摘要
Genetic variations and their functional implications have been one of the focuses in recent genome research. With the release of the HapMap by the International Consortium, and the availability of the ultra-high-volume genotyping platform, it will soon be possible to use genome-wide association ap- proach to identify genetic variations responsible for complex traits/diseases. While the power of this ap- proach is generally agreed, it is a debated issue as to how much population difference should be exploited, and how best it should be applied. To address this issue we have sequenced 7 genes in the centromeric region of chromosome 15, investigated their SNPs, SNP frequencies, tagSNPs, LD structures, and hap- lotypes in 50 Tibetan subjects, and compared them with those from the Han population. Genetic diversi- ties between the two populations were also quantified. Our results show that the overall genetic variation between the two populations is very little, but there are differences, primarily in allele frequencies, which is a dominating factor for haplotypes and tagSNPs. In general Tibetans have longer LD and less diversity inthe region studied. These data provide genetic evi- dence for the close relationship between the two populations, and support the idea that all populations are fundamentally the same, but also indicate popu- lation variations, particularly in allele frequency, should be taken into account in complex traits/ dis- eases analysis. Data obtained in this investigation not only help us understand the genome region, but also provide road maps for variation study in the genes/ region in Tibetan population.
Genetic variations and their functional implications have been one of the focuses in recent genome research. With the release of the HapMap by the International Consortium, and the availability of the ultra-high-volume genotyping platform, it will soon be possible to use genome-wide association approach to identify genetic variations responsible for complex traits/diseases. While the power of this approach is generally agreed, it is a debated issue as to how much population difference should be exploited, and how best it should be applied. To address this issue we have sequenced 7 genes in the centromeric region of chromosome 15, investigated their SNPs, SNP frequencies, tagSNPs, LD structures, and haplotypes in 50 Tibetan subjects, and compared them with those from the Han population. Genetic diversities between the two populations were also quantified Our results show that the overall genetic variation between the two populations is very little, but there are differences, primarily in allele frequencies, which is a dominating factor for haplotypes and tagSNPs. In general Tibetans have longer LD and less diversity in the region studied. These data provide genetic evidence for the close relationship between the two populations, and support the idea that all populations are fundamentally the same, but also indicate population variations, particularly in allele frequency, should be taken into account in complex traits/diseases analysis. Data obtained in this investigation not only help us understand the genome region, but also provide road maps for variation study in the genes/ region in Tibetan population.
基金
supported by the 863 Project(Grant No.2001AA221102)
the Natural Science Foundation of Guangdong Province(Grant No.031673)
the Guangzhou Municipal Science and Technology Foundation(Grant Nos.2002Z3-C7191&2004Z3-C7501)
the China Medical Board of New York(Grant No.01-759).
