Use of a dense single nucleotide polymorphism map for in silico mapping in the mouse.
Use of a dense single nucleotide polymorphism map for in silico mapping in the mouse.
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DOI：
10.1371/journal.pbio.0020393
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发表时间：
2004-12
期刊：
影响因子：
9.8
通讯作者：
Wiltshire T
中科院分区：
文献类型：
--
作者：
Pletcher MT;McClurg P;Batalov S;Su AI;Barnes SW;Lagler E;Korstanje R;Wang X;Nusskern D;Bogue MA;Mural RJ;Paigen B;Wiltshire T
多品系小鼠的表型和基因型可用数据的快速扩展使得能够开发新的方法来询问小鼠基因组的功能遗传扰动。计算机作图提供了一种将表型性状的自然多样性与祖先遗传的多态性相关联的方便方法，以解剖遗传性状。在小鼠中，目前的单核苷酸多态性（SNP）数据缺乏整个基因组的密度和足够菌株的覆盖率，无法正确实现这一目标。为了补救这一点，在48个近交系小鼠品系中为10，990个均匀间隔的SNP基因座产生470，407个等位基因调用。使用的SNP集与统计模型，认为独特的模式内的块的三个SNP作为推断的单倍型可以成功地映射已知的单基因性状和克隆的数量性状基因。应用这种方法复制先前表征的数量性状位点（QTL）的高密度脂蛋白和胆结石表型。推断的单倍型数据还有助于QTL区域的细化，使得候选基因可以更容易地被鉴定和表征，如针对腺苷酸环化酶7所示。 大量的遗传标记资源，在48个品系的小鼠中进行分型，结合统计技术，允许“在计算机上”绘制涉及小鼠有趣性状的遗传区域
Rapid expansion of available data, both phenotypic and genotypic, for multiple strains of mice has enabled the development of new methods to interrogate the mouse genome for functional genetic perturbations. In silico mapping provides an expedient way to associate the natural diversity of phenotypic traits with ancestrally inherited polymorphisms for the purpose of dissecting genetic traits. In mouse, the current single nucleotide polymorphism (SNP) data have lacked the density across the genome and coverage of enough strains to properly achieve this goal. To remedy this, 470,407 allele calls were produced for 10,990 evenly spaced SNP loci across 48 inbred mouse strains. Use of the SNP set with statistical models that considered unique patterns within blocks of three SNPs as an inferred haplotype could successfully map known single gene traits and a cloned quantitative trait gene. Application of this method to high-density lipoprotein and gallstone phenotypes reproduced previously characterized quantitative trait loci (QTL). The inferred haplotype data also facilitates the refinement of QTL regions such that candidate genes can be more easily identified and characterized as shown for adenylate cyclase 7. A large resource of genetic markers, typed in 48 strains of mice, combined with statistical techniques, allow "in silico" mapping of genetic regions involved in interesting traits in mice
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影响因子：
6.5
作者：
Lyons, MA;Wittenburg, H;Paigen, B
通讯作者：
Paigen, B
影响因子：
30.8
作者：
Lindblad-Toh, K;Winchester, E;Lander, ES
通讯作者：
Lander, ES
影响因子：
3.5
作者：
Bachmanov, AA;Li, X;Beauchamp, GK
通讯作者：
Beauchamp, GK
影响因子：
15.9
作者：
Machleder, D;Ivandic, B;Lusis, AJ
通讯作者：
Lusis, AJ
影响因子：
56.9
作者：
Mural, RJ;Adams, MD;Venter, JC
通讯作者：
Venter, JC