Family Matters

TIME Explains: Genome Sequencing

Time’s Bonnie Rochman explains how doctors are mapping out all the genes in a person’s body

  • Share
  • Read Later
Spencer Lowell for TIME

Nearly every cell in the human body—from the ones in the fingernails to the ones deep inside the brain—contains a complete set of DNA, the operating instructions that influence everything from a person’s hair color to susceptibility to disease.

For years, doctors have been able to test specific genes to detect the presence of mutations associated with disorders such as cystic fibrosis and sickle cell disease. But only recently have scientists been able to map out a person’s entire genetic code, or genome, by sequencing all 20,000 or so genes in one fell swoop. (Read TIME’s five-part series on the promise — and pitfalls — of sequencing children’s genomes)

“Sequencing a gene is like reading a book one letter at a time to look for any spelling mistakes,” says Dr. David Miller, assistant director in the genetics diagnostic lab at Children’s Hospital Boston. To carry out this book analogy, whole genome sequencing (WGS) is the equivalent of running spellcheck on every volume in a library. “We all have the same 20,000 genes, but we all have some spelling mistakes compared to one another,” says Miller.

DNA resembles a long, twisty ladder formed by two strands of genetic material that connect to create what’s called a “double helix.” Each rung of the ladder joins together a pair of molecules called nucleotides: adenine (A), thymine (T), cytosine (C) and guanine (G). A always teams up with T, and C always pairs with G. Slight variations in the order of these pairs are what make a person unique. (The vast majority of your genome is identical to the guy sitting next to you at Starbucks.) Some variations cause disease, and some don’t.

Genes, which are made up of DNA, are linked together in large chains called chromosomes. Most people have 23 pairs of chromosomes—half of each pair is inherited from mom and the other half from dad. The 23rd pair of chromosomes determines a person’s sex: inherit an X chromosome from both parents, and you’ll be a girl. But if mom passes down an X chromosome and dad a Y chromosome, you’ll be a boy.

Chromosomes house different genes. Researchers know, for instance, that chromosome 1 contains the gene that controls whether you’re susceptible to some forms of malaria while chromosome 16 has a gene that influences hair color.

Some people have a missing chromosome or an extra one,  which can cause medical problems; others have an inverted chromosome that doesn’t appear to affect their health. Genetic mutations can be inherited or can spring up randomly on their own.

To sequence a person’s genome, doctors need to collect less than a teaspoon of blood or saliva. Then chemicals are used on this sample to break open the cell membranes and gather the DNA that had been housed inside them. Enzymes strip away surrounding proteins to isolate a clump of tiny, whitish strands of DNA that, according to Dr. Mike Bamshad, chief of genetic medicine at Seattle Children’s Hospital, “looks like a little piece of snot.” That genetic material is placed in sophisticated machines that “read” each of the 3 billion base pairs that make up a person’s genetic code.

It generally takes a couple months to sequence a person’s genome. Much of that time is spent reconfirming results for individual “spelling mistakes,” which need to be compared to a composite genome made of many people’s DNA.

Within the next few years, experts expect the turnaround time to improve and the cost to drop so much that analyzing a person’s genome will be no more expensive than zeroing in on just one gene.