5.2: Genome

Background Information (Read BEFORE Lab)

What is a genome?

A genome is the complete set of genes or genetic material present in a cell or organism.

Your genome is the operating manual containing all the instructions that helped you develop from a single cell into the person you are today. It guides your growth, helps your organs to do their jobs, and repairs itself when it becomes damaged. Your genome is unique to you. The more you know about your genome and how it works, the more you'll understand your own health and make informed health decisions.

Does my genome determine everything about me?

Not entirely. Genomes are complicated, and while a small number of your traits are mainly controlled by one gene, most traits are influenced by multiple genes. On top of that, lifestyle and environmental factors play a critical role in your development and health. The day-to-day and long-term choices you make, such as what you eat, if you smoke, how active you are, and if you get enough sleep, all affect your health. The way you live influences how your genome works.

Genetic Diseases

Changes in the DNA sequence are called genetic variants. The majority of the time, genetic variants have no effect at all. However, sometimes, the effect is harmful: just one deletion or alteration of just one nucleotide may result in a damaged protein, extra protein, or no protein at all, with serious consequences for our health. Additionally, the passing of genetic variants from one generation to the next helps to explain why many diseases run in families, such as in sickle cell disease, cystic fibrosis, and Tay-Sachs disease.

Genetic Testing

Predictive testing is for those who have a family member with a genetic disorder. The results help to determine a person’s risk of developing the specific disorder being tested for. These tests are done before any symptoms present themselves.

Diagnostic testing is used to confirm or rule out a suspected genetic disorder. The results of a diagnostic test may help you make choices about how to treat or manage your health.

Pharmacogenomic testing tells you about how you will react to certain medications. It can help inform your healthcare provider about how to best treat your condition and avoid side effects.

Reproductive testing is related to starting or growing your family. It includes tests for the biological father and mother to see what genetic variants they carry. The tests can help parents and healthcare providers make decisions before, during, and after pregnancy.

Direct-to-consumer testing can be completed at home without a healthcare provider by collecting a DNA sample (e.g., spitting saliva into a tube) and sending it to a company. The company can analyze your DNA and give information about your ancestry, kinship, lifestyle factors and potential disease risk.

Forensic testing is carried out for legal purposes and can be used to identify biological family members, suspects, and victims of crimes and disasters.

Genomic impact on everyday life

Ethical and Social Questions: The scientists who launched the Human Genome Project recognized immediately that having a complete human genome sequence would raise many ethical and social issues. In 1990, the Ethical, Legal, and Social Implications (ELSI) Research Program was formally established at the National Institutes of Health (NIH) as an integral part of the Human Genome Project. The research supported by this program ranges from genomics and health disparities to inclusion of diverse populations in genomics research, to whether people should have the right to refuse to know genomic testing results.

Consent and Privacy: Among the major areas of study in ELSI research are questions about consent and privacy. As new areas of genomics have developed in recent years (like learning about microbiomes), researchers have needed to continually update their guidelines, so as to help people understand the relevant risks and benefits before signing up to be a research participant. Such studies are overseen by Institutional Review Boards (or IRBs), and these boards are made up of scientists, ethicists, and members of the community. An IRB must approve any research projects involving humans.

The widespread availability of genomic data has brought changes to privacy considerations as well. When a test is performed on your DNA how the privacy of your genomic data is handled is a concern for many. Since you share half of your genome with each of your parents, and half with each of your children, the information is not just about your genome.

Answer the following questions before moving on.

Let's say that one of your parents learns from a genetic test that they have Huntington's disease, which is often diagnosed quite late in life. This gives you a 50% chance of carrying the same genetic mutation for this fatal neurological disease. Some people react to such information by wanting to know right away what their future might be, while others do not want to know.

STOP AND THINK.

Take a moment to answer the following question.

Should you be able to stop your relatives from revealing genomic information that could be relevant to you as well?

Discrimination: Concerns also exist about potential discrimination based on information about a person's DNA. In 2008, President Bush signed into law the Genetic Information Nondiscrimination Act (or GINA for short). This law is now enforced by multiple federal agencies, including the United States Equal Employment Opportunity Commission. GINA also prohibits health insurers from discriminating against anyone based on their genetic information when determining coverage or rates.

Direct-to-Consumer testing: Advances in genomics since the Human Genome Project have led to an explosion in at-home, or "direct to consumer" genomic testing.

There are now numerous companies offering you a service to learn more about yourself or your family through DNA testing. The global "direct-to-consumer" (or DTC) genomic testing market was valued at $117 million in 2017, suggesting millions of people are purchasing these tests.

One popular application of such DTC genomic testing is for revealing family ancestry or genealogy. For example, the company Ancestry.com started as a place to search historical and family records to gain genealogical clues, and has now expanded to offer genomic tests for people who seek information about their genomic ancestry.

Another prominent company, 23andMe, was established in 2006 with the goal of offering genomic testing directly to people interested in getting DNA-based health, traits, and ancestry information. Some of the information reported back to customers are surprising facts, such as whether you have dry or wet earwax due to genomic variants or if you are likely to prefer salty/savory snacks compared to sweets. They also offer their customers the opportunity to provide their genomic information to large research studies, such as recruiting 25,000 people for a study on the genomics of schizophrenia and bipolar disorder. These research studies can provide another avenue to advance genomic science and improve human health on a rapid basis.

In recent years, there have been a number of stories involving people who found new family members or famous relatives through DTC genomic testing. Some people have found out that family members who they previously thought were genetic relatives were actually not biologically related to them, or even that their own identity is not what they thought.

Let's take one example. Some DTC genomic testing companies claim to provide information about a child's ability in certain sports. You want to find out if your daughter will be a sprinting champion. There is validated science behind the claim that certain variants in the gene ACTN3 control different types of muscle fibers (called "fast-twitch" or "slow-twitch"), and many successful sprinters have the "fast-twitch" genomic variants. But the prediction power stops there. ACTN3 variants are just one factor among many, many others - genomic, environmental, and social. So, even if your daughter does not have the "fast-twitch" genomic variant, that does not mean she cannot become an accomplished sprinter. Looking for genomic variants in children, such as the one for "fast-twitch" muscle fibers, also raises ethical questions.

STOP AND THINK

Answer the following question.

1. Since children may not be able to consent to such a test and/or they might be unable to fully understand what such testing might mean for them today or in their future, is it okay for parents to have their children tested? Might you treat your child differently based on the results?

Pharmacogenomics: Pharmacogenomics is a branch of pharmacology concerned with using DNA and amino acid sequence data to inform drug development and testing. An important application of pharmacogenomics is correlating individual genetic variation with drug responses.

Agricultural: Genomics enables farmers to accelerate and improve plant and animal breeding practices that have been in use for thousands of years.The ability to read genome sequences coupled with technologies that introduce new genes or gene changes allows us to speed up the process of selecting desirable traits in plants and animals.

Genome modification: The ability to read genome sequences coupled with technologies that introduce new genes or gene changes now allow people to speed up the ability to select for desirable traits in plants and animals. By mimicking natural processes, scientists can selectively add traits like resistance to herbicides in plants. The resulting offspring have been called genetically modified organisms (or GMOs). One example is "Golden Rice," which is a rice strain that has small bits of corn and bacterial DNA added to its genome. These extra genes allow the rice to produce beta carotene (a vitamin A precursor). The lack of vitamin A affects millions in Africa and Asia, causing blindness and immune system deficiencies.

Food Safety Monitoring: One of the most important agricultural advances in the 20th century has been the ability to move food around the globe to people who need it. Unfortunately, food supplies sometimes have unwanted guests along for the ride, such as bacterial pathogens. When people eat contaminated food, they can get very sick or even die, so it's important to find the pathogens and eliminate them. The U.S. Food and Drug Administration (FDA) has an entire

network set up for whole genome sequencing of bacterial contaminants in food, called GenomeTrakr. In 2017, this database had over 5800 bacterial sequences added on average each month, as scientists tracked new outbreaks in the quest to keep our food safe. FDA scientists work closely with others from the U.S. Centers for Disease Control and Prevention, the U.S. Department of Agriculture's Food Safety and Inspection Service, and state health departments to identify bacteria that might cause outbreaks from food contamination. Rounding out this network, the National Center for Biotechnology Information keeps track of what foods are linked to each incident, as well as in human patients who got sick. These information sources have been crucial for lowering the impact of foodborne illnesses over time.

Human Origins and Ancestry: Advances since the Human Genome Project allow us to compare genome sequences among humans, living and long-deceased, and to trace our collective ancestral history.

Species History: Nearly 20 years ago, scientists developed techniques for extracting small amounts of DNA from ancient samples, like bones or fur or even soil, and used very sensitive methods for sequencing the extracted DNA. Genomic studies like these have allowed us to examine human genomes from around 500,000 years ago when our ancestors (the species Homo sapiens) were diverging from other similar species, such as Homo neanderthalensis or Neanderthals.