Bice P, Foroud T, Bo R, Castelluccio P, Lumeng L, Li T K, Carr L G
Department of Medicine, Indiana University School of Medicine, Medical Research and Library Building, Room 407, 975 W. Walnut Street, Indianapolis, Indiana 46202, USA.
Mamm Genome. 1998 Dec;9(12):949-55. doi: 10.1007/s003359900905.
Selective breeding for voluntary alcohol consumption was utilized to establish the alcohol-preferring (P) and alcohol-nonpreferring (NP) rat lines. Inbreeding was initiated after 30 generations of selection and, after 19 generations of inbreeding, 384 F2 intercross progeny were created to identify quantitative trait loci (QTLs) influencing alcohol consumption. We had reported previously a QTL on Chromosome (Chr) 4; additional markers genotyped on Chr 4 have increased the maximum lod score from 8.6 to 9.2. This QTL acts in an additive fashion and continues to account for approximately 11% of the phenotypic variability. The 95% confidence interval is 12.5 cM and includes the candidate gene, neuropeptide Y. Subsequent to the identification of the QTL on Chr 4, a genome scan was completed to identify additional QTLs influencing alcohol consumption. A lod score of 2.5 was obtained on Chr 3, syntenic to a region previously reported for alcohol preference in mice. Analysis of Chr 8 produced a lod score of 2.2 near the dopamine D2 and serotonin 1b receptors, which have been previously reported as candidate genes for alcohol preference. Evidence for linkage to alcohol consumption was not found on any other chromosome. It therefore appears likely that, in addition to the QTL on Chr 4, multiple loci of small to moderate effect, such as those on Chrs 3 and 8, underlie the difference in alcohol consumption in the P/NP lines.
通过对自愿饮酒进行选择性育种，建立了嗜酒（P）和不嗜酒（NP）大鼠品系。在经过30代选择后开始近亲繁殖，经过19代近亲繁殖后，产生了384只F2代杂交后代，以确定影响酒精摄入量的数量性状基因座（QTL）。我们之前报道过4号染色体上存在一个QTL；在4号染色体上进行基因分型的其他标记已将最大对数得分从8.6提高到9.2。这个QTL以加性方式起作用，并且继续解释约11%的表型变异。95%的置信区间为12.5厘摩，包含候选基因神经肽Y。在确定4号染色体上的QTL之后，完成了全基因组扫描以确定影响酒精摄入量的其他QTL。在3号染色体上获得了2.5的对数得分，该区域与之前报道的小鼠酒精偏好区域同线。对8号染色体的分析在多巴胺D2和5-羟色胺1b受体附近产生了2.2的对数得分，这两个受体之前已被报道为酒精偏好的候选基因。在任何其他染色体上均未发现与酒精摄入量相关的证据。因此，除了4号染色体上的QTL外，可能还有多个效应大小从中等到较小的基因座，如3号和8号染色体上的那些基因座，构成了P/NP品系中酒精摄入量差异的基础。
