Trachtulec Zdenek, Vlcek Cestmir, Mihola Ondrej, Gregorova Sona, Fotopulosova Vladana, Forejt Jiri
Department of Mouse Molecular Genetics, Institute of Molecular Genetics Academy of Sciences of the Czech Republic, 14220 Prague, Czech Republic.
Genetics. 2008 Mar;178(3):1777-84. doi: 10.1534/genetics.107.082404. Epub 2008 Feb 3.
Extensive linkage disequilibrium among classical laboratory strains represents an obstacle in the high-resolution haplotype mapping of mouse quantitative trait loci (QTL). To determine the potential of wild-derived mouse strains for fine QTL mapping, we constructed a haplotype map of a 250-kb region of the t-complex on chromosome 17 containing the Hybrid sterility 1 (Hst1) gene. We resequenced 33 loci from up to 80 chromosomes of five mouse (sub)species. Trans-species single-nucleotide polymorphisms (SNPs) were rare between Mus m. musculus (Mmmu) and Mus m. domesticus (Mmd). The haplotypes in Mmmu and Mmd differed and therefore strains from these subspecies should not be combined for haplotype-associated mapping. The haplotypes of t-chromosomes differed from all non-t Mmmu and Mmd haplotypes. Half of the SNPs and SN indels but only one of seven longer rearrangements found in classical laboratory strains were useful for haplotype mapping in the wild-derived M. m. domesticus. The largest Mmd haplotype block contained three genes of a highly conserved synteny. The lengths of the haplotype blocks deduced from 36 domesticus chromosomes were in tens of kilobases, suggesting that the wild-derived Mmd strains are suitable for fine interval-specific mapping.
经典实验室品系间广泛的连锁不平衡是小鼠数量性状基因座(QTL)高分辨率单倍型图谱绘制中的一个障碍。为了确定野生来源小鼠品系在精细QTL图谱绘制中的潜力,我们构建了17号染色体t复合体上一个250 kb区域的单倍型图谱,该区域包含杂种不育1(Hst1)基因。我们对来自五个小鼠(亚)种的多达80条染色体上的33个位点进行了重测序。小家鼠(Mus m. musculus,Mmmu)和家鼠(Mus m. domesticus,Mmd)之间的跨物种单核苷酸多态性(SNP)很少见。Mmmu和Mmd中的单倍型不同,因此来自这些亚种的品系不应合并用于单倍型关联图谱绘制。t染色体的单倍型与所有非t的Mmmu和Mmd单倍型不同。经典实验室品系中发现的一半SNP和SN插入缺失,但七个较长重排中只有一个对野生来源小家鼠的单倍型图谱绘制有用。最大的Mmd单倍型块包含一个高度保守同线性的三个基因。从36条家鼠染色体推导的单倍型块长度在几十千碱基,这表明野生来源的Mmd品系适用于精细的区间特异性图谱绘制。
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