To begin to understand the study of genomics and its potential for deciphering the molecular bases of human disease and, perhaps eventually, for improving human health, one needs a genomics primer, what Dr. Lawrence C. Brody of the National Human Genome Research Institute (NHGRI) at the National Institutes of Health in Bethesda, Md., calls “Genomics 101.”
Brody, who has a Ph.D. in human genetics from Johns Hopkins University, gave such an overview at the first class of the Smithsonian Associates-NIH-sponsored lecture series, “The Pulse on Modern Medicine,” in Washington, D.C., Sept. 6. What he introduced was literally a new language code consisting of 6 billion “letters” that form 20,000 sentences made up of words that are only three letters long.
Welcome to genomics-speak, which is all about coding. If you understand computer coding, you should be a whiz at genomics. Me, I prefer clinical medicine to molecular science, but I’ll give Genomics 101 a try.
GENOME = ALL OF YOUR DNA
According to Brody, “Genome is a fancy word for all of your DNA,” and genomics, a discipline that is only three decades old, is the study of genomes.
DNA, which is short for deoxyribonucleic acid, serves as the model of heredity, carrying genetic information from one cell to the next (through cell division) and from one generation of an organism to the next. You may think of DNA as raw material.
Appropriately enough, Brody has fancy titles to describe what he does at the NHGRI, two of which are director of the Division of Genomics and Society in the Extramural Research Program and senior investigator in the Medical Genomics and Metabolic Genetics Branch in the Division of Intramural Research. The NHGRI, according to its director, Eric D. Green, M.D., Ph.D., is the largest organization in the world dedicated solely to genomics research.
Genomics is not synonymous with genetics. “Genomics,” Brody explained, “refers to the study of the entire genome of an organism whereas genetics refers to the study of a particular gene.” He further defined genetics as “the study of inherited characteristics.” (More about genes below.)
DNA PACKAGED IN CHROMOSOMES
Most organisms use DNA for coding life’s blueprint, whether it’s yeast, a fruit fly, a mouse, or a human being. In humans, that blueprint resides within the double-stranded fibers of DNA that are packaged into chromosomes within the nucleus of each of our trillions of cells. (Mitochondria also have a small amount of their own DNA.)
DNA is made of four different building blocks of a protein, each containing one of the following chemicals: adenine (A), thymine (T), cytosine (C), and guanine (G). The order of these building blocks, which are known by the letters A, T, C, and G, in the human genome encodes the biological instructions that tell each of our cells what to do and when to do it. (See the coding above in the illustration. Now imagine 6 billion of these letters in a single genome. Those who speak genomics will recognize TGA as a stop between sentences.)
As you no doubt are aware, the typical human cell contains 23 pairs of chromosomes, with one set of 23 coming from each of our parents. Each set of 23 chromosomes, which is essentially one copy of the human genome, contains 3 billion letters (ordered repetitions of A, T, C, and G), hence the 6 billion total.
“Words,” consisting of three of the four lettered chemicals, form 20,000 sentences, each of which is a GENE. Brody described a gene as a functional unit (i.e., sentence) of information in the genome. Each gene provides instructions for the synthesis of a protein molecule.
For an elaboration on my DNA primer, see the National Library of Medicine (NLM) at https://ghr.nlm.nih.gov/primer/basics/dna.
Here’s now the NLM defines a gene: https://ghr.nlm.nih.gov/primer/basics/gene.
And how it explains proteins, which are essential to life: https://ghr.nlm.nih.gov/primer/howgeneswork/protein.
Human beings have 22,000 genes, roughly the same number as mice have. These genes are “punctuated along the genome,” Brody said, and interact with each other. Humans have two copies of each gene because we inherit a set of genes from each of our parents. Needless to say, scientists don’t know what most of our genes actually do. They do know, however, that genes take up 2 percent of the genome.
Faulty genes can cause cancer and other diseases. Thus far, according to Brody, 5,000 diseases caused by “changes” in DNA have been identified. There are many different ways in which DNA can change, and a mutation can occur, but Brody did not elaborate upon them. (Beyond the scope of a primer.) He said only that most diseases are not caused by a “single genomic variance, but by multiple variances,” including those induced by the environment.
Amazingly, 99.9 percent of one person’s genome is identical to any other person’s. In fact, a human being’s genome is 85 percent identical to that of a mouse! According to literature from the National Genome Research Institute, when the order of letters, or “sequences” of adenine, thymine, guanine, and cytosine, of any two people’s genomes are compared, they reveal a different letter roughly once every thousand positions.
You may enjoy viewing an animated video online that explains Genomics 101 better than I just did. If so, click on the following link on the website, “Genome: Unlocking Life’s Code”: https://unlockinglifescode.org/learn/the-animated-genome. “Genome: Unlocking Life’s Code” is a five-year traveling exhibit sponsored by the Smithsonian Institution and the NIH that opened at the National Museum of Natural History. It is currently on its way to Kansas.
In my next blog, I’ll tackle precision medicine, which is an initiative in healthcare to factor into treatment decisions the differences between individual patients, in terms of genomics, physiology, lifestyle, and environmental exposure. It is not the same as genomic medicine, the most-publicized example of which is the DNA sequencing of tumors that is currently being done to determine the best therapy for a given cancer.
I already have read articles by credible scientists who say that precision medicine is largely hype–like the similarly named and hyped “personalized medicine” before it–and cannot work. President Obama himself raised the political stakes when he announced a Precision Medicine Initiative in his 2015 State of the Union address. I’ll weigh in as soon as I’ve done my homework.