Reich Lab
Human History, Evolution and Disease Gene Mapping
This lab does both theoretical and experimental work
in human population genetics. We develop
mathematical ideas and apply them to data we
collect in the laboratory.
Disease gene mapping in recently mixed populations
Traditionally, medical geneticists have studied families with strong disease inheritance patterns to find genes. But genes causing common diseases have only weak inheritance in families. To find genes causing common disease, we have been working on association mapping techniques that study large numbers of unrelated people and have greater statistical power to detect subtle effects. We have focused on populations of recently mixed ancestry like African Americans and Latinos, developing statistical techniques (1) and genetic resources (2, 3) to make gene mapping studies powerful in these groups. So far we have applied these techniques to find gene loci for multiple sclerosis (4) and prostate cancer (5, 6).
Population diversity as a confounder in disease gene mapping studies
Self-defined groups like “European Americans” are comprised of many ancestries. This leads to “population stratification”: statistical differences between cases and controls that are due to differences in their ancestry rather than any real gene effect. We have worked on characterizing the problem (7) and on developing practical methods to understand (8) and correct for it (9, 10).
History, natural selection, and evolution as learned from genetic data
We analyze how the patterns of variability in the genome are shaped by the forces of mutation (11), recombination (12, 13), natural selection and population history. We helped develop some of the first tests of recent natural selection in the genome, finding powerful signals at two genes affecting malaria resistance (14).
Genetic analysis of speciation
We also have been studying patterns of genetic variability on a longer time scale. We compared chromosome X and the rest of the genome in humans, chimpanzees, gorillas, orangutans and macaques to show that the history of human-chimpanzee splitting was complex, possibly involving hybridization after initial separation (15).