Horvat S, Medrano J F
Department of Animal Science, University of California, Davis 95616-8521, USA.
Genetics. 1995 Apr;139(4):1737-48. doi: 10.1093/genetics/139.4.1737.
The high growth locus (hg) causes a major increase in weight gain and body size in mice. As a first step to map-based cloning of hg, we developed a genetic map of the hg-containing region using interval mapping of 403 F2 from a C57BL/6J-hghg x CAST/EiJ cross. The maximum likelihood position of hg was at the chromosome 10 marker D10Mit41 (LOD = 24.8) in the F2 females and 1.5 cM distal to D10Mit41 (LOD = 9.56) in the F2 males with corresponding LOD 2 support intervals of 3.7 and 5.4 cM, respectively. The peak LOD scores were significantly higher than the estimated empirical threshold LOD values. The localization of hg by interval mapping was supported by a test cross of F2 mice recombinant between the LOD 2 support interval and the flanking marker. The interval mapping and test-cross results indicate that hg is not allelic with candidate genes Igf1 or decorin (Dcn), a gene that was mapped close to hg in this study. The hg inheritance was recessive in females, although we could not reject recessive or additive inheritance in males. Possible causes for sex differences in peak LOD scores and for the distortion of transmission ratios observed in F2 males are discussed. The genetic map of the hg region will facilitate further fine mapping and cloning of hg, and allow searches for a homologous quantitative trait locus affecting growth in humans and domestic animals.
高生长位点(hg)可使小鼠的体重增加和体型显著增大。作为基于图谱克隆hg的第一步,我们利用来自C57BL/6J-hghg×CAST/EiJ杂交的403只F2小鼠进行区间定位,构建了包含hg区域的遗传图谱。在F2雌性小鼠中,hg的最大似然位置位于10号染色体标记D10Mit41处(LOD = 24.8),在F2雄性小鼠中位于D10Mit41远端1.5 cM处(LOD = 9.56),相应的LOD 2支持区间分别为3.7 cM和5.4 cM。峰值LOD分数显著高于估计的经验阈值LOD值。通过对在LOD 2支持区间和侧翼标记之间重组的F2小鼠进行测交,支持了通过区间定位对hg的定位。区间定位和测交结果表明,hg与候选基因Igf1或核心蛋白聚糖(Dcn,在本研究中定位在靠近hg的位置)不是等位基因。hg的遗传在雌性中是隐性的,尽管我们不能排除在雄性中是隐性或加性遗传。文中讨论了峰值LOD分数性别差异以及在F2雄性中观察到的传递率扭曲的可能原因。hg区域的遗传图谱将有助于进一步对hg进行精细定位和克隆,并有助于寻找影响人类和家畜生长的同源数量性状位点。