Browman K E, Crabbe J C
Portland Alcohol Research Center, Department of Veterans Affairs Medical Center and Department of Behavioral Neuroscience, Oregon Health Sciences University, 97201, USA.
Alcohol Clin Exp Res. 2000 Jan;24(1):17-23.
Genetic and environmental factors contribute to an individual's sensitivity to ethanol, although the exact genes underlying ethanol's effects are not known. Quantitative trait locus (QTL) mapping is one successful method for provisionally identifying genes participating in the mediation of a given behavior. QTL analyses seek to identify associations between a quantitative response and previously mapped marker genes across genetically diverse individuals. Many QTL analyses have been performed in BXD recombinant inbred (RI) strains of mice derived from a cross of C57BL/6J (B6) and DBA/2J (D2) progenitor strains.
We conducted a QTL analysis of ethanol-induced loss of righting reflex and ataxia using a panel of 25 BXD RI strains and the progenitors B6 and D2. We measured the duration of loss of righting reflex after injection and blood ethanol concentrations upon regaining of righting reflex. Ataxia was measured as the latency to fall from a vertical screen.
Genome-wide QTL analyses correlating strain means with allelic status at >1500 markers identified several associations (p < or = 0.01). These provisional QTLs were on all chromosomes except 2, 5, 12, 13, and X, and several map near potential candidate genes.
These results suggest that ethanol sensitivity is determined by the actions of multiple genes and further suggest their general chromosomal map locations. These provisional linkages will now be confirmed or rejected using additional genetically segregating populations.
遗传和环境因素会影响个体对乙醇的敏感性，尽管乙醇作用的确切基因尚不清楚。数量性状基因座（QTL）定位是一种成功的方法，可用于初步鉴定参与特定行为调节的基因。QTL分析旨在确定在遗传背景不同的个体中，定量反应与先前定位的标记基因之间的关联。许多QTL分析已在源自C57BL/6J（B6）和DBA/2J（D2）祖系杂交的BXD重组近交（RI）小鼠品系中进行。
我们使用一组25个BXD RI品系以及祖系B6和D2，对乙醇诱导的翻正反射丧失和共济失调进行了QTL分析。我们测量了注射后翻正反射丧失的持续时间以及翻正反射恢复时的血液乙醇浓度。共济失调通过从垂直屏幕上掉落的潜伏期来测量。
全基因组QTL分析将品系均值与>1500个标记处的等位基因状态相关联，确定了几个关联（p≤0.01）。这些初步的QTL位于除2、5、12、13和X染色体之外的所有染色体上，并且有几个位于潜在候选基因附近。
这些结果表明乙醇敏感性由多个基因的作用决定，并进一步表明了它们在染色体上的大致定位。现在将使用其他遗传分离群体来证实或否定这些初步的连锁关系。
