Genetic testing is a rapidly developing field of laboratory testing that has already had a significant impact on the practice of medicine. Individuals may be offered testing or choose to undergo testing for a wide variety of reasons, such as:
Predicting if a disease will develop later in life
Determining if someone is likely to pass a genetic disorder to their children
Determining relationships or ancestry
Before considering or undergoing genetic testing, it is helpful to first understand the basics of how human genetics work. This article may help in understanding this complex field of testing but cannot replace the expertise of a trained genetic counselor. Ask your healthcare practitioner if genetic counseling is right for you.
An individual's total genetic information is called their genome. The genome is made up of chromosomes that are composed of very long double strands of deoxyribonucleic acid, or DNA. Specific DNA segments called genes serve as templates to make (transcribe) ribonucleic acid, or RNA. The information contained in the RNA is translated by tiny molecular machines within our cells into the proteins that govern how the body works.
Each human cell contains 23 pairs of chromosomes (a total of 46 chromosomes). One chromosome from each pair is inherited from an individual's mother and the other is inherited from an individual's father. Twenty-two of the 23 pairs of chromosomes are called autosomes and are numbered 1-22. The remaining two are called sex chromosomes. The sex chromosomes determine a person's physical sex at birth; typically, males have one X and one Y chromosome and females have two X chromosomes. The chromosomes are located in the center of the cell, called the nucleus. There is also a tiny bit of DNA contained within parts of the cell called mitochondria, which are located outside the nucleus in the cytoplasm of every cell.
The long, double stranded DNA (sometimes called "nuclear DNA" because it is located within the cell’s nucleus) that makes up each chromosome contains many genes. There are approximately 20,000 genes in the human genome. The information contained within these genes leads to the production of a huge variety of proteins that serve as the building blocks for our bodies and machines for all of the processes that go on within us.
The genome and genes are made up of multiple chemical “bases” that pair together in a specific pattern. The DNA is structured like a twisted ladder, with two sides and rungs made up of two pieces that fit together. These rungs are created from two of four possible bases: adenine (A), cytosine (C), guanine (G), and thymine (T). Because of their shape, adenine always pairs with thymine and guanine always pairs with cytosine to form a complete rung. These bases are bonded at the sides of the ladder to a sugar and phosphate, which form the vertical backbone of the DNA double helix (the “sides” of the ladder). The base, sugar, and phosphate form a unit called a nucleotide, which is often described by which base (A, C, T, or G) that it contains.
In humans, genes can range in size from a few hundred DNA bases, up to about 2 million bases. It is the difference in the order and number of these bases on each strand of DNA that leads to the uniqueness of each person's genetic makeup. The order of the bases in each gene provides instructions for producing RNA, which in turn provides instructions for producing proteins.
Small differences in the sequence of DNA base pairs can lead to differences in the amount or structure of these proteins, which leads to the uniqueness of each person's physical features and health. Proteins affect many biological processes, so when there are changes in the genetic code (DNA), they can affect how (or whether) a specific protein is produced or works and can lead to a genetic disorder.
Gene expression and gene regulation
This process of going from DNA to protein is called gene expression. Not all genes are expressed at all times or in all locations in the body. The level of gene expression is managed by the complex process of gene regulation. While not yet fully understood, gene regulation lets the body turn genes on and off during development to make different types of cells for different tissues (e.g., muscle cell vs. nerve cell), and allows cells to adapt quickly to changing environmental conditions.
The specific DNA sequences that a person has in their cells is called their genotype.
A person’s observable traits or characteristics, such as hair color or eye color, or even findings of a genetic disease, are called their phenotype.
Differences in our DNA (genotypes) can contribute to differences in our features (phenotypes). Although human genotypes are alike in many ways, small changes in our DNA make us unique beings in both the appearance and function of our bodies. Environmental factors (including nutrition, sun exposure, toxins, poisons, injury and infection) can also affect phenotype.
These differences in our DNA are referred to as “variations” or “variants” and they have different effects on the body. Most genetic variations in DNA do not affect a person’s health. Sometimes, however, differences in our genotypes are related to disease.
Some genetic variants have no effect or only a negligible effect on the body. These variants are not disease-causing. They are called “benign”.
Some genetic variations are common enough (they occur in more than one percent of the population) that they are considered “normal” variations in the DNA. These differences, called polymorphisms, help to identify us as individuals. Some genetic polymorphisms may account for the normal differences we see between people, including characteristics such as eye color, hair color and blood group (A, B, AB or O), and some appear to have no effect at all.
Some variants result in a protein being made differently or not at all. These are usually disease-causing (pathogenic) variants. They are also sometimes called “mutations”. Sometimes the genetic variant gives the protein new activity or a new property that interferes with its normal job. The regulation of the protein may not occur correctly, and it might fail to get turned on or off at the right time or in the right tissue type.
Because there are so many possible changes in the genome, scientists and doctors have not seen them all and do not know what they all may mean for a person’s health. When genetic tests identify these changes, they are called variants of uncertain clinical significance. As science moves forward, more is being understood about human genetics every day. Sometimes, with more research and time, scientists and doctors will be able to determine whether these variants are or are not disease-causing.
(Updated 2015 June 16). Deoxyribonucleic acid (DNA). National Human Genome Research Institute. Available online at https://www.genome.gov/25520880/. Accessed October 2018.
(Reviewed 2017 September 28). Studying genes. National Institutes of Health, National Institute of General Medical Sciences. Available online at https://www.nigms.nih.gov/Education/pages/Factsheet_studyinggenes.aspx. Accessed October 2018.
(Updated 2017 October 3). Genetics. Medline Plus. Available online at https://medlineplus.gov/ency/article/002048.htm. Accessed October 2018.
(2017 October 17). What is a gene? Genetics Home Reference. Available online at https://ghr.nlm.nih.gov/primer/basics/gene. Accessed October 2018.
(2017 October 17). What is a chromosome? Genetics Home Reference. Available online at https://ghr.nlm.nih.gov/primer/basics/chromosome. Accessed October 2018.
Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Nader Rifai. 6th edition, Elsevier Health Sciences; 2017.