Foroud Tatiana, Ritchotte Aimee, Spence John, Liu Lixiang, Lumeng Lawrence, Li Ting-Kai, Carr Lucinda G
Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 West Walnut Street (IB-155), Indianapolis, IN 46202, USA.
Psychiatr Genet. 2003 Sep;13(3):155-61. doi: 10.1097/00041444-200309000-00004.
Selective breeding has been employed to develop replicate high-alcohol-drinking (HAD1 and HAD2) and low-alcohol-drinking (LAD1 and LAD2) rat lines from the heterogeneous N/Nih rat. Within-family selection and a rotational breeding design were used to discourage inbreeding (Li et al., 1993). A genome screen was previously performed using 459 HAD1xLAD1 F2 progeny to identify quantitative trait loci (QTLs) on rat chromosomes 5, 10, 12 and 16 that contribute to alcohol preference and consumption in these non-inbred rat models of alcoholism.
To confirm these QTLs in the replicate lines, 16 HAD2 and 16 LAD2 rats were genotyped for microsatellite markers within each of these QTL intervals.
Review of the genotypic data support confirmation of the QTLs on chromosomes 5 and 10; several markers in the QTL region display different alleles in the HAD2 and LAD2 rats, suggesting linkage disequilibrium between the microsatellite markers and the QTL. Although the QTL on chromosome 12 had the highest LOD score in the HAD1 and LAD1 studies, little evidence supported confirmation of this QTL based on the genotyped markers.
Further evaluation of each of these QTL regions is ongoing in a sample of HAD2xLAD2 F2 progeny currently being generated that will be used to assess the evidence of linkage in each of these QTL regions.
已采用选择性育种从异质N/Nih大鼠培育出高饮酒量（HAD1和HAD2）和低饮酒量（LAD1和LAD2）的复制大鼠品系。采用家系内选择和轮回育种设计以防止近亲繁殖（Li等人，1993年）。先前使用459只HAD1×LAD1 F2后代进行了基因组筛选，以鉴定大鼠5号、10号、12号和16号染色体上的数量性状基因座（QTL），这些基因座在这些非近亲繁殖的酒精中毒大鼠模型中影响酒精偏好和摄入量。
为了在复制品系中确认这些QTL，对16只HAD2和16只LAD2大鼠在每个这些QTL区间内的微卫星标记进行基因分型。
对基因型数据的审查支持确认5号和10号染色体上的QTL；QTL区域中的几个标记在HAD2和LAD2大鼠中显示出不同的等位基因，表明微卫星标记与QTL之间存在连锁不平衡。尽管在HAD1和LAD1研究中12号染色体上的QTL具有最高的LOD分数，但基于基因分型标记几乎没有证据支持确认该QTL。
目前正在对一组HAD2×LAD2 F2后代样本中的每个这些QTL区域进行进一步评估，这些后代将用于评估每个这些QTL区域中的连锁证据。
