Let's face it: the vast majority of genetics studies have been on middle-class, middle-aged white guys. In addition to insulting other ethnic groups by calling the results of these studies the human genome, the lack of diversity poses the risk of serious miscalculations—which is why Archbishop Desmond Tutu has had his complete genome sequenced. In a paper being published in tomorrow’s issue of Nature, scientists report that they have sequenced the complete genomes of four bushmen and one Bantu—Tutu.
The goal was to learn more about human genetic diversity and the effect of genetic variations on health in a way that could shore up the soft underbelly of this field. As I have explained before, whether a gene that has been linked to an elevated risk of some disease indeed raises that risk in a particular individual depends on what other genes that person has—his or her genetic background. That background differs by ethnicity. Since the reference genome was derived from (surprise!) a bunch of white guys, it is crucial to get diverse genomes into the databases.
Only that will tell whether, say, a Basque who carries a "gene for" schizophrenia or colon cancer or diabetes or anything else has the same risk of developing the disease as a Pashtun, Irish-American, or Greek does. As the authors of the Nature paper diplomatically put it, although a number of genes "observed in the Bushmen have been related to [diseases] in other ethnic groups … one should remain skeptical about the validity of untested associations." That is, a disease gene in one genome might be no such thing in another. To take one fascinating example, a mutation in the LIPA gene is thought to cause Wolman disease, a devastating failure in lipid metabolism that is usually fatal by early childhood. But none of the southern Africans with this variation has the disease.
"To know how genes affect health, we need to see the full range of human genetic variation, and southern Africa is the place to look," said biologist Webb Miller of Pennsylvania State University, one of 48 coauthors of the paper.
The four bushmen whose genomes the scientists, led by Stephan Schuster of Penn State, sequenced are all at least 80 years old. Tutu will be 79 in October. Recruiting elderly volunteers gives the scientists almost a full lifetime’s worth of health data that they can mine for links to genetic variations. So far, they have found 1.3 million genetic variants that had not previously been identified. (Just to be clear, this study did have some commercial ties: it received funding from several companies that make DNA-sequencing machines, including Roche Applied Science and Applied Biosystems, and would love to see them become as common as blood-pressure cuffs.)
Including more ethnicities promises to make "the" human genome much more representative of Homo sapiens. To that end, the scientists have made all five genomes freely available to other researchers.
For now, the study has shed light on human evolution. The genetic variations show that southern Africans are genetically distinct from Europeans, Asians, and West Africans—so distinct, says Miller, that "on average, there are more genetic differences between any two bushmen in our study than between a European and an Asian." That reflects the fact that our species was born in East and southern Africa, so peoples there have had a longer time to develop genetic variations. It seems the least geneticists can do would be to make "the" human genome reflect the DNA of the people who have been here the longest, evolutionarily; this is a small step toward righting that wrong.