Phillips T J, Belknap J K, Buck K J, Cunningham C L
Veterans Administration Medical Center, R&D-32, 3710 SW US Veterans Hospital Rd., Portland, Oregon 97201, USA.
Mamm Genome. 1998 Dec;9(12):936-41. doi: 10.1007/s003359900903.
Quantitative trait locus (QTL) mapping efforts in alcohol (ethanol) research are beginning to generate promising data that may ultimately lead to the identification of genes influencing alcohol addiction. Rodents have been extensively utilized to study ethanol's rewarding and aversive effects, and to demonstrate the existence of genetic influences on traits such as free-choice ethanol-consumption, ethanol-conditioned place preference and ethanol-conditioned taste aversion. The purpose of the current investigation was to verify or eliminate from further consideration putative QTLs for free-choice ethanol consumption originally identified in BXD Recombinant Inbred (RI) strains and other informative genetic crosses. B6D2F2 mice were utilized in a verification testing strategy to evaluate the viability of putative ethanol consumption QTLs. When data were combined from BXD RI, B6D2F2 and short-term selected line (STSL) mapping studies, verification was obtained for two QTLs, one on Chromosome (Chr) 9 (proximal-mid) and another on Chr 2 (distal), and suggestive verification was obtained for QTLs on Chrs 2 (proximal), 3, 4, 7, and 15. In addition, the possible genetic association of ethanol consumption with conditioned place preference was evaluated. Genetic correlations were estimated from BXD RI strain means, and QTL maps for these traits were compared to evaluate the possibility of a genetic association. The correlational analysis yielded a trend (r = 0.34, p = 0.09), but no statistically significant results. However, comparisons of QTL mapping results between phenotypes suggested some possible genetic overlap for these traits, both putative measures of ethanol reward. These data suggest that the determinants of these two measures are genetically diverse, but may share some common genetic elements.
在酒精（乙醇）研究中，数量性状基因座（QTL）定位工作开始产生有前景的数据，这些数据最终可能会促成对影响酒精成瘾的基因的识别。啮齿动物已被广泛用于研究乙醇的奖赏和厌恶效应，并证明基因对诸如自由选择乙醇消耗、乙醇条件性位置偏爱和乙醇条件性味觉厌恶等性状存在影响。本研究的目的是对最初在BXD重组近交（RI）品系及其他信息丰富的遗传杂交中鉴定出的自由选择乙醇消耗的假定QTL进行验证，或在进一步研究中排除这些QTL。B6D2F2小鼠被用于验证测试策略，以评估假定的乙醇消耗QTL的可行性。当将BXD RI、B6D2F2和短期选择品系（STSL）定位研究的数据合并时，两个QTL得到了验证，一个位于第9号染色体（近端-中间），另一个位于第2号染色体（远端），并且在第2号染色体（近端）、第3、4、7和15号染色体上的QTL获得了提示性验证。此外，还评估了乙醇消耗与条件性位置偏爱的可能遗传关联。从BXD RI品系均值估计遗传相关性，并比较这些性状的QTL图谱以评估遗传关联的可能性。相关性分析得出一个趋势（r = 0.34，p = 0.09），但无统计学显著结果。然而，表型之间QTL定位结果的比较表明，这两个性状（均为乙醇奖赏的假定指标）可能存在一些共同的遗传重叠。这些数据表明，这两个指标的决定因素在遗传上是多样的，但可能共享一些共同的遗传元件。
