Genomic screen for QTLs underlying alcohol consumption in the P and NP rat lines
Genomic screen for QTLs underlying alcohol consumption in the P and NP rat lines
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DOI：
10.1007/s003359900905
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发表时间：
1998-12-01
期刊：
影响因子：
2.5
通讯作者：
Carr, LG
中科院分区：
文献类型：
--
作者：
Bice, P;Foroud, T;Carr, LG
利用自愿饮酒的选择性育种建立了酒精偏好（P）和酒精非偏好（UP）大鼠品系。选择30代后开始近交，近交19代后，产生384个F-2互交后代，以确定影响酒精消费量的数量性状位点（QTL）。我们以前曾报道染色体（Chr）4上的QTL;在Chr 4上基因分型的其他标记使最大LOD分数从8.6增加到9.2。该QTL以加性方式起作用，并继续占表型变异的约11%。95%置信区间为12.5 cM，包括候选基因神经肽Y。在鉴定了Chr 4上的QTL之后，完成了基因组扫描以鉴定影响酒精消耗的其他QTL。在Chr 3上获得了2.5的lod评分，与先前报道的小鼠酒精偏好的区域同线。对Chr 8的分析在多巴胺D2和5-羟色胺Ib受体附近产生了2.2的lod评分，这些受体以前曾被报道为酒精偏好的候选基因。在其他任何染色体上都没有发现与饮酒有关的证据。因此，除了第4染色体上的QTL外，多个小到中等效应的基因座，如第3和第8染色体上的基因座，可能是P/NP系中酒精消耗差异的基础。
Selective breeding for voluntary alcohol consumption was utilized to establish the alcohol-preferring (P) and alcohol-nonpreferring (UP) rat lines. Inbreeding was initiated after 30 generations of selection and, after 19 generations of inbreeding, 384 F-2 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 Ib 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.