A major QTL for acute ethanol sensitivity in the alcohol tolerant and non-tolerant selected rat lines.

A major QTL for acute ethanol sensitivity in the alcohol tolerant and non-tolerant selected rat lines.
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DOI:
10.1111/j.1601-183x.2009.00496.x
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发表时间:
2009-08
期刊:
Genes, brain, and behavior
影响因子:
--
通讯作者:
Deitrich RA
Deitrich RA
中科院分区:
其他
文献类型:
--
作者:
Radcliffe RA;Erwin VG;Bludeau P;Deng X;Fay T;Floyd KL;Deitrich RA

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酒精耐受和酒精非耐受大鼠(AT,ANT)选择性饲养乙醇诱导的共济失调,在斜面上测量。在这里,我们报告了一个数量性状位点(QTL)的研究在F2的自交系AT和ANT(IAT,IANT)和后续研究的同源系,培育检查的QTL之一。对1200多只F2代子代进行了斜面敏感性、斜面急性耐受性、翻正反射丧失持续时间(LORR)和翻正反射恢复时血液乙醇含量(BECRR)测试。对斜面敏感性处于上20%和下20%的F2大鼠用78个SSLP标记物进行基因分型。斜面敏感性的显着QTL定位在第8和20染色体上,暗示性QTL定位在第1,2和3染色体上。LORR持续时间(LOD=12.4)和BECRR(LOD=5.7)的高显着QTL定位到同一个位点上的1号染色体。通过正反交同源系的选育和检测,证实了1号染色体LORR/BECRR QTL的存在。培育了一系列重组同源亚系来精细定位该QTL。目前的结果已经将QTL缩小到5和20 Mb之间的区间。我们希望能够缩小间隔小于5 Mb的额外的基因分型和继续育种的重组亚同源系。
The Alcohol Tolerant and Alcohol Non-Tolerant rats (AT, ANT) were selectively bred for ethanol-induced ataxia as measured on the inclined plane. Here we report on a quantitative trait locus (QTL) study in an F2 intercross population derived from inbred AT and ANT (IAT, IANT) and a follow-up study of congenics that were bred to examine one of the mapped QTLs. Over 1200 F2 offspring were tested for inclined plane sensitivity, acute tolerance on the inclined plane, duration of the loss of righting reflex (LORR), and blood ethanol at regain of the righting reflex (BECRR). F2 rats that were in the upper and lower 20% for inclined plane sensitivity were genotyped with 78 SSLP markers. Significant QTLs for inclined plane sensitivity were mapped on chromosomes 8 and 20; suggestive QTLs were mapped on chromosomes 1, 2, and 3. Highly significant QTLs for LORR duration (LOD=12.4) and BECRR (LOD=5.7) were mapped to the same locus on chromosome 1. Breeding and testing of reciprocal congenic lines confirmed the chromosome 1 LORR/BECRR QTL. A series of recombinant congenic sub-lines were bred to fine-map this QTL. Current results have narrowed the QTL to an interval of between 5 and 20 Mb. We expect to be able to narrow the interval to less than 5 Mb with additional genotyping and continued breeding of recombinant sub-congenic lines.