Analysis of genetic variation in Ashkenazi Jews by high density SNP genotyping
Analysis of genetic variation in Ashkenazi Jews by high density SNP genotyping
复制标题
DOI：
10.1186/1471-2156-9-14
复制
发表时间：
2008-02-05
期刊：
影响因子：
2.9
通讯作者：
Boyd, Jeff
中科院分区：
文献类型：
--
作者：
Olshen, Adam B.;Gold, Bert;Boyd, Jeff
背景资料：遗传分离株，如德系犹太人（AJ）可能提供的优势，在全基因组疾病关联研究中绘制新的基因座。为了分析AJ中的遗传变异模式，使用AffysseEAv 3 500 K SNP阵列确定101名健康个体的基因型，并与60名CEPH衍生的HapMap（CEU）个体进行比较。结果：AJ和CEU之间等位基因频率的平均F-ST值为0.009（P < 0.001），表明AJ和CEU之间等位基因频率存在微小但显著的总体差异;在2号和6号染色体上发现了较大的差异区域。从成对连锁不平衡（LD）统计（Haploview）以及通过期望最大化单倍型相位推断（HAP）推断的单倍型块显示，与通过Haploview（50，397对44，169）或通过HAP（59，269对54，457）的CEU相比，AJ中的单倍型块的数量更大。AJ的平均单倍型块小于CEU（e.例如，在一个实施例中，36.8 kb对40.5kb HAP）。对CEU中紧密间隔的SNP的局部LD衰减的全球模式的分析表明更多的LD，而对于相距较远的SNP，LD在AJ中略大。似然比方法表明，纯合SNP的运行时间约为20%，在AJ。主成分分析是足以完全解决的CEU从AJ.Conclusion：LD在AJ与低于预期的一些措施和更高的其他。任何推定的优势，在全基因组关联作图使用AJ人口将高度依赖于区域LD结构。
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.