Segregation of a QTL cluster for home-cage activity using a new mapping method based on regression analysis of congenic mouse strains

Recent genetic studies have shown that genetic loci with significant effects in whole-genome quantitative trait loci (QTL) analyses were lost or weakened in congenic strains. Characterisation of the genetic basis of this attenuated QTL effect is important to our understanding of the genetic mechanisms of complex traits. We previously found that a consomic strain, B6-Chr6CMSM, which carries chromosome 6 of a wild-derived strain MSM/Ms on the genetic background of C57BL/6J, exhibited lower home-cage activity than C57BL/6J. In the present study, we conducted a composite interval QTL analysis using the F2 mice derived from a cross between C57BL/6J and B6-Chr6CMSM. We found one QTL peak that spans 17.6 Mbp of chromosome 6. A subconsomic strain that covers the entire QTL region also showed lower home-cage activity at the same level as the consomic strain. We developed 15 congenic strains, each of which carries a shorter MSM/Ms-derived chromosomal segment from the subconsomic strain. Given tha...近期的遗传学研究表明，在全基因组数量性状位点（quantitative trait loci, QTL）分析中具有显著效应的遗传基因座，在同源导入系（congenic strains）中会出现效应丢失或减弱的情况。解析这种减弱的QTL效应的遗传基础，有助于我们理解复杂性状的遗传调控机制。本课题组此前发现，在C57BL/6J的遗传背景（genetic background）下携带野生来源近交系（wild-derived strain）MSM/Ms的6号染色体的染色体替换系（consomic strain）B6-Chr6CMSM，其笼内自发活动量（home-cage activity）低于C57BL/6J品系。在本研究中，我们利用C57BL/6J与B6-Chr6CMSM杂交获得的F2代小鼠（F2 mice）开展了复合区间QTL分析（composite interval QTL analysis）。我们在6号染色体上检测到一个跨度为17.6百万碱基对（Mbp）的QTL峰。覆盖该QTL全区域的亚染色体替换系（subconsomic strain），同样展现出与染色体替换系相当的低笼内自发活动水平。我们从该亚染色体替换系中构建了15个同源导入系，每个品系均携带一段更短的MSM/Ms来源染色体片段。鉴于……