genome

Genes are sections of DNA in your cells that are passed down (inherited) from your parents. You inherit two copies of each gene, one from each parent. Genes carry information that controls what you look like and how your body works.

There are about 20,000 genes that provide instructions for making proteins, which your body needs to work correctly.

Some genes don't make proteins themselves but instead help control how other genes work. They act like switches, turning other genes on or off. This means they help decide when, where, and how much of a protein is made in your body.

Changes in your genes are also called gene variants or mutations. These changes can be inherited, occur as you age, or result from environmental factors such as chemicals or radiation. Often, these changes have no effect, but sometimes, even a small change in the DNA can alter the instructions for making proteins. If genes don't make the right proteins, or don't make them correctly, this can cause a genetic disorder.

Gene therapy uses genes to treat or prevent disease by correcting genetic problems. It works by changing your genetic material, rather than relying on traditional treatments like medicine or surgery.

New genetic material can be delivered into cells in two main ways:

• ex-vivo treatment. Cells are removed from your body, modified by adding genetic material, and then placed back into your body.
• in-vivo treatment. Genetic material is delivered directly into your body, often through an injection.

A common form of gene therapy involves inserting a normal gene to replace an abnormal gene. Other approaches include:

• Repairing an abnormal gene
• Altering the degree to which a gene is turned on or off

Newer techniques offer different ways to correct genetic problems:

• Genome editing (also called gene editing). Instead of adding new genetic material into cells, this approach changes the DNA that's already in your cells. A well-known example is CRISPR-Cas9. This promising technique is still being studied and may soon be used to treat genetic disorders.
• Cell-based gene therapy combines gene therapy and cell therapy. An example of this would be CAR T cell therapy. Cells, which are often immune system cells, are genetically altered to help treat a disease and then introduced into the body.

Gene therapies are currently only approved to treat a small number of diseases, such as:

• Leber congenital amaurosis, an inherited eye disorder.
• Spinal muscular atrophy, a genetic muscle disorder.

While gene therapy holds great promise, it comes with risks and challenges. Studies are still ongoing to ensure these treatments are safe and effective. Some challenges include:

• Immune system reactions. Your body may see the new material as a threat and react to it.
• Unintended effects. Changes to DNA could affect other genes in harmful ways.
• High costs. Gene therapies are often expensive and are not widely accessible.

Genetic disorders are health conditions caused by changes (also called mutations or variants) in your genes. Genes are parts of DNA found in your cells that carry instructions for how your body grows, develops, and functions. Many genes tell your body how to make proteins, which are needed for your body to work properly.

A genetic disorder happens when a gene variant changes how a protein is made. The variant may cause the protein to work poorly or not be made at all. If genes don't make the right proteins, or don't make them correctly, it can lead to a genetic disorder.

Not all gene changes cause disease. Often, these changes have no effect. But sometimes, even a small change in DNA can affect how proteins are made.

Gene variants can be grouped into two main types:

• Inherited variants (also called germline variants) are passed down from your parents. They come from egg or sperm cells.
• Non-inherited (also called somatic variants) are not passed down from your parents. They happen during your lifetime. They may be caused by things like harmful chemicals or ultraviolet (UV) rays from the sun.

Genetic disorders may be caused by:

• Single gene disorders are caused by changes in one gene. Examples can include sickle cell anemia, where a change in a single gene can cause the condition, and Charcot-Marie-Tooth disease, where a variant in one of many different genes can cause the condition.
• Chromosomal disorders are caused by missing, extra, or altered chromosomes. Chromosomes are structures that carry genes. These disorders involve changes in the number of chromosomes people have or changes in the structure of one or more chromosomes. An example is Down syndrome, which is caused by an extra copy of chromosome 21.
• Complex (multifactorial) disorders are caused by changes in many genes. Each change alone may not cause the disease, but together they increase the risk. Lifestyle and environmental factors, such as exercise, diet, or exposure to pollutants, also play a role. Colon cancer is an example.

Some genetic conditions are passed down through families (inherited) in one of several patterns, depending on the specific gene involved.

Patterns of inheritance can include:

• Dominant means you only need one changed gene to cause the condition.
• Recessive means you need two changed copies of the gene (one from each parent) for the condition to occur.
• X-linked conditions involve genes located on the X chromosome. These conditions often affect males more frequently.
• Mitochondrial conditions are passed down by the mother.

Your health care provider may check for a genetic condition based on:

• A physical examination.
• Your personal medical history.
• Your family health history.
• Laboratory tests, including genetic testing.

NIH: National Library of Medicine

Genetic testing is a type of medical test that looks for changes, sometimes called variants or mutations, in your DNA. DNA contains the genetic instructions in all living things. Often, these changes have no effect, but sometimes, even a small change in DNA can cause disease or other health conditions.

Genetic tests take a sample of your blood or tissues and check your cells to look for any changes in:

• Genes are parts of DNA found in your cells that carry information that controls what you look like and how your body works. Many genes tell your body how to make proteins, which are needed for your body to work correctly.
  • Genome sequencing is a process that checks all your DNA.
  • Exome sequencing is a process that only checks the parts of your DNA that provide instructions to make proteins.
• Proteins do most of the work in your cells. If there are changes in the amount and activity level of proteins, they might be due to changes in the genes that produce those proteins.
• Chromosomes are thread-like structures in your cells. Each chromosome is made up of DNA tightly packaged around proteins. People usually have 23 pairs of chromosomes that contain all their DNA.

Most of the time, genetic testing is done through your health care provider. This is called clinical testing. It is done to find out about an inherited disorder (passed down through families) and to help make decisions about your care.

Other ways to get genetic testing include:

• Research-based testing is a genetic test done as part of a research study (clinical trial).
• Direct-to-consumer (DTC) testing is a genetic test that allows you to send a DNA sample and get the results. You may do this to learn about your ancestry or your risk for certain diseases.

Genetic testing may be done for many different reasons, including to:

• Find genetic diseases in a fetus. This is a type of prenatal testing.
• Screen newborn babies for certain treatable conditions.
• Lower the risk of genetic diseases in embryos that were created using assisted reproductive technology.
• Find out if you carry a gene for a certain disease that could be passed on to your children. This is called carrier testing.
• See whether you are at an increased risk of getting a specific disease. This may be done for a disease that runs in your family.
• Diagnose certain diseases.
• Identify genetic changes that may be causing or contributing to a disease that you were already diagnosed with.
• Help guide your provider in deciding the best medicine and dosage for you. This is called pharmacogenomic testing.
• To check for, monitor, or manage a disease. This is sometimes used to help find the best cancer treatment.
• To confirm the biological father (paternity) of a child, or how much genetic information is shared with other relatives.
• To explore the likelihood of having or developing certain physical traits, such as hair color or facial dimples, or to learn about your ancestry.
• To help advance our understanding of genetic conditions, learn how genes work, and find unknown genes.

Genetic tests are often done on a blood or cheek swab sample. But they may also be done on samples of hair, saliva, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. The sample is sent to a laboratory. There, a lab technician will use one of several different techniques to look for genetic changes.

The benefits of genetic testing include:

• Helping your provider make recommendations for the management or monitoring of a genetic condition.
• Giving you more information for making decisions about your health and your family's health:
  • If you find out that you are at risk for a certain disease, you might take steps to lower that risk. For example, you may find out that you should be screened for a disease earlier and more often. Or you might decide to make healthy lifestyle changes.
  • If you find out that you are not at risk for a certain disease, then you can talk to your provider about when it would be appropriate to schedule checkups or screenings.
  • A test could give you information that helps you make decisions about having children.
• Identifying genetic disorders early in life so that treatment can start as soon as possible.

The physical risks of the different types of genetic testing are small. But there can be emotional, social, or financial drawbacks:

• Depending on the results, you may feel angry, depressed, anxious, or guilty. This can be especially true if you are diagnosed with a disease that does not have effective treatments.
• Despite the protections that are in place, you may be worried about genetic discrimination in employment or insurance.
• Genetic testing may give you limited information about a genetic disease. For example, it cannot tell you whether you will have symptoms, how severe a disease might be, or whether a disease will get worse over time.
• Genetic testing results might be inconclusive. For example, you might keep getting negative results or not get an answer at all.
• Some genetic tests may give you results that you didn't expect. For example, if you are tested to check for the cause of a rare disease, and a different variant is found that puts you at increased risk for something else that was previously unknown.
• Some genetic tests are expensive, and health insurance might only cover part of the cost. Or they may not cover it at all.

The decision about whether to have genetic testing is complex. In addition to discussing the test with your provider, you can meet with a genetic counselor. Genetic counselors have specialized degrees and experience in genetics and counseling. They can help you understand the tests and weigh the risks and benefits. If you do take a test, they can explain the results and make sure that you have the support that you need.

Cloning describes the processes used to create an exact genetic replica of another cell, tissue or organism. The copied material, which has the same genetic makeup as the original, is referred to as a clone. The most famous clone was a Scottish sheep named Dolly.

There are three different types of cloning:

• Gene cloning, which creates copies of genes or segments of DNA
• Reproductive cloning, which creates copies of whole animals
• Therapeutic cloning, which creates embryonic stem cells. Researchers hope to use these cells to grow healthy tissue to replace injured or diseased tissues in the human body.

NIH: National Human Genome Research Institute

Your family history includes health information about you and your close relatives. Families have many factors in common, including their genes, environment, and lifestyle. Looking at these factors can help you figure out whether you have a higher risk for certain health problems, such as heart disease, stroke, and cancer.

Having a family member with a disease raises your risk, but it does not mean that you will definitely get it. Knowing that you are at risk gives you a chance to reduce that risk by following a healthier lifestyle and getting tested as needed.

You can get started by talking to your relatives about their health. Draw a family tree and add the health information. Having copies of medical records and death certificates is also helpful.

Centers for Disease Control and Prevention

Genetic counseling provides information and support to people who have, or may be at risk for, genetic disorders. A genetic counselor meets with you to discuss genetic risks. The counseling may be for yourself or a family member. Or you may get it when you are planning or expecting a baby. You may follow up with genetic testing.

There are many reasons to seek genetic counseling. You may consider it if you :

• Have a personal or family history of a genetic condition or birth defect
• Are pregnant or planning to be pregnant after age 35
• Already have a child with a genetic disorder or birth defect
• Have had two or more pregnancy losses or a baby who died
• Have had ultrasound or screening tests that suggest a possible problem

Your newborn infant has screening tests before leaving the hospital. There may be different tests depending on the state where you live. They include:

• Tests on a few drops of blood from pricking the baby's heel. The tests look for inherited disorders. All states test for at least 30 of these conditions.
• A hearing test that measures the baby's response to sound
• A skin test that measures the level of oxygen in the blood. This can tell if the baby has a congenital heart defect.

These tests look for serious medical conditions. If not treated, some of these conditions can cause lifelong health problems. Others can cause early death. With early diagnosis, treatment can begin right away, before serious problems can occur or become permanent.

If a screening shows that your baby might have a condition, the health care provider or the state health department will call you. It is important to follow up quickly. Further testing can verify whether your baby has the condition. If so, treatment should start right away.

NIH: National Institute of Child Health and Human Development

A rare disease is one that affects fewer than 200,000 people in the United States. There are nearly 7,000 rare diseases. More than 25 million Americans have one.

Rare diseases:

• May involve chronic illness, disability, and often premature death
• Often have no treatment or not very effective treatment
• Are frequently not diagnosed correctly
• Are often very complex
• Are often caused by changes in genes

It can be hard to find a specialist who knows how to treat your rare disease. Disease advocacy groups, rare disease organizations, and genetics clinics may help you to find one.

NIH: National Institutes of Health

Almost every day, new findings from medical research are published in scientific journals. These journal articles often become sources for news stories. They can be important tools in helping you manage your health. But it's not always easy to understand them and know what they mean for your life. For example:

• What you hear about a study may not explain how it fits into the bigger picture.
• Sometimes the results of one study seem to disagree with the results of another study. That could be because the studies could have different designs and asked different questions. The news stories don't always explain this.
• Sometimes the studies are very small, and researchers need to do more studies to confirm the results. But the news stories about these small studies may not highlight this.

So it's important to think carefully when reading or listening to reports of new medical findings. Here are some questions that can help you evaluate that information:

• Was the study in animals or humans? Getting certain results in animals may not mean that you get those same results in humans.
• Were the people in the study similar to you in ways that may matter, such as age, race, or sex?
• How big was the study? Larger studies may get more reliable results than smaller studies.
• How long did the study last? For example, studies testing medicines need to be long enough to show long-term benefits or risks.
• What kind of study was it? Clinical trials, especially randomized controlled trials, give the clearest information about whether a treatment is effective and safe in humans. In randomized controlled trials, the people in the study are randomly divided into separate groups that get different treatments. This helps prevent bias in the results.
• Where was the research done?
• If a new treatment was being tested, what were the side effects? How common were they?
• How do the results from the study compare with previous studies? If the new study had different results, then more studies would be needed to confirm these results.
• Who paid for the research? Sometimes the people paying for the research could profit financially if the study gets certain results.
• Who is reporting the results? Do they have a certain bias?

It can be helpful to stay informed about new medical findings. But it's good to have some skepticism. Keep these questions in mind the next time you hear about a big new medical breakthrough.

Alpha-1 antitrypsin deficiency (AAT deficiency, or AATD) is an inherited condition that raises your risk for lung and liver disease. If you have this condition, your body doesn't make enough alpha-1 antitrypsin (AAT).

AAT is made by your liver. It helps protect your lungs from inflammation and irritating substances you might breathe in, such as smoke. If your liver doesn't make enough AAT, your lungs may be more easily damaged from smoking, pollution, or dust from the environment. This can lead to a serious lung condition called chronic obstructive pulmonary disease (COPD). AAT deficiency may also cause a liver disease called cirrhosis. This is more common in children who have AAT deficiency.

AAT deficiency is a genetic disorder. That means it's caused by changes in your genes, which may also be called gene variants or mutations.

Your genes carry information that controls what you look like and how your body works. AAT deficiency is caused by changes in the SERPINA1 gene, which carries instructions for making the AAT protein. These gene changes are inherited from your parents, so AAT deficiency tends to run in families:

• If you have two mutated copies of the gene, it means you have a condition called AAT deficiency. People with this disorder have a higher risk of getting lung disease or liver damage before the age of 45.
• If you have one mutated copy of the gene, you are a carrier of AAT deficiency. In these cases, this means you are at slightly higher risk of developing lung disease, especially if you have other risk factors, such as being a smoker. You could still pass the mutated gene on to your children.

There are a few gene changes that cause AAT deficiency. These gene changes can:

• Decrease the amount of AAT protein your liver makes.
• Prevent your liver from making any AAT.
• Affect the shape of the AAT protein so that it can't move out of your liver to protect your lungs. Over time, AAT builds up in your liver and causes damage.

Some people who have AAT deficiency do not have any symptoms. For those who do, symptoms usually appear in people between 20 and 50 years old. These symptoms may include:

• Wheezing
• Shortness of breath, especially after exercise
• Chronic cough with phlegm (mucus)
• Repeated respiratory infections such as colds and the flu
• Chest pain
• Fatigue
• Faster-than-normal heartbeat when you stand up
• Vision problems
• Losing weight without trying

Some people who have AAT deficiency may have liver damage. Signs of liver damage include jaundice (a condition that causes your skin and eyes to turn yellow) and swelling in your legs.

Rarely, AAT deficiency can cause skin problems, such as painful lumps or patches.

Your health care provider may test you for AAT deficiency if you have:

• Symptoms of AAT deficiency
• A condition that could be related to AAT deficiency
• Relatives who have AAT deficiency
• Relatives who have a lung or liver disease that could be related to AAT deficiency

AAT deficiency in babies often affects the liver. Your baby may need AAT testing if he or she has signs of liver disease such as jaundice or abnormal liver enzyme tests.

A blood test can check the level of AAT protein in your blood. If the level is lower than normal, it is likely that you have AAT deficiency.

A genetic test is the most certain way to check for AAT deficiency and should be done to confirm the results of the blood test. There are two types of genetic tests:

• A genotype test looks for the more common types of gene changes that can cause AAT deficiency.
• A phenotype test checks for changes in the AAT protein that change how it would normally work.

If your lungs are affected, you may also have lung function tests to see how well your lungs are working.

There is no cure for AAT deficiency, but there are treatments to help with the symptoms and slow the lung damage it causes. Treatment options may include:

• Inhaled medicines to help you breathe better.
• Pulmonary rehabilitation.
• Oxygen therapy.
• Augmentation therapy, which is a lifelong treatment. It raises the levels of the AAT protein in your lungs, using ATT protein taken from the blood of donors. It helps slow down lung damage. It cannot prevent liver damage.
• Lung surgery or a lung transplant, if your lungs are severely damaged.
• Liver transplant, if your liver is severely damaged.

To help prevent or delay lung damage, it is important to quit smoking (if you smoke) and avoid secondhand smoke, dust, and air pollution. Ask your provider If you need to stop drinking alcohol.