Research article

Analysis of genetic variation in Ashkenazi Jews by high density SNP genotyping

Adam B Olshen¹ , Bert Gold⁶ , Kirk E Lohmueller⁸ , Jeffery P Struewing⁷ , Jaya Satagopan¹ , Stefan A Stefanov⁶ , Eleazar Eskin⁹ , Tomas Kirchhoff³ , James A Lautenberger⁶ , Robert J Klein⁴ , Eitan Friedman¹⁰ , Larry Norton³ , Nathan A Ellis¹¹ , Agnes Viale⁵ , Catherine S Lee² , Patrick I Borgen² , Andrew G Clark⁸ , Kenneth Offit³ and Jeff Boyd^2,3

¹Departments of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

²Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

³Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

⁴Programs in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

⁵Molecular Biology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

⁶Laboratories of Genomic Diversity, National Cancer Institute, Bethesda, MD, USA

⁷Population Genetics, National Cancer Institute, Bethesda, MD, USA

⁸Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA

⁹Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, USA

¹⁰Chaim Sheba Medical Center, Tel-Hashomer, and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

¹¹Department of Medicine, University of Chicago, Chicago, IL, USA

author email corresponding author email

BMC Genetics 2008, 9:14doi:10.1186/1471-2156-9-14

Published:	5 February 2008

Abstract

Background

Genetic isolates such as the Ashkenazi Jews (AJ) potentially offer advantages in mapping novel loci in whole genome disease association studies. To analyze patterns of genetic variation in AJ, genotypes of 101 healthy individuals were determined using the Affymetrix EAv3 500 K SNP array and compared to 60 CEPH-derived HapMap (CEU) individuals. 435,632 SNPs overlapped and met annotation criteria in the two groups.

Results

A small but significant global difference in allele frequencies between AJ and CEU was demonstrated by a mean F_ST of 0.009 (P < 0.001); large regions that differed were found on chromosomes 2 and 6. Haplotype blocks inferred from pairwise linkage disequilibrium (LD) statistics (Haploview) as well as by expectation-maximization haplotype phase inference (HAP) showed a greater number of haplotype blocks in AJ compared to CEU by Haploview (50,397 vs. 44,169) or by HAP (59,269 vs. 54,457). Average haplotype blocks were smaller in AJ compared to CEU (e.g., 36.8 kb vs. 40.5 kb HAP). Analysis of global patterns of local LD decay for closely-spaced SNPs in CEU demonstrated more LD, while for SNPs further apart, LD was slightly greater in the AJ. A likelihood ratio approach showed that runs of homozygous SNPs were approximately 20% longer in AJ. A principal components analysis was sufficient to completely resolve the CEU from the AJ.

Conclusion

LD in the AJ versus was lower than expected by some measures and higher by others. Any putative advantage in whole genome association mapping using the AJ population will be highly dependent on regional LD structure.