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

Authors: Olshen, A. B.; Gold, B.; Lohmueller, K. E.; Struewing, J. P.; Satagopan, J.; Stefanov, S. A.; Eskin, E.; Kirchhoff, T.; Lautenberger, J. A.; Klein, R. J.; Friedman, E.; Norton, L.; Ellis, N. A.; Viale, A.; Lee, C. S.; Borgen, P. I.; Clark, A. G.; Offit, K.; Boyd, J.
Article Title: Analysis of genetic variation in Ashkenazi Jews by high density SNP genotyping
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 FST 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. © 2008 Olshen et al; licensee BioMed Central Ltd.
Keywords: controlled study; single nucleotide polymorphism; genetics; polymorphism, single nucleotide; genetic association; genetic variability; genotype; gene frequency; haplotypes; linkage disequilibrium; haplotype; gene mapping; homozygosity; microarray analysis; homozygote; jews; chromosome 6; chromosome 2; jew; chromosome map; chromosome mapping; principal component analysis; gene linkage disequilibrium; variation (genetics); haplotype map
Journal Title: BMC Genetics
Volume: 9
ISSN: 1471-2156
Publisher: Biomed Central Ltd  
Date Published: 2008-02-05
Start Page: 14
Language: English
DOI: 10.1186/1471-2156-9-14
PUBMED: 18251999
PROVIDER: scopus
PMCID: PMC2259380
Notes: --- - "Cited By (since 1996): 16" - "Export Date: 17 November 2011" - "CODEN: BGMED" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Kenneth Offit
    519 Offit
  2. Larry Norton
    581 Norton
  3. Jaya M Satagopan
    137 Satagopan
  4. Jeffrey Boyd
    111 Boyd
  5. Patrick I Borgen
    238 Borgen
  6. Adam B Olshen
    107 Olshen
  7. Agnes Viale
    205 Viale
  8. Robert J. Klein
    60 Klein
  9. Catherine Lee
    6 Lee