The average person walks around with defective copies of 250 to 300 genes, a new close-up snapshot of human genetic diversity reveals, on top of about 75 DNA variants associated with disease.
An analysis of data gathered during the pilot phase of the 1000 Genomes Project appears in the Oct. 28 Nature, with a companion paper published in the Oct. 29 Science.
Despite its name, the project is an effort to catalog genetic variation in about 2,500 people, with special emphasis on finding more of the relatively rare variants present in less than 5 percent of the population. The information can be used to search for links between DNA variation and disease, and to study events in human prehistory that have left a genetic footprint.
“The veil has been lifted for us on a whole new level of genetic diversity,” says Evan Eichler, a geneticist at the University of Washington in Seattle who led a team investigating genes with variable numbers of copies.
The project identified about 15 million different one-letter DNA spelling variations, 1 million small insertions or deletions of portions of chromosomes, and about 20,000 larger missing or duplicated chunks of DNA in the human genetic instruction book. Among these are about 8 million newly identified genetic variants. Each person carries about 3 million spelling variations known as single nucleotide polymorphisms, or SNPs.
In addition, researchers report in the Science paper that they have discovered about 1,000 genes that are duplicated in most people, including 44 gene families whose extra copies were previously unknown. About half of duplicated genes appear in varying numbers in the 159 people studied. Most genes occur in two copies — one inherited from mom and the other from dad — but sometimes genes are copied over and over again. Most of the duplicated genes the researchers found varied between zero and five copies per person, but a few extreme examples had ranges between five and 368 per person.
About five years ago roughly half of the variants discovered each time that researchers deciphered another person’s genetic blueprint were new, says David Altshuler, a geneticist at the Broad Institute in Cambridge, Mass., and one of the leaders of the 1000 Genomes Project. “Now, about 95 percent of what you’ll find in the next person’s genome is already in the database,” he says.
Parts of the genome where duplicated genes occur both expand and contract rapidly, like accordions, Eichler says, even from one generation to the next.
Eichler’s group has found tantalizing evidence that duplicated genes may be at the root of brain changes between humans and great apes. Comparison of DNA from a chimpanzee, a gorilla and an orangutan with that of 159 humans from the 1000 Genomes Project shows that humans tend to have more copies of genes involved in brain function and growth.
In this early stage of the project, researchers closely read the entire genome of six people from two families, with each family composed of a mother, father and daughter. One of the families belongs to the Yoruba tribe in Ibadan, Nigeria; the other is a family of European descent living in Utah. In addition, researchers skimmed the genetic instruction books of 159 people from Nigeria, Utah, Japan and China. Researchers also read the genetic equivalent of CliffsNotes of 697 other people by examining just the protein-producing parts of 906 genes.