Corticotropin releasing hormone (CRH) gene variation: comprehensive resequencing for variant and molecular haplotype discovery in monosomic hybrid cell lines.
Corticotropin releasing hormone (CRH) gene variation: comprehensive resequencing for variant and molecular haplotype discovery in monosomic hybrid cell lines.
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促肾上腺皮质激素释放激素 (CRH) 基因变异：单体杂交细胞系中变异和分子单倍型发现的综合重测序。
DOI：
10.1080/10425170701388719
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Hixson,JamesE
中科院分区：
文献类型：
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作者：
Shimmin,LawrenceC;Natarajan,Sivamani;Ibarguen,Heladio;Montasser,May;Kim,Do-Kyun;Hanis,CraigL;Boerwinkle,Eric;Wadhwa,PathikD;Hixson,JamesE
Candidate gene association studies have met with mixed success due to many reasons including incomplete surveys of genetic variation and differences in patterns of genetic variation among study populations. We present the results of comprehensive variant discovery for the corticotropin releasing hormone gene (CRHon chromosome 8) encoding a neuropeptide that is central to many physiologic pathways. Mouse–human hybrid cell lines were constructed that are monosomic for human chromosome 8 for resequencing of separated CRH alleles to identify variants and directly determine their chromosomal phase for three major ethnic groups including African Americans (AA), Mexican Americans (MA) and European Americans (EA). We also resequenced diploid individuals to evaluate single nucleotide polymorphism (SNP) discovery in the limited numbers of monosomic hybrid cell lines. Our results show that CRH variation is very different in AA, yielding larger numbers of variants and haplotypes compared to MA and EA. Analysis of LD structure found three haplotype blocks in AA and two blocks in EA. Comparisons between AA and EA groups yielded extremely high measures of genetic differentiation (Wright'sFST>0.6), likely reflecting disruptive selection in CRH evolution. Network analysis showed that AA have retained an ancestral CRH haplotype, while the most common EA haplotype is derived from a single recombination event.
