Analysis of genetic variation in Ashkenazi Jews by high density SNP genotyping. BMC Genet 9:14

Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
BMC Genetics (Impact Factor: 2.4). 02/2008; 9(1):14. DOI: 10.1186/1471-2156-9-14
Source: PubMed


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.
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.
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.

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Available from: Bert Gold, Oct 06, 2015
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    • "Mean pairwise F st values showed that experimental groups differed (Table 1). However, because F st values as high as 0.05 generally indicate negligible genetic differences (Olshen et al. 2008), and given that the average population pairwise F st value for this subspecies in a previous study was 0.20 (Brown et al. 2011), we concluded that the differences observed in this study were not biologically meaningful and these experimental groups did not represent genetically separate Ae. aegypti populations. "
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    Journal of Medical Entomology 11/2011; 48(6):1095-102. DOI:10.1603/ME11129 · 1.95 Impact Factor
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    • "The global linkage disequilibrium (LD) profiles of the Ashkenazi Jewish (AJ) population do not seem to differ significantly from that of other populations of European ancestry. However, it has been suggested that there may be significant local differences in allele frequencies and haplotype structure between the Ashkenazi population and other European populations, including at loci associated with common cancer (Gold et al, 2008; Olshen et al, 2008; Price et al, 2008; Tian et al, 2008). Therefore, examination of known prostate cancer risk SNPs in the AJ population provides a unique opportunity to test for genetic heterogeneity at these loci among individuals of European ancestry. "
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    • "We also examined the BRCA2 mutation carriers in the instant study for significant F ST deviation in the BRCA1 region and found none. Finally, our previous work (Olshen et al. 2008) searched for evidence of long haplotypes throughout the genomes of randomly ascertained AJ and the HapMap CEU and found a similar pattern: extended haplotypes were absent, or present to a much lesser extent, in the CEU just like the CNJ in the present study. BRCA1 and BRCA2 founder mutations are observed at a higher frequency in Ashkenazi Jews compared to mutations in other populations. "
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