. Mucus can block airways, causing breathing difficulties and increasing the risk of bacterial lung infection. Generally, the most serious complications resulting from CF are due to lung infections.

Mucus can also block the pancreas from secreting digestive enzymes. This is called "pancreatic insufficiency." Because of the lack of digestive enzymes, patients with CF might have a history of eating excessively with little weight gain since they have difficulty absorbing nutrients from the food they eat. They might also experience pain, gas, and unpleasant odors after eating due to indigestion. Mucus buildup can also result in chronic inflammation in other organs as well, which can cause further damage.

Other symptoms might include:

  • High levels of salt in the sweat. The standard diagnostic test for cystic fibrosis is a "sweat test." Some hospitals routinely administer sweat tests to infants at 2 weeks after birth so treatment can begin as soon as possible.
  • Blocking of intestines soon after birth
  • Jaundice
  • Cough, potentially with wheezing and production of mucus/blood
  • "Clubbing" of fingers and toes due to oxygen deprivation
  • Inflamed pancreas
  • Nasal polyps
  • Chronic sinus or lung infections
  • Male infertility
  • Delayed puberty
  • Muscle and joint pain

Cause: Mutation of the CFTR (Cystic Fibrosis Transmembrane Regulator) gene on chromosome 7. There are over 900 different known mutations of the CFTR gene.

The protein produced by the CFTR gene works as a channel to let certain ions, particularly chloride, in and out of the cell. If the CTFR gene is mutated, cells will not release chloride ions and the ions will build up in the cells, causing an ion imbalance. The ion imbalance results in the production of a thick, sticky mucus outside the cells.

Treatment: There currently is no cure for cystic fibrosis, but there are several treatments that can ease symptoms and prolong life. Medications that target symptoms include pancreatic enzyme replacements (taken each time the patient eats), antibiotics for the prevention and treatment of lung infections, anti-inflammatory drugs, mucus-thinning drugs to help the patient loosen and cough up mucus, bronchodilators to relax the lung muscles and dilate the airways, and stool softeners. Other medications target the mutated gene or mutated protein.

2.1.3 Fragile X Syndrome

Other Names: Martin-Bell Syndrome

Frequency: About twice as many males (1 in 4000) than females (1 in 8000) are diagnosed with Fragile X Syndrome, and the symptoms are usually more severe in males.

Average Life Expectancy: Normal

Symptoms: Fragile X Syndrome (FXS) patients sometimes show signs of mental retardation, usually evident early in life. These signs might include not meeting developmental benchmarks such as sitting, standing, walking, or language development. FXS patients often show signs of hyperactivity (high energy levels, agitation, hand-flapping, etc.). About 15% of individuals with FXS are diagnosed with autism.

Cause: A mutation in the fragile X mental retardation 1 (FMR1) gene, located on the X chromosome, causes reduced levels of the fragile X mental retardation protein (FMRP). FMRP is necessary for synapse development in the brain.

Treatment: Occupational therapy, behavioral therapy, and physical therapy can all improve symptoms, especially if the patient begins therapy early in life. Medications for mood stabilization, ADHD, and sleep improvement are also often used with FXS patients.

2.1.4 Huntington's Disease

Frequency: 3 to 7 per 100,000 people of European ancestry. Appears to be less common among other ancestries.

Average Life Expectancy: In most cases, HD symptoms begin in the 30s or 40s, and death usually occurs 10 to 20 years after the first symptoms. Juvenile HD can occur patients with a very high number of "CAG" repeats (closer to 60). These patients live 10 to 15 years after the onset of symptoms.

Symptoms: Early manifestations of Huntington's disease (HD) include psychiatric problems such as depression, anxiety, agitation, impulsivity, apathy, social withdrawal, and obsessiveness. Cognitive symptoms also begin to develop, such as reduced perception, memory, and learning ability. HD patients also manifest a movement disorder called chorea, which is abnormal and involuntary movements. Chorea typically involves twisting movements of the face, limbs, and body. Signs and symptoms become more severe as the disease progresses.

Cause: Excessive repeats of the "CAG" codon on the HTT gene (chromosome 4) result in extra-long versions of the huntingtin protein. Normal HTT genes have 10-35 repeats of the "CAG" codon, whereas Huntington's disease (HD) patients have 36-60. The extra-long huntingtin proteins break into pieces that can float around the cell and block neural activity. Eventually the affected neurons die, causing mental, emotional, and physical dysfunction. This mutation is autosomal dominant. More CAG repeats tend to be inherited each time the disease is passed on.

Treatment: There is no cure or treatment to slow the progress of HD, but there are treatments to reduce symptoms. Behavioral, speech, and occupational therapy can help. It is recommended that patients consider starting treatment in the earlier stages of disease progression. Patients can also take mood-stabilizing medications, antipsychotics, or medications to help with chorea.

2.1.5 Sickle Cell Disease

Frequency: Around 100,000 Americans currently have SCD. It is most common among peoples of African, Mediterranean, and Hispanic descent.

Average Life Expectancy: Median life expectancy is around 45 years.

Symptoms: Blockages result in pain, usually in back, chest, extremities, and abdomen. Blockages also result in decreased oxygen to organs and tissue leading to increased infections and organ failure. As a result of a lower red blood cell count, patients can also become anemic which can result in fatigue, delayed growth, or jaundice. Typically, patients are asymptomatic when not experiencing a sickling episode.

Cause: A mutation in the Beta-globin (HBB) gene on chromosome 11 results in the production of fewer, red blood cells. The cells that are produced tend to have a sickled shape. The HBB gene is responsible for the formation of hemoglobin, which is the protein in red blood cells that allows the cells to transport oxygen. When the hemoglobin protein is mutated, it changes shape and causes the red blood cells to become sickle-shaped. The malformed red blood cells can pile up and cause blood vessel blockages. Mutated red blood cells also live for 10 to 20 days versus around 120 days for normal red blood cells. With less healthy cells circulating, patients can become chronically anemic.

Patients only develop sickle cell disease (SCD) when they inherit a mutated gene from both parents. Otherwise, they only inherit what is called "sickle cell trait." People with only one copy of the gene do not show symptoms.

Treatment: The only cure for SCD is bone marrow transplant or stem cell transplant. However, transplants come with their own risk and are only used in severe cases. In other cases, the following palliative measures are taken:

  • Antibiotics and vaccines to help prevent infection
  • Oxygen therapy
  • Anticoagulants to help prevent blood clots
  • Pain relievers
  • Blood transfusions

In March of 2021, the FDA approved a four-year clinical trial in humans to test a CRISPR-based curative treatment to correct the gene mutation in the beta-globin gene. Also in 2021, the FDA granted accelerated approvals for voxelotor for adults and children 4-11. The treatment that has been shown to increase hemoglobin's ability to bind to oxygen, thus reducing the sickling shape and its effects.

2.1.6 Thalassemia

Frequency: Thalassemia is one of the more common diseases worldwide, but it is fairly rare in the United States. Estimates of prevalence vary widely.

Average Life Expectancy: Normal life expectancy with proper treatment.

Symptoms: Both types of thalassemia manifest in the first two years of life. Thalassemia minor is normally asymptomatic, but may involve mild to moderate anemia (fatigue, dizziness, headache, shortness of breath). Thalassemia major can delay both physical and mental growth and result in increased risk of infection. Thalassemia major can cause subsequent diseases including jaundice, splenomegaly, hepatomegaly, and cardiomyopathy.

Cause: Like SCD, thalassemia is also caused by an autosomal recessive mutation in the HBB gene. This particular mutation results in inadequate production of hemoglobin, leading to a decrease in red blood cells.

If a person has one normal gene and one affected gene and the symptoms are mild, then the condition is called "thalassemia intermedia" or thalassemia minor. However, if the person has two affected genes then the condition is called "thalassemia major," or Cooley anemia which is life-threatening.

Treatment: Patients with moderate or severe thalassemia will likely require blood transfusions. More severe cases require more frequent blood transfusions. Sometimes patients are treated with iron chelation therapy and prescribed folic acid to help with anemia.

2.1.7 Familial Hypercholesterolemia

Frequency: 1 in 200-250 people

Average Life Expectancy: Life expectancy may depend on whether the person has heterozygous or homozygous FH. With heterozygous HF, life expectancy can be decreased by 15-30 years. However, it is common for patients with homozygous FH to die before they reach 20 years old. If FH is detected and monitored early in childhood, a patient's likelihood of a heart attack is greatly reduced.

Symptoms: Xanthomas (fatty growths on the skin) or bumps may appear around the body. Patients may also experience chest pain if the plaque buildup is in the coronary artery walls. Heart failure occurs fairly early in life.

Cause: A mutation in the low-density lipoprotein receptor (LDLR) gene on chromosome 19 causes the LDL receptors on cells to malfunction, preventing LDL from being absorbed into cells. When LDL is not properly absorbed into cells, it increases LDL count in the bloodstream which can lead to plaque on artery walls (atherosclerosis).

There are two forms of familial hypercholesterolemia (FH): heterozygous FH occurs when the mutated gene is inherited from only one parent and homozygous FH occurs when the offspring inherits the gene from both parents. Heterozygous FH is less severe than homozygous FH.

Treatment: Treatments include a low-fat diet, exercise, and lipid-lowering drugs such as statins. Combination therapies using statins, bempedoic acid, ezetimbe, and PCSK9 can result in lower Low-Density Lipoprotein Cholesterol (LDL-C).

2.2 Chromosomal Disorders

The following disorders are caused by the alteration of all or part of a chromosome. There are many more chromosomal disorders; the following are just a few.

2.2.1 Down Syndrome 

Other Names: Trisomy 21

Frequency: 1 in 700 newborns. The chance of having a child with Down syndrome increases with the mother's age.

Average Life Expectancy: About 60 years.

Symptoms: Symptoms can vary in severity, but typically include physical growth delays, characteristic facial features such as a round face and slanted eyes, a ruffle of skin on the back of the neck, and mild to moderate intellectual disability. Patients with Down Syndrome (DS) are also at an increased risk for heart, vision, and hearing problems. Approximately 30% will be diagnosed with Alzheimer's in their fifties.

Cause: An additional copy (or part of a copy) of chromosome 21 results in a series of characteristic features.

Treatment: There is no cure for Down syndrome. However, early treatment programs can help improve skills such as speech, physical, occupational, and/or educational therapy.

Raising a Child with Down Syndrome: A Case Study

What are some of your experiences regarding your child’s symptoms of the disorder?

In general, Carmen grew up on a “relaxed” development path. She had a Patent Ductus Arteriosis (PDA) that was corrected with a catheterization at 9 months. Heart defects are very common in Down syndrome, and we were fortunate that she had one that could be corrected without open heart surgery. She did not have any other major medical issues besides hip dysplasia, which is also common in DS and required surgery. We homeschooled her like we did our other two children, and other than moving through the grades more slowly, she worked hard at school and loved/loves to learn new things. She topped out at about grade 3-4. She is a good reader, but comprehension is more difficult for her. She tends to think concretely, so sometimes you have to explain things to her differently than other people so that she can understand. She had difficulty producing clear speech, which is a common problem with DS. Interestingly, when we entered her in a 4H speech competition and really focused on diction in a short speech, it made such a difference, and all of a sudden she was able to engage in conversations with strangers and be understood. It was like a lightbulb went off. If she slowed down and really focused on enunciation, all of a sudden people reacted very differently and engaged her in conversation. She loves to entertain, and her favorite place to be is on a stage with an audience. It doesn’t matter what she’s doing—she loves to dance, sing, do ventriloquism, play the ukulele, and act in plays. Being very social is another very common trait of people with DS.

What is something that the average person might not know about the disorder?

We have always raised our daughter to be very independent, and so she is much less limited than what the average person expects. She is social, funny (she has an infectious laugh), and is really very capable. She does things that many average people recognize as significant skills, like snowboarding, playing the ukulele, doing ventriloquism (and she doesn’t move her mouth when it’s the puppet’s line!)

When did you know your child had the disorder? How did the diagnosis make you feel?

We had a prenatal diagnosis, and after a few days of disappointment, we just got busy doing our research and getting on with it.

Do you have any notable experiences (good or bad) with healthcare professionals in relation to treating the disorder?

Our genetic counselor was wonderful. She really took her cues from us, allowing us to ask our questions instead of bombarding us with information and pamphlets. And we did ask a lot of questions!! The doctors were not so good - they pressured us towards abortion, both overtly and subtly, and in general acted like she was damaged goods. The single exception was our cardiologist, who mostly just gave us the facts about her heart, but in an early exam commented how beautiful her eyes were with the Brushfield spots (white spots where most people have dark spots in their eyes).

Mark and Ginger H., MD, Parents of Child with Trisomy 21 (Down syndrome)

2.2.2 Duchenne Muscular Dystrophy

Other Names: DMD, dystrophinopathy, pseudohypertrophic myopathy

Frequency: 1 in 3,500 to 5,000 male newborns worldwide. The disease almost exclusively affects males.

Average Life Expectancy: Although the average life expectancy is around 27 years old, survival into the early 30s is becoming more common.

Symptoms: Because patient's muscle tissue is weakened and does not regenerate properly, symptoms include progressive weakness of major muscle groups. Eventually this weakening leads to the inability to walk, cardiomyopathy, respiratory failure, and mental impairment.

Cause: Mutations in the dystrophin (DMD) gene on the X chromosome cause dysfunctional dystrophin protein. Dystrophin is the protein needed to keep muscle fibers intact. When this gene is mutated, muscle fibers are susceptible to damage.

Because the disorder is due to a mutation on the X chromosome, the disease tends to affect mostly males. Females, while they might have one affected X chromosome, usually also have a healthy X chromosome as well and thus are less likely to show symptoms. However, a female with one affected chromosome has a 50% chance of passing the gene on to her children.

Treatment: Corticosteroid therapy may slow disease progression for up to two years. The main treatment for DMD is to preserve mobility and independence through exercise, physical therapy, and assistive devices.

2.2.3 Klinefelter Syndrome

Other Names: XXY syndrome, 47, XXY syndrome.

Frequency: 1 in 650 males, but some researchers think that 75% of cases go undiagnosed.

Average Life Expectancy: Close to Normal

Symptoms: Symptoms may be so mild as to go unnoticed, until into adulthood. Men with KS tend to have longer legs and arms than their family members, larger breasts (gynecomastia), and lower amounts of testosterone. Often, lower testosterone result in lower muscle mass, less facial hair, and low fertility. Approximately 10% of KS patients with KS also have autism. KS patients have a slight elevated risk of type-2 diabetes, intellectual and mood disorders, and venous disease.

Cause: At least one extra "X" chromosome in males. Males with Klinefelter syndrome (KS) have three or more sex chromosomes (XXY) instead of the normal two. An error occurs when an x chromosome does not get distributed properly during division and either the egg or sperm ends up with an extra copy of the x chromosome.

Treatment: Testosterone replacement therapy, breast surgery, speech/behavioral/physical therapy, and fertility treatment can all offset the symptoms of KS.

2.2.4 Turner Syndrome

Other Names: 45,X syndrome, Ullrich-Turner syndrome, Bonnevie-Turner syndrome.

Frequency: 1 in 2,500 newborn girls worldwide. (It is also a common cause of miscarriages and stillbirths.)

Average Life Expectancy: Close to normal, especially if comorbidities are treated.

Symptoms: Many women with TS have a short stature, with skeletal abnormalities. It is common for the ovaries to not develop properly, so many women with TS do not naturally undergo puberty and are infertile. Some women with TS have wide, webbed necks and lymphedema. Infants may have puffy hands and feet that can resolve by early childhood Up to 80% will have ear formation and hearing loss issues. Up to 50% have cardiac defects. Often TS brings along with it comorbidities such as heart problems, obesity, and osteoporosis (due to low levels of estrogen).

Cause: A missing or partially incomplete X chromosome in females results in stunted physical and sexual development.

Treatment: Hormone replacement therapy can help females with TS to undergo puberty (although most women with TS will still remain infertile), increase stature, and reduce osteoporosis. FDA has approved the use of recombinant growth hormone in children with TS. Most females with TS will need sex hormone replacement therapy to undergo puberty and maintain secondary sex characteristics.

2.3 Complex Disorders 

The following are diseases that are concurrently influenced by a variety genetic, environmental, and lifestyle factors. Often, there is no one clear gene or external factor that results in the onset of these diseases or determines their severity. Rather, a person is more likely to have the disease if they have a higher number of related genetic variations and external factors. Researchers are still trying to determine the specific causes of these diseases.

2.3.1 Alzheimer's Disease

Frequency: In the United States, 1 in 9 people over the age of 65 has Alzheimer's disease. The number of patients with Alzheimer's disease is projected to more than double by 2050.

Average Life Expectancy: Usually 8 to 10 years after the onset of symptoms, although it can vary significantly.

Symptoms: The most common symptom of Alzheimer's is memory loss, which worsens throughout the progression of the disease. Patients with AD might also undergo personality changes and become more anxious, distant, despondent, or irritable. They might begin to struggle with language skills.

Cause: There are many genes associated with the onset of Alzheimer's disease (AD), but some of the more prominent are the APOE, APP, PSEN1, and PSEN2 genes. These genes relate to the creation of amyloid, a type of plaque that can build up in the brains of patients with AD. Other factors related to the cause of AD involve the buildup of tau protein inside brain cells. The buildup of both amyloid and tau proteins can lead to inflammation in the brain. Protein buildup and inflammation results in neural damage and death. Other factors that have found to increase the likelihood of developing AD include heavy alcohol consumption, obesity, high cholesterol, chronically poor sleep, and having Down syndrome.

Treatment: Most patients require constant care by the end stages of the disease. Care providers usually need to provide assistance with eating, bathing, dressing, and other daily activities. Some treatments that alleviate and may even slow symptoms are cholinesterase inhibitors, anti-depressants, anti-psychotics, improved nutrition, and exercise.

2.3.2 Attention Deficit Hyperactivity Disorder (ADHD)

Frequency: Up to 5% of children worldwide and 5% of adults worldwide.

Average Life Expectancy: Normal

Symptoms: Patients with ADHD often have difficulty sustaining attention, are hyperactive, and act impulsively. These behaviors can lead to weakened social development, trouble performing in school, and feelings of low self-worth.

Cause: There are dozens of gene variations that are related to Attention Deficit Hyperactivity Disorder (ADHD), although it is very rare that a mutation in just one gene will lead to the onset of the disease. Instead, a person's risk of having ADHD increases based on how many related genetic variants they have in their genome. Scientists are still unsure about the specific neurological cause of ADHD. Besides genetics, ADHD has also been linked to exposure to toxins (particularly lead), maternal alcohol consumption/drug consumption/smoking during pregnancy, or premature birth.

Treatment: Stimulant medications can help improve the function of neurotransmitters in the brain. Behavioral therapy and educational assistance can also be helpful. There is no cure for ADHD, although symptoms can improve in some individuals as they get older.

2.3.3 Autism Spectrum Disorder

Frequency: 1 in 54 children. It is four times more common in males than in females.

Average Life Expectancy: Normal

Symptoms: Symptoms can vary widely. Patients with ASD tend to show difficulty socializing and communicating and tend to be more comfortable interacting with objects than with people. Patients with ASD can sometimes engage in repetitive behaviors or obsession with one topic or thought. Autism has been associated with the co-occurrence of psychiatric disorders, most notably anxiety-related disorders.

Cause: Over 1,000 genes have been reported to be related to Autism Spectrum Disorder (ASD) and many of the genes are related to brain development. However, having a variation one gene alone is rarely responsible for causing the disorder. Researchers are not sure about the exact causes of ASD.

Treatment: There is no cure for ASD, but behavioral, communicative, and educational therapies can be very useful. Sometimes medications such as anti-depressants, antipsychotics, or medications for hyperactivity can be helpful as well.

Rethinking the Term “Disorder”: A Case Study

I would like to shed some light on my “disorder.” I see the term disorder as a derogatory term, as though something is in a state of disarray, or as though my present condition should not be the way that it is. Imagine the human brain as a sort of electronic circuit board. Circuit boards can come in a variety of shapes, sizes, and designs, all suited for various tasks and purposes. Same goes for brains: why some people’s brains are “wired” differently than others. One patient may struggle with depression, another may struggle with antisocial personality disorder, or in my case, I have autism. Just think of it as my brain being wired a little differently.

Throughout my life, it never really occurred to anyone, including my own immediate family, that I struggled with any form of autism. I was quite a social child. I made friends somewhat easily, I was outgoing, and enjoyed some hobbies that any normal child my age would. The one thing that made me suspect I had autism, however, came to me when I was in high school. Whereas most teens my age were interested in dating, getting a car, or so many other typical teenage preoccupations, I was interested in inventing, video games, and comics, and sci-fi. So much so that I started to get stunted socially, which is also part of autistic behavior. I used very advanced vocabulary that often was misunderstood by my peers. I would often start conversations with friends about new inventions I wanted to build, a new video game I enjoyed, a new comic or novel I had read, and so on. It soon became too difficult for me to even carry on a normal conversation that was not dominated by any of my topics of personal interest. My friendships stumbled, and I had many difficulties dating.

In my case, I enjoy the act of social interaction. The only problem is I just do not know how to interact or function in a social situation sometimes. Some days I can hold eye contact with the other party, and on others I cannot look anyone in the eye. Some days I say too much in a conversation, others I cannot find the right words to say. Most of the time however, I wind up saying or revealing much more than is necessary, and it is off-putting to those around me.

As time goes on, I have begun seeing having autism as an advantage. Some people think that people with autism have difficulty learning, which is not at all true. In fact, I learn things very quickly, much faster than my peers in some cases, and I attribute that skill to my mildly autistic behaviors. I can also focus on important matters with laser-like focus.

It is possible for some people to lead perfectly functional lives with autism. It honestly just comes down to a matter of balance. Over time, I have come to accept and even embrace it as a part of me. It has its pros and cons like anything else, but all in all it can be a blessing more than it is a curse.

Justin B., Texas, patient with autism spectrum disorder

2.3.4 Breast Cancer

Frequency: 1 in 8 women in the US. Men can have breast cancer as well, but they only represent 1% of cases.

Average Life Expectancy: Life expectancy depends on how long the patient has had the cancer and how old the patient is at the time of diagnosis. The overall survival rate is between 80-90%, however the five-year survival rate for those whose cancer has spread to distant parts of the body is 28%.

Symptoms: Some signs of breast cancer include abnormalities in the breasts, such as change in breast shape or size or the presence of a lump or tissue thickening in the breast area. Signs can also include changes to the nipple such as discharge, turning inward, or soreness. Sometimes the skin on the breasts can become red, dimpled, or scaley.

Cause: The presence of the BRAC1 gene or BRAC2 gene have a high correlation of breast cancer risk, and other, less correlated variations have also been identified with higher risk. However, a large percentage of genetic risk does not come from inherited mutations, but from the accumulation of somatic mutations during a person's lifetime. Some factors that increase the likelihood of somatic mutations include obesity, hormone treatments, alcohol consumption, and never being pregnant. Both inherited and somatic mutations cause cancer by altering the cell's ability to regulate growth, causing out-of-control cell replication that can cause blockages and inflammation.

Treatment: Surgery, radiation therapy, chemotherapy, and hormone-blocking therapy are all potential treatments. Surgeries might involve the removal of only the tumor, of one breast, or of both breasts.

2.3.5 Crohn's Disease

Frequency: 100-300 per 100,000 people

Average Life Expectancy: Normal with proper management.

Symptoms: Inflammation of the digestive tract can lead to open sores, intense abdominal cramping, blockage of the tract from the buildup of scar tissue on the abdominal walls, diarrhea, and fever. Sometimes fistulae can form---fistulae are abnormal connections between different organs. In CD patients, most fistulae occur between different sections of the intestines, or between the intestines and the abdominal wall. These symptoms can then lead to weight loss, fatigue, and anemia.

Cause: Over 200 genetic variants can cause Crohn's disease (CD). NOD2, ATG16L1, IL23R, and IRGM are a few of the major genes that have been identified with CD and are related to immune system function. It is likely that when these genes are mutated, the body cannot properly respond to certain bacteria in the digestive tract, resulting in inflammation. Other lifestyle factors such as smoking have been linked to CD. Some research show that a diet high in fat and sugar might contribute to CD, but the connection remains tentative. Crohn's also tends to occur more in individuals in urban locations, and among people of Northern European and Ashkenazi Jewish ancestry.

Treatment: Although CD cannot be cured, some CD treatments include antibiotics to minimize inflammatory bacteria, immune system suppressors, anti-inflammatory drugs, anti-diarrheals, and even surgery to remove damaged parts of the intestinal tract. Sometimes patients are put on special diets to minimize fiber or increase nutrient intake.

Human Chromosome Diseases
Diagram of the human chromosome set, showing the location of some genes whose mutant forms cause hereditary diseases. Conditions that can be diagnosed using DNA analysis are indicated by a red dot.
Figure 2.1

Living with Crohn’s Disease: A Case Study

I found out I got Crohn’s Disease when I was 18. Before then, I never had any kinds of illness—no flu, no fevers. I never missed a day of school. But in my senior year of high school, I started getting symptoms that would come for about 2 weeks and then leave me for about 2 weeks, which made it hard to get in to see a doctor. One day my mom noticed blood in the toilet. She took me to the hospital as fast as she could where they diagnosed me with Crohn’s.

In the past 12 years, I have not had one single bowel movement that has not hurt me. I am always in pain when using the bathroom. No medicine has cured that part of me yet. Before bowel movements, I usually have a daily flareup that is about 20-30 minutes long. I call it "that time of the day." I can never choose when this time of the day comes.

When I have a flareup, I always need to find a bathroom. It means that I need to leave whatever I am doing, either school or work or being with friends, and I can’t come back until the flareup has ended. I am always afraid of having flareup bowel movements in public bathrooms because sometimes the pain is so strong you can hear my heavy breathing and it sounds like I’m in the middle of a heart attack. Private bathrooms for bowel movements or flareups is my safe space. The flareups can have different severities: I can usually tell how much time I have to get to a bathroom by how dull the pain is. On a 1-10 pain scale, when I feel a dull 1-2 pain it usually means I have about 10-15 minutes to find a bathroom. If it's a sharp 3-6 (which happens about half the time), I have less than 5 min to find the bathroom. When it is a pain of 7-10, I am usually on the floor with pain and unable to move.I call those instances my “contractions.” They come and go, with 5 min of pure pain and then 1-2 minutes of being able to walk away and try to find the nearest any bathroom possible. During the pain I usually have a hard time breathing and sadly during those few minutes I wish nothing more than for someone to murder me.These contractions come with depressive episodes that last as long as the flareups last. Usually if I have severe pains, the bowel movement usually has blood with it.

Another big thing about the flareups is that depending on the pain level, it takes a lot of energy out of me. It's like a workout, all my muscles tense up. If it's a light flareup, I can usually continue my day like I had before the flareup. If my flareup level reached anything over a 5, I am usually out of energy for the rest of the day. It's especially bad if they happen towards the beginning of the day. I would like people to know that as a Crohn’s patient, I run out of energy faster than the average person so they can accommodate for that.

I have had many good doctors throughout this time. I was very lucky that I started with a world-famous gastroenterologist, Dr. Dubinsky in Cedars-Sinai Los Angeles. I have had my ups and downs with my Crohn’s, but I have had doctors monitoring me now for 12 years, so I know I am in good hands.

Tal S., from Israel currently living in Utah, patient with Crohn’s disease

2.4 Mitochondrial Disorders

Mitochondrial disorders are a group of genetic disorders that are often inherited, although it is possible for them to occur spontaneously. When they are inherited, they can be inherited one of two ways: through nuclear DNA (like the other disorders described in this section) or through mitochondrial DNA. If the disorder is inherited through mitochondrial DNA, it is thought to be exclusively inherited through the mother. Although exclusive inheritance through the mother is considered tenet in biology, research from the Cincinnati Children's hospital reported in Nature in 2019 suggests that in some exceptional circumstances biparental transmission may occur. In other words, the group has posited that paternal mitochondrial DNA may also be passed to offspring in rare cases.

Mitochondria are small structures inside each cell that are responsible for producing energy. They are essential to the functioning of every organ in the body. Interestingly, mitochondria have their own DNA, separate from the nuclear DNA present in the cell.

In mitochondrial disorders, there is generally a lack of functioning mitochondria in the cell, which means the cell cannot produce enough energy. This results in cell damage and cell death throughout the body, including the brain and major organs.

Mitochondrial disorders occur about 1 in 85,000 people.

Many mitochondrial disorders have many symptoms in common, such as loss of mental capability (dementia), loss of ability to move, and spastic movements. Other common symptoms are deafness, blindness, and liver disease. Many patients with mitochondrial disorders do not live past childhood. Unfortunately, there are few treatments for mitochondrial disorders beyond physical therapy to help with controlling spasticity and maintaining muscle tone.

Some of the more common, more serious mitochondrial disorders include Alpers' syndrome, Complex I Deficiency, and Leigh syndrome. Leber hereditary optic neuropathy is a more mild disorder in that a patient will have a normal life expectancy however it does result in vision loss.

3 Genomic Medicine

Now that you know a bit more about different genetic diseases, let's discuss the field of medicine that treats them: genomic medicine. But first, it is important to understand the definition of precision medicine. Precision medicine is the tailoring of a patient's treatment based on their lifestyle, environment, biomarkers, and genetic makeup.

In the past, precision medicine was referred to as "personalized medicine." However, this term has changed over time because the word "personalized" gave the impression that every treatment was individualized for every patient. In reality, precision medicine identifies which groups a patient falls into (for example, their age gender, ethnicity, blood type, particular sequences of particular genes, etc.) and then draws on large-scale research to know which treatments work best for people in that group.

Genomic medicine, a subspecialty of precision medicine, is the medical discipline in which a patient's genetic information determines the type of clinical care they will receive. Genetic information is typically gathered through DNA sequencing and family trees. As an example: to determine which medication will work best for a leukemia patient, a doctor will sequence the DNA of the patient's cancer cells. The doctor will then draw from previous research to know which medications work particularly well when a person's cancer cells have that particular DNA sequence.

The field of genomic medicine also considers the ethical implications of deciding whether/how to collect genetic information, how to respond to that information, and the implications of altering the human genome. These considerations will also be covered in this section.

3.1 Genetic Testing

We cannot see our DNA, and even if we could, it takes an expert to know which nucleotide sequences correspond with which traits and which sequences can result in a genetic disorder. Therefore, we rely on medical professionals to collect and interpret our genetic data. There are currently over 1,000 types of genetic tests available. Some genetic tests look at DNA sequences, some look at chromosomal patterns, and others look at the protein activity profiles in the body. Genetic testing is the fountain of information that gives life to genomic medicine.

3.1.1 How Does Genetic Testing Work?

First, a patient's genetic material has to be collected. This is generally through a cheek ("buccal" swab), a spit sample, or a blood sample. Then the sample is sent to a laboratory, where it sequenced using special equipment.

Typically, a doctor will request sequencing for a particular section (or sections) of a person's genome---the genes relevant to the disease(s) in question. On occasion, a person's whole genome will be sequenced, but this is usually not necessary.

The sequencing center will send back a report to the doctor that requested the test. Sometimes the doctor is trained to interpret the sequence results, other times the doctor will send the results to a genetic counselor for interpretation.

3.1.2 When Should a Patient Get Genetic Testing?

Different tests help patients in differing circumstances. A variety of genetic tests are described below to help you grasp the scope of genetic testing.

Diagnostic testing

Genetic diagnostic testing refers to any genetic test that indicates the presence of a disorder. It can be conducted at any stage in a person's life. If a genetic disorder is suspected, diagnostic testing can confirm or rule out a diagnosis if a test for that genetic disease is available.

Carrier testing

Unlike diagnostic testing, carrier testing detects whether a person carries only one copy of a gene that codes for a disorder (rather than both copies). Carriers usually will not be tested because they are concerned about having a genetic disorder, but rather if they are concerned about their giving a disorder to their future children. A person might be a carrier if they have a history of a certain disorder in their family, or if their ethnicity predisposes them to a certain disorder. If both parents suspect they might be carriers, they might both be tested to determine the likelihood of having a child that inherits both carrier genes and therefore develops a disorder. This can help them in their family planning decisions.

Preimplantation testing

Preimplantation testing can help a couple decrease the odds of their child having a genetic disorder. Parents might consider this type of testing if they know they both carry an allele for a disorder that they could potentially both pass on to their child. To make sure that an embryo (a fertilized egg) does not have a genetic disorder, parents can use in-vitro fertilization, or the combining of eggs and sperm outside the woman's body in a laboratory environment. This enables testing of genomes of the embryos to be tested for potential disorders. Embryos that do not carry the genes for the disorder are then implanted into the woman.

Prenatal testing

After an embryo begins to grow and becomes a fetus, the genome of the fetus can be tested by extracting a small amount of amniotic fluid from the mother and analyzing the baby's DNA found in the fluid. Knowing the likelihood that a fetus has a disorder can help parents make decisions about the pregnancy and lessen uncertainty about the future.

Newborn screening

Some genetic diseases, if caught early enough, can be treated to the point that more severe symptoms are prevented. That is why some newborn genetic screenings are mandatory nationwide.

Three screening tests that are mandatory across the country include:

  • Phenylketonuria (PKU), a condition in which the body is unable to break down the amino acid phenylalanine. Phenylalanine is essential in the formation of certain amino acids and hormones. Infants with this disease show signs of mental retardation, poor motor development, poor growth, and seizures, although they do not show any symptoms for the first few months. Phenylketonuria is easily treatable with the proper dietary accommodations if it is diagnosed early enough.
  • Sickle cell disease, which is characterized by the malformation of red blood cells. Red blood cells carry oxygen throughout the body and normally have a donut shape when healthy. When a person has a sickle cell disease such as sickle cell anemia or sickle beta thalassemia, the red blood cells become crescent-shaped and hard. They then can clog up the arteries and impede the transport of oxygen, which can be not only dangerous---they can block important organs such as the spleen or the brain---but also very painful. If untreated, an infant will appear normal for the first few months, but then show signs of retarded growth and become more vulnerable to infection. If the disease is caught early and treated, the more severe symptoms can be avoided (see Section 2.1.5).
  • Cystic fibrosis, a disorder that causes excessive production of mucus. The mucus can damage organs and puts the patient particularly at risk for lung infection. Cystic fibrosis can be tested for in either the baby's genetic makeup or through a biomarker test measuring chemical immunoreactive trypsinogen (IRT). If the infant tests positive, the initial test will be followed up with a sweat test which measures the concentration of salt. If the diagnosis is confirmed, the infant may be treated with medications and chest therapy (see Section 2.1.2).

Hospitals may also include a variety of other newborn screenings as part of their newborn care protocol and state's requirements.

Presymptomatic testing

Not all disorders present symptoms early in life, so sometimes a patient will be get testing before symptoms present themselves. If a person has a sibling or parent with a disorder, they are especially good candidates for presymptomatic testing. A patient can receive preventive care or make life planning decisions based on the results of their test.

3.1.3 Potential Personal Impacts of Genetic Testing

There are both personal advantages and personal disadvantages to having your DNA tested.

Some positive outcomes from receiving genetic testing include that if the patient tests positive for a certain disorder, the patient (and the patient's family) can identify effective treatments, start treating the disorder earlier in the disease's development, and take more lifestyle precautionary measures. Acting early can help to preserve the patient's life, or at least ease symptoms. Testing can also reduce uncertainty. A diagnosis can make sense of already-expressed symptoms and help families make plans for the future. Also, if the testing comes back negative, it can give the patient and their family greater peace of mind.

However, there are also negative consequences of testing. Some people would rather not live their life dreading a future onset of Parkinson's, for example. Many genetic diseases do not have cures or even effective treatments yet, so the news that a patient has a disease can be very depressing for them. Also, a diagnosis does not tell a patient how severe a disorder will be, how soon the disease will present itself, or even determine with certainty that they will have symptoms---all of which can make planning difficult. In addition, insurance companies or employers might discriminate against a person if they know they are more likely to have medical problems in the future. Sometimes diagnoses can cause frustration or resentment toward the family member that passed on the gene, or guilt on the part of the parent that passed it on.

Most genetic tests do not carry inherent risks, although there is a slight risk of losing a pregnancy by conducting a prenatal sampling of amniotic fluid.

Sorting through the heap of benefits and negative consequences might require the help of a genetic counselor. Counseling and educational resources should be offered to patients trying to make testing decisions (see Section 4 on Genetic Counseling).

3.1.4 Ethical Considerations of Genetic Testing

In addition to the way that genetic testing can affect a person's life, it can also have an impact on society. It can be a slippery slope. If parents can choose from an assortment of embryos to pick one that doesn't have a life-threatening genetic mutation, they can also choose based on other genetic markers. It is becoming a reality with preimplementation genetic diagnosis that parents can pick an embryo for a certain gender, for a certain eye color, or for a child that can get freckles. To a degree, parents of the future could select embryos with genes that predict athletic ability or high intelligence, or other features they deem desirable.

There are many ethical objections to the expansion of embryonic selection. Some think that no one should have the power to "play God" and interfere with what has traditionally been seen as a process beyond our control. Others think it's wrong to choose a life path for another person before they are born. Others worry that such choosing power could push socio-economic classes further apart, creating a schism between those who can afford to select their children's traits and those who can't. Others worry that it might definitively label those with disabilities as inferior, unnecessary, or undesirable.

No one can forecast how having this sort of control over offspring could influence our society, and no one knows where to draw the line to keep ourselves as a human race within ethical bounds. While academics may continue to debate these issues, and more research may be conducted such that we have a better idea what we are getting into, the United State is not limiting embryonic selection and implantation to exclude selection of gender and other traits. While in some other countries in vitro fertilization is available only to infertile people or those who are likely to pass on a debilitating genetic disease, and with the selection of embryos based perceived embryo viability and on health considerations, this is not the case in the U.S.

3.2 Gene Therapy

3.2.1 What is Gene Therapy?

Gene therapy is a way to treat diseases by deleting or inserting new genetic material into cells. It is one of the newest branches of genomic medicine. Since the technology is still new and still requires extensive research to lower its associated risks, gene therapy is not yet widely available for human treatment.

Gene therapy can occur before a person is born or in fully developed people.

Germline gene therapy is when the editing of genes occurs to cells in the germline (the eggs, sperm, or embryo) before an individual is born. This type of therapy could help individuals who intend to have children to not pass on a genetic disease to subsequent generations. This type of therapy involves editing the germline cells outside of a person's body ("in vitro") and then inserting them back into the mother. The embryonic state is usually the best (and most common) time to cure a genetic disease, since the edited DNA will replicate itself into all of the individual's cells as the embryo grows into a fully-formed person. However, this type of therapy is barely beginning to be used in humans and only in highly-controlled research trials.

On the other hand, somatic gene therapy has been used in research trials over the past 20 years to treat fully-formed patients (not embryos) who have already developed a disease. This is called treatment "in vivo." By definition, somatic gene therapy targets any type of cell besides the sex cells. Individuals receiving somatic gene therapy can improve symptoms of a disease they have already been diagnosed with, but they are just as likely to pass on the disease to their children as they were before treatment.

Both types of gene therapy can use any of the following three general strategies:

  • knocking out mutated genes that cause a disease
  • replacing mutated genes with new, healthy genes
  • introducing new, non-naturally-occurring genes that will help to fight a disease.
Somatic vs Germline gene editing
Somatic gene editing compared to germline gene editing.
Figure 3.1

3.2.2 Emerging Therapies and Their Risks

How can you change DNA that is already in a cell? Scientists have discovered a variety of ways:

One of the first (and still most common) strategies to insert new DNA into an individual uses viral vectors. Viruses already have the natural ability to inject their RNA into cells and replicate themselves. So, scientists capitalize on this ability by inserting healthy genes into synthetic viruses, removing the part of the viruses that could make someone sick, and then injecting the virus either into a diseased person or an embryo. The virus does what viruses do and injects the customized DNA into the cells of its host.

Depending on the intent of the treatment, the inserted DNA might create a protein that disrupts a mutated gene, causing it to stop its destructive function. Or, the new DNA sequences might code for healthy proteins that the individual could not previously make.

A new gene is inserted directly into a cell. A carrier called a vector is genetically engineered to deliver the gene. An adenovirus introduces the DNA into the nucleus of the cell, but the DNA is not integrated into a chromosome.
A new gene is inserted directly into a cell. A carrier called a vector is genetically engineered to deliver the gene. An adenovirus introduces the DNA into the nucleus of the cell, but the DNA is not integrated into a chromosome.
Figure 3.2

So far, viral vectors are the most successful gene therapy technique we have, especially for in vivo treatments. However, viral vectors come with an array of risks---a dramatic immunoresponse can cause inflammation and even organ failure. Also, the inserted virus could disrupt the wrong gene. In some cases, people have died as the result of the injection of a viral vector that was intended to cure their genetic disease. Also, there are only a few functional types of viral vectors, and if a person's body develops immunity to a certain type, that person can never use that type of vector again.

Alternative methods provide possible solutions to these problems. For example, one of the most exciting discoveries is CRISPR technology. This technology allows gene editors to cut the genome at a specific place---say, in the middle of a gene that was causing a disease---and in some cases even to insert a more desirable gene sequence in its place.

CRISPR was first discovered in bacteria, which use CRISPR plus an enzyme called Cas9 to fight viruses. CRISPR stands for "clustered regularly interspaced short palindromic repeats", a description of a type of pattern found in bacterial DNA. This pattern is made up of repeating nucleotides interspersed with short "spacers."

Bacteria acquire these short "spacer" patterns in their DNA when they encounter a new virus. The spacer sequence is actually a replica of a small portion of the virus's DNA that the bacteria has incorporated into its own sequence. Keeping this replicated sequence in their genome allows the bacteria to quickly recognize a virus if it encounters it again.

To destroy the virus, the bacteria transcribes the spacer bit of its DNA into RNA (this piece of RNA is called "guide RNA") and attaches an enzyme called Cas9 to the guide RNA. Cas9 can chop up viruses. The guide RNA can then go off in search of the virus. Once the guide RNA recognizes the virus by binding its sequence to the matching sequence on the virus's DNA, it triggers the function of Cas9, and the virus is subsequently chopped into pieces. Threat eliminated.

Using the same strategy, scientists can disrupt a gene (in an embryo, a plant, an animal, or even a fully formed human) by creating a bacterial cell with a section of DNA sequence that matches the sequence they want to disrupt.

In the most basic form of CRISPR, Cas9 will simply cut the bad gene and disable it. Even though the DNA will repair itself, cuts that have "blunt ends", meaning the DNA was cut in the same place on both strands, tend to have more messy repairs. This means that the bad gene will likely be poorly repaired and be permanently disabled.

What is great about CRISPR is that the guide RNA can attach to more enzymes besides just Cas9, allowing a wide range of treatment possibilities. Some have compared CRISPR to a Swiss army knife because it can be used in so many different capacities. Scientists have found ways to attach other molecules. One attachment is an enzyme that cuts the two strands of DNA at slightly different locations, giving the ends an overhang that allows new DNA sequences to be inserted. This makes possible the removal and replacement of single nucleotides, like "fixing a typo" in the genetic sequence.

The versatility of CRISPR makes it one of the most promising genetic editing tools available. However, it is still very new. In fact, CRISPR-Cas9 was inserted directly into a human body for the first time in 2020. Other data has been recently released regarding the use of CRISPR in editing human embryos. Unfortunately, the research showed some serious safety concerns.

These concerns reemphasized that CRISPR comes with its own set of problems. One problem is that it is not nearly as easy to deliver CRISPR to mature cells as it is with viral vectors, meaning it is a less effective tool for in vivo treatment. Also, like viral vectors, it is still not always effective even when it is inserted into cells, and sometimes can even edit the wrong gene, causing complications. Much more research and development is needed before this technology can be widely used in humans, either in vivo or in vitro.

There are other techniques similar to CRISPR, such as ZFNs (Zinc Finger Nucleases) and TALENs (Transcription activator-like effector nucleases), but since CRISPR is newer and more efficient, we won't delve deeply into those other techniques in this course.

3.2.3 Ethical Considerations of Gene Editing

Although human embryo editing is relatively easy to achieve, it is difficult to do well and with responsibility for lifelong health outcomes.

~Jennifer Doudna (Nobel-prize-winning biochemist, pioneer of CRISPR-mediated genomic editing)

As Jennifer Doudna said, genomic editing comes with enormous responsibilities. Although this type of editing could cure life-altering diseases and be a great source of good, it could also to be used to change traits such as appearance, athleticism, intelligence, or other non-necessary attributes. The risks of runaway gene editing are similar to the concerns about selecting embryos mentioned in Section 3.1.4.

However, gene editing, especially germline gene editing, has even more weighty risks than embryonic selection. In embryonic selection, genes still recombine as mostly whole units, in their naturally occurring states, and then scientists select from those natural states. But in both somatic and germline gene editing, scientists actually modify the genes themselves. This raises concerns given how little we know about the human genome and our inability to predict downstream consequences of altering any given gene. Trying to cure one disease might even cause another. With germline editing, any alterations are heritable, and thus will be passed on to any future generations.

After Dr. He Jiankui announced the birth of two girls whose genes he and his team had edited, using CRISPR technology in 2018, scientific communities have been debating a global moratorium on human germline editing to make genetically modified children. It is a difficult path to gain international agreement to establish an framework and conditions for altering the human genome for clinical uses. To date, such a moratorium does not exist.

3.4 Impact of Genomic Medicine on Healthcare

Genomic medicine is revolutionizing the healthcare industry by helping patients find more effective treatments more quickly, whether through sequencing their genomes to provide diagnoses, more specialized treatment, or even through gene therapy. Much of technology in the field of genomic medicine is in its beginning stages, but as the bank of research continues to expand, more diseases will be able to be treated in more efficient ways.

4 Genetic Counseling

A doctor can order genetic tests for a patient, but some doctors are not trained on how to interpret test results or how to help a patient navigate the results. That is the role of a genetic counselor. Genetic counselors have graduate degree training in both genetics and counseling. Genetic counseling is for those who are wondering if they or a loved one are at risk for a disease, for those who have already received a diagnosis, or for those looking at the risk of having children with a disease.

4.1 Roles of Genetic Counselors

4.1.1 Gather Family Medical History

You can gain a lot of insight about a person's genetics without sequencing a single gene---just look at a family tree. A genetic counselor will help a patient go through their family tree and help them systematically note what diseases or conditions each of their relatives have had. The patient might need to call up other relatives to see what they know about other people in the family. Then, the counselor can help the patient see patterns and make basic predictions about how some traits might have been passed on to them or on to their children.

4.1.2 Genetic Testing and Interpretation

A genetic counselor or a doctor can request sequencing testing, either for the whole genome or for specific genes. After a patient has received their DNA sequencing results, genetic counselors have the expertise to look at the sequence data and interpret the risk of disease.

4.1.3 Advisement on Medical Treatment

Based on the results from the sequencing and family history assessment, the genetic counselor can provide information about the results and provide emotional support to help individuals make decisions on treatment options, therapies, and lifestyle changes to help improve quality of life. In contrast, a medical geneticist is a licensed physician who has undergone additional special training to diagnose and treat patients with hereditary disorders.

More Knowledge, Clearer Decisions: A Case Study

At 40, I had twins, and one of the twins has Down syndrome. My husband and I wanted to have another child two years later, so we went to a genetic counselor to find out whether if we had another baby, if that baby would have Down syndrome too. The genetic counselor reviewed our family histories with us, mapping them out on paper and discussing all the details. Getting into the details with a counselor made us feel better—with more knowledge, I felt we could make a better decision. I also loved that she didn’t pressure us to make a decision either way. Her help gave us confidence to face our future decision about having another child.

Cindy C., Utah, parent of child with Down syndrome

4.1.4 Advisement on Family Planning

If a patient is considering starting a family, genetic tests and family history can also shed light on which alleles the patient could pass on to their children. It is important both partners get their genes sequenced to get a more accurate picture the future child's risk. A genetic counselor can walk the patient through the probability of having children with a disease and help them to consider when/if/how many children to have.

A counselor can also educate a patient on the costs, risks, and benefits of in vitro fertilization or adoption if natural conception seems too risky or not possible.

In cases where a pregnant woman is having her fetus's genome sequenced, a counselor can inform the couple whether baby will be born with a certain disease. The counselor can also help the couple prepare to care for a child with a disease if they choose to bring the pregnancy to term.

4.1.5 Emotional Support

Given the intense and complicated emotions and decisions that come with a diagnosis of a patient or their loved one (also discussed in Sections 3.1.3 and 3.1.4), a counselor can help them process and manage their feelings. In addition to medical genetics, genetic counselors have received training in bioethics, psychosocial counseling, and patient advocacy as a part of their academic and clinical training.

5 Nursing Roles: Patient Support

5.1 Providing Support to Patients and Loved Ones

As a nurse, it is important to report any emotional needs of the patient or their loved ones to the doctor and applicable members of their care management team. Given the close interaction, nurses can ascertain if both the patient and their loved ones are coping well, and can take note of their affect and their willingness to communicate. Understanding of how the patient or their loved ones are doing emotionally, can help the care management to line up resources for the patient and their loved ones and make them aware of resources that are available both in a medical setting and in their community.

The patient's loved ones may need just as much or more emotional support than the patient. Sometimes simply being with the patient and their loved ones with a willingness to listen and acknowledging their efforts and support of each other, can go a long way.

If the patient receives a diagnosis, it will also likely be a nurse's responsibility to help educate patients and their loved ones about the disease and inform them of how the different members of their healthcare team can advocate for them. Feeling more educated and supported can help combat fear and uncertainty. This can be a great help not just to the patients and their families, but also to those you work with.

5.2 Support Groups

Being able to talk to others who understand can be an enormous mental and emotional aid. It can also help the patient learn about specialists or new potential treatments or research trials. If a patient or family member is open to considering a support group, you can introduce them to the appropriate social worker or care management specialist within your organization, if available. Patients can try contacting their health insurance provider for suggestions. The National Organization of Rare Diseases maintains a listing of organizations that provide assistance to patients and families affected by rare diseases. (

Since the organizations list is extensive, it is easier to use the search field for their rare disease database. Once within a disease-specific page, scroll to the bottom of the entry (just above "References") to find organizations. (

6 Participating in Research Trials

Given the limited available options for treatment of genetic disorders, a patient with a genetic disorder may want to consider a clinical research trial. It is likely that patients have heard of clinical trials or have at least seen recruiting information about them.

Before any kind of medical indication such as a medication, procedure, medical device, or testing method can become standard and help people on a wide scale, it has to go through a rigorous testing process that includes multiple rounds of clinical research trials.

The NIH definition of a clinical trial is: A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

Clinical trial decision tree
Source: NIH
Figure 6.1

Clinical trials in particular are a kind of clinical research designed to evaluate and test new interventions such as psychotherapy or medications.

Patients may not be aware of the different types of clinical research that researchers use depending on what they are studying. The FDA identifies the following categories:

Treatment Research generally involves an intervention such as medication, psychotherapy, new devices, or new approaches to surgery or radiation therapy.

Prevention Research looks for better ways to prevent disorders from developing or returning. Different kinds of prevention research may study medicines, vitamins, vaccines, minerals, or lifestyle changes.

Diagnostic Research refers to the practice of looking for better ways to identify a particular disorder or condition.

Screening Research aims to find the best ways to detect certain disorders or health conditions.

Quality of Life Research explores ways to improve comfort and the quality of life for individuals with a chronic illness.

Genetic studies aim to improve the prediction of disorders by identifying and understanding how genes and illnesses may be related. Research in this area may explore ways in which a person's genes make him or her more or less likely to develop a disorder. This may lead to development of tailor-made treatments based on a patient's genetic make-up.

Epidemiological studies seek to identify the patterns, causes, and control of disorders in groups of people

When clinical research is used to evaluate medications and devices clinical trials are conducted.

For a treatment to move along in the clinical research process, volunteers are needed. Many trials have to end early because they don't have enough participants, so clinical researchers are always looking for more patients to participate. Research trials need both healthy participants and participants with specified conditions.

When research involves rare genetic diseases, the pool of potential participants can be quite small. The principal investigator (PI), often a physician, is responsible and accountable for the research, including selecting qualified team members to run the trial, and protecting the safety, and welfare of the participants. As such, nurses often participate as team members, including assisting with collecting data of prospective trial participants that will be evaluated for fit.

This can involve:

  • Examining the patient and taking vitals
  • Asking about the patient's medical history
  • Checking for concomitant medications
  • Administering study questionnaires
  • Asking about any adverse events since the last checkup
  • Administering medications or other shots
  • Drawing blood or collecting other types of samples for testing.
  • Referring the patient to get an electrocardiogram, MRI, or ultrasound.

Depending on roles and staffing at a facility nurses may help to coordinate travel or other logistics for the patient.

Nurses can also serve as principal investigators in clinical trials. As with any non-physician PI, a physician will need to be a sub-investigator (or a dentist depending upon the trial).

6.1 Risks and Rewards

Because the treatments in a clinical research trial are not yet proven to be safe or effective for humans, anyone who participates in a research trial assumes some risk. Participating in a trial could result in no improvement, further health issues, or in rare cases death. In addition, participating in a trial requires a patient giving up some conveniences---they must either live close or be able to regularly travel to the participating trial site. They often cannot leave for extended vacations. Sometimes the data collection process is unpleasant. However, it is important to remember that any medical treatment comes with some inconvenience and risk. The patient needs to determine whether the cost is worth the reward. For instance, a patient with a terminal illness might feel as though they have nothing to lose and everything to gain, and they might be very willing to participate in a study. Another patient with a mild illness might be more hesitant to sign up for a trial that might potentially lessen their quality of life.

Research studies make it easy to know what the risks and rewards are. Before any patient enrolls in a trial and becomes a subject/participant, they will have to provide informed consent. They will be given an informed consent document. The informed consent document is usually written for an 8th-grade reading level and explains the basic objectives and structure of the study. It will let the patient know what will be required of them to participate, the length of the study, potential risks and benefits, and other information the patient would need to make the best decision for themselves. Aside from the document, the consent process needs to include an adequate opportunity for the patient to ask questions and receive explanations from people who have the knowledge to provide accurate replies. Informed consent is normally considered an ongoing process and exchange of information with the participant and team throughout the clinical investigation, and not just leading up to the signing of a consent form.

Although risks are involved, the patient can be comforted by knowing that any federally approved trial will have been reviewed by an Institutional Review Board (IRB) which determines that the trial is ethical and safe enough to attempt. No trial will move forward unless the researchers can prove that there is good evidence that the treatment will work in humans. Before a clinical trial, the researchers must show that the treatment works in non-human trials (called "pre-clinical trials").

The benefits of participating in a study can be enormous. Sometimes the treatment in a study can work better than the current standard treatment practice. The trial participant may gain access to cutting-edge treatment and be reimbursed for associated expenses. Some genetic diseases do not have approved treatments, and the only hope a patient has for treatment could be participating in a study. Also, whether a patient participates in a trial to test a medication, a procedure, a device, or a better way of testing, they are helping further the field of medicine and benefitting all of the people that share their disease. Some clinical trials also offer payment to participants, as a recruitment incentive.

6.2 Structure of Clinical Trials

Here is a brief description of how a clinical trial is set up. Each clinical trial is split up into parts called "phases." Each phase has a different purpose and help scientists answer different questions. Phase numbers may be written in Roman numerals (I, II, III, IV) or Arabic numerals (1,2,3,4).

In Phase 1, researchers work with a small number of volunteers, typically 80 or fewer, with the purpose of evaluating safety and dosage. Often this is done with healthy volunteers, and/or with cancer patients if a drug's intended use is for cancer. In this phase researchers are determining how much of a drug can be tolerated and what the side effects are with different dosing schemes. You may sometimes hear of a phase 0. In 2006 FDA added a phase 0 and then later rolled it to the early part of a phase 1 for investigational drugs. The intent is to bridge the gap between pre-clinical and clinical trials with its short duration (less than a week) and fewer than 20 subjects to provide preliminary information about a drug's pharmacokinetics, mechanism of action, and pharmacodynamics, within in the target population using microdosing for subtherapeutic exposure.

According to the FDA, 70% of drugs in Phase 1 trials move on to Phase 2.

Phase 2 targets a larger number of people with the disease or condition, typically a few hundred people. This phase can last up to two years and is used to collect additional safety data and refine research questions and methods. Since there only several hundred participants, there is not enough information to show how beneficial a drug will be. From the Phase 2 information and analysis, researchers can design a Phase 3. Only one third of drugs will move on to a Phase 3.

Phase 3 trials can last up to four years with up to several thousand people who have the condition or disease. This is the last phase prior to FDA approval. Because of the larger size and duration of the study, researchers can further evaluate the safety, and efficacy, and have a better chance of seeing uncommon and long-term side effects. Twenty-five to thirty percent of drugs move on to the next phase.

Phase 4 trials, also referred to as post-marketing studies, are carried out with several thousand volunteers with the disease or condition after a treatment has been approved for use by the FDA. This phase provides additional information including risks, benefits and best use.

If a patient is enrolled in a clinical research study, they may not be told if they are receiving the treatment being tested. As the NIH notes on their website, "In many trials, no one---not even the research team---knows who gets the treatment, the placebo, or another intervention. When participants, family members, and staff all are "blind" to the treatment while the study is underway, the study is called a "double-blind, placebo-controlled" clinical trial."

6.3 Enrolling in a Trial

There are many support groups and websites that help patients find clinical trials, generally speaking, but finding a good match for specific genetic disorders can be difficult. If a patient wants to be part of an ongoing trial, they will need to travel or move to a participating facility which is also called a clinical trial site or an investigator site, or you can check to see if your facility can apply to participate in a trial. Normally, for trials, hospitals are recruited more often than patients directly. Researchers reach out to hospitals that already have patients with the disease being studied and ask them to invite their patients to participate. However, patients can also self-refer. Two websites to look for clinical trials are: ( (

Aside from the aforementioned informed consent, before a patient can be enrolled in a trial, they must meet the eligibility requirements and pass a screening, which may include bloodwork, a physical exam, or other tests.

6.4 Resources

National Human Genome Research Institute - Genetic Disorders

A listing of genetic diseases and educational materials including a glossary of genetic terms

National Human Genome Research Institute -- Genetic and Rare Diseases Information Center (GARD)

"GARD provides immediate, virtually round-the-clock access to experienced information specialists who can furnish current and accurate information - in both English and Spanish - about genetic and rare diseases."

The National Organization of Rare Diseases (NORD).

NORD maintains a listing of organizations that provide assistance to patients and families affected by rare diseases.


Both sites aggregate information about clinical trials.

ISONG International Society of Nurses in Genetics

Headquartered in Pennsylvania, this organization is "Dedicated to fostering the scientific and professional growth of nurses in human genetics and genomics worldwide."


Amino acids
The building blocks of protein
Carrier testing
Genetic testing used to determine if an individual is a carrier of an allele that might be passed on to offspring, potentially causing the offspring to develop a genetic disorder.
One of the two halves that comprise a chromosome. Our sex cells contain one chromatid from each type of chromosome.
Tightly-wound, discrete units of DNA that contain many genes. Each type chromosome comes in a pair. Humans have 23 sets of chromosomes.
Clinical research trials
A type of research that uses humans as subjects.
A 3-nucleotide segment of RNA or DNA that codes for an amino acid.
A gene editing method that can target specific genetic sequences and cut them.
Diagnostic genetic testing
Genetic testing used to confirm or rule out if a patient has a genetic disorder.
A molecule that stores genetic information about how your body should develop and function
Dominant allele
The version of a gene that, if present, will mask the other version of the gene on the complementary chromosome.
A fertilized egg, the product of a joined sperm and egg.
When a gene is turned on
A distinct segment of DNA that contains nucleotides that contribute to a particular trait.
Gene expression
The body's way of controlling which genes are active in which cells.
Gene therapy
A way to treat diseases by inserting or deleting new genes into cells.
Genetic counselor
An individual with graduate training in both genetics and counseling who can help patients gather and interpret genetic data, as well as help them navigate their decisions and the emotional impact of dealing with genetic disorders.
Genetic disorder
A health condition because of an inherited mutation that causes significant problems.
The entire set of chromosomes in an organism.
Genomic medicine
A subspecialty of precision medicine in which a patient's genetic information is used to determine the type of clinical care they will receive.
Germline gene therapy
A type of gene therapy involving the editing of genes in the germline (the eggs, sperm, or embryo) before an individual is born.
Informed consent
A process used to communicate between the research institution, the doctor and the patient interested in participating in a clinical trial. The informed consent document describes what will be required of the patient to participate, the length of the study, potential risks, and all of the other info the patient would need to make the best decision for themselves.
Investigator site
A hospital or other location where a clinical research trial is conducted.
The cell division of germ cells through which the body creates sex cells.
Structures inside the cell that produce the cell's energy.
An alteration in a DNA sequence
Newborn screening
Testing of newborns to try to detect genetic disorders as early as possible. Abnormal screens are much more common than diagnosed core disorders. For example, Texas Health and Human Services notes that 1 in 40 screens indicate an abnormal result, yet of all births, fewer than 1 in 400 will end up having a core disorder diagnosed.
Small units that comprise DNA. They encode information based on their order in the DNA strand.
Precision medicine
The tailoring of a patient's treatment and prevention of disease based on the patient's lifestyle, environment, biomarkers, and genetic makeup.
Preimplantation testing
Genetic testing of embryos fertilized in vitro to make sure they do not have a particular allele before implanting them into the uterus.
Prenatal testing
Genetic testing of fetus DNA before birth, often collected through a sample of amniotic fluid from the mother.
Presymptomatic testing
Genetic testing of individuals who are at risk for developing a genetic disorder but do not yet show symptoms.
Polygenic trait
a phenotype that is influenced by more than one gene.
Recessive allele
The version of a gene that, in the presence of a dominant allele, will not be expressed. Two recessive alleles are needed for a recessive trait to be expressed.
When a gene is turned off.
A molecule that attaches to a gene to turn it off
Ribonucleic acid (RNA) is intermediary molecule between DNA and protein. RNA is transcribed from DNA and then is translated into amino acids, which form protein.
Sex cells
The cells the body uses to reproduce, also known as gametes. Female sex cells are called eggs or ova, male sex cells are called sperm.
Somatic gene therapy
A type of gene therapy involving the editing of genes in somatic (non-sex) cells.
The process through which DNA is converted into RNA.
The process in which RNA codes for amino acids, which form protein.
Viral vectors
A type of gene edited virus that is used to inject edited DNA into a host.


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