Variation of gene-based SNPs and linkage disequilibrium patterns in the human genome.
Variation of gene-based SNPs and linkage disequilibrium patterns in the human genome.
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人类基因组中基于基因的 SNP 的变异和连锁不平衡模式。
DOI：
10.1093/hmg/ddh177
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发表时间：
2004
影响因子：
3.5
通讯作者：
Yusuke Nakamura
中科院分区：
文献类型：
--
作者：
T. Tsunoda;G. Lathrop;A. Sekine;R. Yamada;A. Takahashi;Y. Ohnishi;Toshihiro Tanaka;Yusuke Nakamura
人类遗传学的一个主要目标是提供必要的工具，使全基因组关联研究。需要有关基因组中基于基因的单核苷酸多态性（SNP）和连锁不平衡（LD）模式分布的大量信息，以便选择标记来有效实施这种方法。为了获得这样的信息，我们对一个大型的日本队列进行了基因分型，通过对14000多个常染色体基因进行系统重测序确定了SNP。对这些数据的分析得出的结论是，日本人群包含约130 000种常见的常染色体基因单倍型（频率>0.05），其中超过35%在本研究中被鉴定。我们还根据基因内变异的位置及其在基因组中的分布检查了等位基因频率和LD模式。我们发现外显子SNP位点（非同义和同义）的等位基因变异性低于非外显子SNP位点，同一基因外显子内SNP之间的平均LD高于其他SNP组合，这两者都可能是选择的信号。LD与每物理距离的重组率相关，估计从减数分裂图，但在基因组的不同区域的关系的强度变化很大。独特的LD模式，其特征在于频繁的情况下，高LD之间的非相邻的SNPs打断低LD块，被发现在染色体6p上的7 Mb区域，包括MHC（主要组织相容性复合体）基因座和许多非MHC基因。这些结果表明，在考虑SNP变异性和LD模式时必须考虑的复杂性，同时也提供了实施有效的全基因组关联研究所需的工具。
A principal goal in human genetics is to provide the tools necessary to enable genome-wide association studies. Extensive information on the distribution of gene-based single-nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) patterns across the genome is required in order to choose markers for efficient implementation of this approach. To obtain such information, we have genotyped a large Japanese cohort for SNPs identified by systematic resequencing of more than 14 000 autosomal genes. Analysis of these data led to the conclusion that the Japanese population contains approximately 130 000 common autosomal gene haplotypes (frequency >0.05), of which more than 35% are identified in the present study. We also examined allele frequencies and LD patterns according to the position of variants within genes, and their distribution across the genome. We found lower allele variability at exonic SNP sites (both non-synonymous and synonymous) compared with non-exonic SNP sites, and greater average LD between SNPs within exons of the same gene compared with other SNP combinations, both of which could be signals of selection. LD was correlated with the recombination rate per physical distance as estimated from the meiotic map, but the strength of the relationship varied considerably in different regions of the genome. Unique LD patterns, characterized by frequent instances of high LD between non-adjacent SNPs punctuated by blocks of low LD, were found in a 7 Mb region on chromosome 6p that includes the MHC (major histocompatibility complex) locus and many non-MHC genes. These results demonstrate the complexity that must be taken into account when considering SNP variability and LD patterns, while also providing tools necessary for implementation of efficient genome-wide association studies.
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影响因子：
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