I do not know how many hours of “Twilight Zone” I’ve watched in the past 24 hours, but burrowing in for the TZ marathon is how I enjoy greeting the new year. Iconic host Rod Serling is the perfect date. If I were to project in the medical-science zone, as Serling does in his science-fiction zone, I would see a signpost up ahead on which is written one word: genome.
Basic scientists and physicians alike are excited about how knowledge of the human genome can translate into better disease diagnosis, treatment, and prevention for individual patients.
Last year, I tried to learn from the experts about genomics and what it portends for the future, and I’ve shared with you some of my lessons. On the first day of the new year, I return to square one and provide a primer for understanding genomics. To stay abreast of medical breakthroughs—and to distinguish true wheat from over-hyped chaff–you need to know the basics. Consider the following a crib sheet:
What is a genome?
A genome is all of a person’s or another living organism’s DNA. Genomics is the study of genomes.
What is DNA?
DNA is a molecule of deoxyribonucleic acid. The DNA molecule carries the hereditary material in humans and almost all other living organisms. DNA transports genetic information from one cell to the next (through cell division) and from one generation of an organism to the next. Most organisms use DNA for coding life’s blueprint, whether it’s yeast, a fruit fly, a mouse, or a human being.
How is the genetic information in DNA stored?
Information in DNA is stored as a CODE made up of four chemical bases: adenine (A), thymine (T), cytosine (C), and guanine (G). DNA bases pair up with each other—A with T, and C with G—to form base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and phosphate form a nucleotide, and these nucleotides form a spiral called a double helix. This is the DNA ladder that you’re accustomed to seeing. The base pairs are its rungs and the sugar and phosphate molecules form its vertical sides.
Each chemical base is a building block of a protein. 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. You may think of the order of the letters as forming words and sentences, hence, a language.
Scientists achieved SEQUENCING of these building blocks—i.e., they determined the order of A, T, C, and G in the genome—in 2003, hence the explosion in genomic research in the past 10-plus years. (See chromosomes and genes, below.)
Where is DNA found in human cells?
The chemical blueprint for human life resides within DNA that is packaged into chromosomes found within the nucleus of EACH of our trillions of cells. DNA in cell nuclei is called nuclear DNA. Some DNA is also found in cell mitochondria, which are structures that convert energy from food into a form that the cell can use. Hundreds to thousands of mitochondria are located in the fluid (cytoplasm) that surrounds every cell nucleus. DNA within them is known as mitochondrial DNA or mtDNA.
What are chromosomes?
Chromosomes are thread-like structures made up of DNA that is tightly coiled many times around proteins. Chromosomes are not visible under a microscope except when cells are dividing. 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. Hence, we have 46 chromosomes in each cell. Each set of 23 chromosomes, which is essentially one copy of the human genome, contains 3 billion letters or ordered repetitions of A, T, C, and G. More than 99 percent of these 3 billion letters are the same in all people. This similarity enabled sequencing.
“Words” consisting of three of the four lettered chemicals form 20,000+ sentences, each of which is a gene.
What is a gene?
A gene is a functional unit (i.e., sentence) of information in the genome, varying in size from a few hundred DNA bases to 2 million bases. Each gene provides instructions for a protein molecule. Although sequencing of the human genome was achieved nearly 14 years ago, there is still much about genes that scientists do not know.
Human beings have about 22,000 genes, roughly the same number as mice have, according to Dr. Lawrence C. Brody of the National Human Genome Research Institute (NHGRI) at the National Institutes of Health in Bethesda, Md. Genes are “punctuated along the genome,” Brody explained in a lecture I attended at the Smithsonian last year, and interact with each other.
We have two copies of each gene because we inherit a set of 22,000 genes from each of our parents. Most genes are the same in all people, but a small number—less than 1 percent of the total—are slightly different among people. Faulty genes can cause cancer and other diseases. Thus far, according to Brody, 5,000 diseases caused by changes (mutations) in DNA have been identified.
How much of the human genome consists of genes?
Genes take up 1 to 2 percent of the genome.
I repeat: GENES TAKE UP AT MOST ONLY 2 PERCENT OF THE HUMAN GENOME.
DNA ≠ just genes
Genome ≠ only genes
Genomics ≠ 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.”
For an elaboration on this DNA primer, see the National Library of Medicine (NLM) at https://ghr.nlm.nih.gov/primer/basics/dna.
I find it amazing and fascinating that 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.
Medicine is steadfastly moving toward an approach to disease treatment and prevention that, according to the NIH, “seeks to maximize effectiveness by taking into account individual variability in genes, environment, and lifestyle.”
As we start off 2017, after a year that could be described as very turbulent—certainly U.S. politics and international conflicts were—I think it’s wise to keep in mind our similarities. On a molecular basis, we have an awful lot in common. Appearances are deceiving.
I wish you all a healthy, productive, and enlightening new year.