Snips of DNA of only 270 people from just four world locations provide a reliable map of genetic disease variations in the human genome for nearly all populations around the world.
U-M scientists evaluated the worldwide coverage of a database of genetic markers and variations spread across the genome, called the HapMap, which was released one year ago by an international research consortium.
That team had identified about 4.5 million single-letter differences in DNA, called single nucleotide polymorphisms or SNPs (say Snips) from the genomes of the Yoruba people in Nigeria, Chinese from Beijing, Japanese from Tokyo, and a group of European Americans. Each population's particular collection of SNPs is called a haplotype, which is what the name HapMap refers to.
The HapMap database of genetic markers allows researchers to select markers that will be useful to their studies and also to develop a standard set of markers to be used in studies of many diseases. However, until now, the extent to which the genetic variants in the HapMap database represented the rest of the world's populations had not been studied.
"The variants in the HapMap provide a good set of markers to use to test for diseases such as diabetes in most human populations," said study author Noah Rosenberg, assistant professor in the Life Sciences Institute, the Bioinformatics Program and the department of Human Genetics at the U-M Medical School.
Rosenberg's U-M group studies genetic variation across populations and wanted to find the extent to which the genetic variants in the HapMap would apply to populations that were not part of that project. His team collected data from 927 individuals in 52 different world populations and measured the proportion of variants in these populations that were already contained in the HapMap.
"Initially we expected that there would be many parts of the world where the coverage by the HapMap was inadequate," Rosenberg said. "Instead, what we found was that the variation in the HapMap does a reasonable job of capturing the genetic variation in nearly all populations."
Therefore, researchers like Rosenberg who study disease variants in populations will be able to use the HapMap to test genetic markers spread out across the genome to investigate any differences related to that disease. Rosenberg has previously shown that the geographic distribution of haplotypes strongly reflects human history, with a loss of diversity as distance increases from the human species' ancestral range in Africa. In fact, this history explains part of the current finding.
"Except in some parts of Africa, where haplotypes are older and more distinctive, human populations have diverged recently enough that their haplotypes are fairly similar," Rosenberg said.
"These variations are of interest not only for the study of human history but also for disease-related studies," said Rosenberg. "That we can use the history of human evolution in the search for disease genes turns out to be a very powerful idea."
The paper "A worldwide survey of haplotype variation and linkage disequilibrium in the human genome" was published in the advance online version on the Nature Genetics website on October 22, 2006.