Fine-mapping of muscle weight QTL in LG/J and SM/J intercrosses
Fine-mapping of muscle weight QTL in LG/J and SM/J intercrosses
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DOI：
10.1152/physiolgenomics.00100.2010
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发表时间：
2010-09-01
影响因子：
4.6
通讯作者：
Blizard, D. A.
中科院分区：
文献类型：
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作者：
Lionikas, A.;Cheng, R.;Blizard, D. A.
Lionikas A、Cheng R、Lim JE、Palmer AA、Blizard DA。 LG/J 和 SM/J 杂交中肌肉重量 QTL 的精细定位。 Physiol Genomics 42A: 33-38, 2010。首次发表于 2010 年 7 月 13 日； doi:10.1152/physicalgenomics.00100.2010.-遗传变异在力量变化中发挥着重要作用，但其潜在机制仍知之甚少。本研究的目的是检查 LG/J 和 SM/J 品系之间肌肉质量（力量的预测因子）变化的机制，这两个品系分别是选择高体重和低体重小鼠的近交后代。我们测量了 LG/J 和 SM/J 雄性和雌性、F(1) 和 F(2) 杂交以及两者之间的高级杂交 (AI)、F(34) 中五块后肢肌肉的重量。使用整个基因组中的 162 个 SNP 对 F(2) 小鼠进行基因分型； F(34) 小鼠的 3,015 个 SNP 进行了基因分型。观察到 LG/J 和 SM/J 小鼠品系的肌肉质量存在两倍差异。 F(2) 和 AI 组合群体中的综合全基因组关联分析确定了影响 Chr 2 (2 QTL)、4、5、6 (7 QTL)、7 (4 QTL)、8 (4 QTL) 和 11 (3 QTL) 肌肉重量的 22 个数量性状位点 (QTL；全基因组 P < 0.05)。在所有情况下，LG/J 等位基因都赋予更大的肌肉重量。 1.5-LOD QTL 支持区间范围为 0.3 至 13.4 Mb（中位数 3.7 Mb），将候选基因列表限制在 5 至 97 个基因之间。体重选择分离了影响骨骼肌（体内最丰富的组织）的等位基因。 F(2) 和 AI 分析的组合是在全基因组范围内检测和细化 QTL 的有效策略。所达到的分辨率有助于进一步阐明影响肌肉质量的潜在遗传机制。
Lionikas A, Cheng R, Lim JE, Palmer AA, Blizard DA. Finemapping of muscle weight QTL in LG/J and SM/J intercrosses. Physiol Genomics 42A: 33-38, 2010. First published July 13, 2010; doi:10.1152/physiolgenomics.00100.2010.-Genetic variation plays a substantial role in variation in strength, but the underlying mechanisms remain poorly understood. The objective of the present study was to examine the mechanisms underlying variation in muscle mass, a predictor of strength, between LG/J and SM/J strains, which are the inbred progeny of mice selected, respectively, for high and low body weight. We measured weight of five hindlimb muscles in LG/J and SM/J males and females, in F(1) and F(2) intercrosses, and in an advanced intercross (AI), F(34), between the two. F(2) mice were genotyped using 162 SNPs throughout the genome; F(34) mice were genotyped at 3,015 SNPs. A twofold difference in muscle mass between the LG/J and SM/J mouse strains was observed. Integrated genome-wide association analysis in the combined population of F(2) and AI identified 22 quantitative trait loci (QTL; genome-wide P < 0.05) affecting muscle weight on Chr 2 (2 QTL), 4, 5, 6 (7 QTL), 7 (4 QTL), 8 (4 QTL), and 11 (3 QTL). The LG/J allele conferred greater muscle weight in all cases. The 1.5-LOD QTL support intervals ranged between 0.3 and 13.4 Mb (median 3.7 Mb) restricting the list of candidates to between 5 and 97 genes. Selection for body weight segregated the alleles affecting skeletal muscle, the most abundant tissue in the body. Combination of analyses in an F(2) and AI was an effective strategy to detect and refine the QTL in a genome-wide manner. The achieved resolution facilitates further elucidation of the underlying genetic mechanisms affecting muscle mass.