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Human Molecular Genetics, 2002, Vol. 11, No. 12 1381-1390
© 2002 Oxford University Press

Population differences in haplotype structure within a human olfactory receptor gene cluster

Idan Menashe, Orna Man, Doron Lancet* and Yoav Gilad

Department of Molecular Genetics and the Crown Human Genome Center, The Weizmann Institute of Science, Rehovot 76100, Israel

Received January 11, 2002; Accepted April 9, 2002

We investigated the population differences in patterns of single nucleotide polymorphisms (SNPs) for a 400 kb olfactory receptor (OR) gene cluster on human chromosome 17p13.3. Samples were drawn from 35 individuals, of four different ethnogeographical origins: Pygmies, Bedouins, Yemenite Jews and Ashkenazi Jews. Of the 74 SNPs identified, two segregated between pseudogenized and intact ORs, while a third involved a change in a highly conserved motif proposed to mediate ligand-induced signal transduction. Linkage disequilibrium (LD) was computed based on phase inference across the cluster using Clark's haplotype subtraction algorithm. We also calculated LD directly from the genotypes using the expectation-maximization (EM) algorithm. Both methods yielded very similar results. Our analyses revealed substantial differences in nucleotide diversity, haplotype distribution and LD patterns among the different human populations. In particular, the two Jewish populations had low haplotype diversity and negligible decay of LD across the entire genomic region. Intriguingly, the three functional SNPs segregated at different frequencies in the different ethnogeographical groups, with the Pygmies having higher frequencies of the intact OR genes. Our data suggests that OR genes may have evolved to create different functional repertoires in distinct human populations.

* To whom correspondence should be addressed. Tel: +972 8 9343683 or 9344121; Fax: +972 8 9344487; Email: doron.lancet{at}weizmann.ac.il


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