Integration of QTL and bioinformatic tools to identify candidate genes for triglycerides in mice
Integration of QTL and bioinformatic tools to identify candidate genes for triglycerides in mice
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DOI：
10.1194/jlr.m011130
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发表时间：
2011-09-01
影响因子：
6.5
通讯作者：
Paigen, Beverly
中科院分区：
文献类型：
--
作者：
Leduc, Magalie S.;Hageman, Rachael S.;Paigen, Beverly
为了确定影响血脂水平的遗传位点，我们在近交系小鼠MRL/MPJ和SM/J之间进行了数量性状基因座(QTL)分析，测量了8周龄饲喂饲料的F2小鼠的甘油三酯水平。我们在染色体(Chr)15上定位了1个显著的QTL，并在CHRS 2、7和17上发现了3个建议的QTL。我们还对282 F2小鼠亲本的肝脏进行了基因芯片分析，并利用这些数据寻找了顺式调控的表达QTL。然后，我们使用生物信息学资源的“工具箱”缩小了显著QTL下的候选基因列表，包括单倍型分析；双亲菌株基因表达差异和非同义编码单核苷酸多态(SNP)的比较；F2小鼠肝脏中顺式调控的eQTL；基因表达和表型之间的相关性；以及表达对表型的调节。我们建议将Slc25a7作为Chr7 QTL的候选基因，并根据表达差异确定5个基因(Polr3h、Cyp2d22、Cyp2d26、Tspo和Ttll12)作为Chr15 QTL的候选基因。这项研究展示了如何有效地利用生物信息学来减少与复杂性状相关的QTL候选基因列表。-Leduc，M.S.，R.S.Hageman，R.A.Verdugo，S-W.首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细内容整合QTL和生物信息学工具以确定小鼠甘油三酯的候选基因。J.Lipid Res.2011年。52：1672-1682。
To identify genetic loci influencing lipid levels, we performed quantitative trait loci (QTL) analysis between inbred mouse strains MRL/MpJ and SM/J, measuring triglyceride levels at 8 weeks of age in F2 mice fed a chow diet. We identified one significant QTL on chromosome (Chr) 15 and three suggestive QTL on Chrs 2, 7, and 17. We also carried out microarray analysis on the livers of parental strains of 282 F2 mice and used these data to find cis-regulated expression QTL. We then narrowed the list of candidate genes under significant QTL using a "toolbox" of bioinformatic resources, including haplotype analysis; parental strain comparison for gene expression differences and nonsynonymous coding single nucleotide polymorphisms (SNP); cis-regulated eQTL in livers of F2 mice; correlation between gene expression and phenotype; and conditioning of expression on the phenotype. We suggest Slc25a7 as a candidate gene for the Chr 7 QTL and, based on expression differences, five genes (Polr3 h, Cyp2d22, Cyp2d26, Tspo, and Ttll12) as candidate genes for Chr 15 QTL. This study shows how bioinformatics can be used effectively to reduce candidate gene lists for QTL related to complex traits.-Leduc, M. S., R. S. Hageman, R. A. Verdugo, S-W. Tsaih, K. Walsh, G. A. Churchill, and B. Paigen. Integration of QTL and bioinformatic tools to identify candidate genes for triglycerides in mice. J. Lipid Res. 2011. 52: 1672-1682.