Haplotype Variation and Linkage Disequilibrium in 313 Human Genes

J. Claiborne Stephens 1*, Julie A. Schneider 1, Debra A. Tanguay 1, Julie Choi 1, Tara Acharya 1, Scott E. Stanley 1, Ruhong Jiang 1, Chad J. Messer 1, Anne Chew 1, Jin-Hua Han 1, Jicheng Duan 1, Janet L. Carr 1, Min Seob Lee 1, Beena Koshy 1, A. Madan Kumar 1, Ge Zhang 1, William R. Newell 1, Andreas Windemuth 1, Chuanbo Xu 1, Theodore S. Kalbfleisch 1, Sandra L. Shaner 1, Kevin Arnold 1, Vincent Schulz 1, Connie M. Drysdale 1, Krishnan Nandabalan 1, Richard S. Judson 1, Gualberto Ruaño 1, and Gerald F. Vovis 1


1 Genaissance Pharmaceuticals, Inc., Five Science Park, New Haven, CT 06511; USA.

* To whom correspondence should be addressed. E-mail: c.stephens@genaissance.com.


Submitted on January 30, 2001
Accepted on June 7, 2001
Published Online July 12, 2001;


Variation within genes has important implications for all biological traits. We identified 3,899 Single Nucleotide Polymorphisms (SNPs) that were present within 313 genes from 82 unrelated individuals of diverse ancestry, and we organized the SNPs into 4,304 different haplotypes. Each gene had several variable SNPs and haplotypes that were present in all populations, as well as a number that were population-specific. Pairs of SNPs exhibited variability in the degree of linkage disequilibrium that was a function of their location within a gene, distance from each other, population distribution, and population frequency. Haplotypes generally had more information content (heterozygosity) than did individual SNPs. Our analysis of the pattern of variation strongly supports the recent expansion of the human population.