Genomewide SNP Screen to Detect Quantitative Trait Loci for Alcohol Preference in the High Alcohol Preferring and Low Alcohol Preferring Mice
Genomewide SNP Screen to Detect Quantitative Trait Loci for Alcohol Preference in the High Alcohol Preferring and Low Alcohol Preferring Mice
复制标题
DOI：
10.1111/j.1530-0277.2008.00866.x
复制
发表时间：
2009-03-01
影响因子：
3.2
通讯作者：
Foroud, Tatiana
中科院分区：
文献类型：
--
作者：
Bice, Paula;Valdar, William;Foroud, Tatiana
高和低酒精偏好（HAP 1和LAP 1）小鼠系选择性地繁殖酒精摄入量的差异。HAP 1和LAP 1小鼠基本上都是非近交系，它们来源于HS/Ibg小鼠的远交群体，HS/Ibg小鼠是由8个近交系小鼠杂交而成的异质群体（6个LAP 1，8个HAP 1），以及8个杂交产生HS/Ibg集落的近交系小鼠。进行多点全基因组分析以同时检测连锁的QTL，并使用祖先单倍型精细定位这些区域。QTL分析在4条染色体上检测到显著的关联证据：1，3，5和9。之前使用全基因组微卫星筛选发现9号染色体上的区域在这些F2动物的一个子集中连锁。我们已经检测到与小鼠多个染色体区域相关的强有力证据。其中几个区域包括先前与人类或其他动物模型中的酒精依赖相关的候选基因。
The high and low alcohol preferring (HAP1 and LAP1) mouse lines were selectively bred for differences in alcohol intake. The HAP1 and LAP1 mice are essentially noninbred lines that originated from the outbred colony of HS/Ibg mice, a heterogeneous stock developed from intercrossing 8 inbred strains of mice.A total of 867 informative SNPs were genotyped in 989 HAP1 x LAP1 F2, 68 F1s, 14 parents (6 LAP1, 8 HAP1), as well as the 8 inbred strains of mice crossed to generate the HS/Ibg colony. Multipoint genome wide analyses were performed to simultaneously detect linked QTLs and also fine map these regions using the ancestral haplotypes.QTL analysis detected significant evidence of association on 4 chromosomes: 1, 3, 5, and 9. The region on chromosome 9 was previously found linked in a subset of these F2 animals using a whole genome microsatellite screen.We have detected strong evidence of association to multiple chromosomal regions in the mouse. Several of these regions include candidate genes previously associated with alcohol dependence in humans or other animal models.