Jackson A U, Fornés A, Galecki A, Miller R A, Burke D T
Department of Human Genetics, Ann Arbor, Michigan 48109, USA.
Genetics. 1999 Feb;151(2):785-95. doi: 10.1093/genetics/151.2.785.
Quantitative trait loci influencing several phenotypes were assessed using a genetically heterogeneous mouse population. The 145 individuals were produced by a cross between (BALB/cJ x C57BL/6J)F1 females and (C3H/HeJ x DBA/2J)F1 males. The population is genetically equivalent to full siblings derived from heterozygous parents, with known linkage phase. Each individual in the population represents a unique combination of alleles from the inbred grandparents. Quantitative phenotypes for eight T cell measures were obtained at 8 and 18 mo of age. Single-marker locus, repeated measures analysis of variance identified nine marker-phenotype associations with an experimentwise significance level of P < 0.05. Six of the eight quantitative phenotypes could be associated with at least one locus having experiment-wide significance. Composite interval, repeated measures analysis of variance identified 13 chromosomal regions with comparisonwise (nominal) significance associations of P < 0.001. The heterozygous-parent cross provides a reproducible, general method for identification of loci associated with quantitative trait phenotypes or repeated phenotypic measures.
利用遗传异质性小鼠群体评估了影响多种表型的数量性状基因座。这145只个体由(BALB/cJ×C57BL/6J)F1雌性与(C3H/HeJ×DBA/2J)F1雄性杂交产生。该群体在遗传上等同于来自杂合亲本的全同胞,具有已知的连锁相。群体中的每个个体都代表了来自近交祖父母等位基因的独特组合。在8月龄和18月龄时获得了八项T细胞指标的定量表型。单标记基因座重复测量方差分析确定了九个标记-表型关联,实验显著性水平为P<0.05。八项定量表型中的六项可与至少一个具有全实验显著性的基因座相关联。复合区间重复测量方差分析确定了13个染色体区域,其比较(名义)显著性关联为P<0.001。杂合亲本杂交提供了一种可重复的通用方法,用于鉴定与数量性状表型或重复表型测量相关的基因座。