Quantitative trait locus mapping of acute functional tolerance in the LXS recombinant inbred strains.
Quantitative trait locus mapping of acute functional tolerance in the LXS recombinant inbred strains.
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DOI：
10.1111/acer.12678
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Radcliffe RA
中科院分区：
文献类型：
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作者：
Bennett B;Larson C;Richmond PA;Odell AT;Saba LM;Tabakoff B;Dowell R;Radcliffe RA
我们以前曾报道，急性功能耐受（AFT）的酒精催眠作用是显着相关的LXS RI面板中的黑暗中饮酒（DID），但只有在小鼠已经用酒精预处理。在这里，我们进行了QTL定位AFT。还进行了祖先ILS和ISS菌株的DNA测序和微阵列分析以鉴定候选基因和功能相关性。在第一天给予LXS小鼠盐水或酒精（5g/kg），然后在第二天AFT测试翻正反射（LORR）的丧失。使用标准程序定位QTL。对脑进行了两次微阵列分析：1）未经处理的LXS小鼠和2）ILS和ISS中的酒精处理时间过程。对ILS和ISS的全基因组进行测序，深度约为30×。一个显着的QTL AFT在酒精预处理组定位到远端4号染色体，许多暗示QTL也被映射。饮酒偏好和DID先前已被定位到4号染色体位点。显著的4号染色体QTL的可信区间跨越23 Mb，包括716个注释的基因，其中150个具有至少一个非同义SNP或小indel，在ILS和ISS之间不同; 48个基因的表达是顺式调节的。富集分析表明，广泛的功能类别AFT包括蛋白水解，转录调节，染色质修饰，蛋白激酶活性，细胞凋亡，和其他。第4染色体QTL是控制AFT和饮酒行为的一个关键区域，可能含有多效基因。考虑到该区域包含许多可行的候选基因，并且该区间中的大量基因属于一个或多个丰富的功能类别，我们假设许多效应大小不同的基因有助于观察到的QTL效应。
We previously reported that acute functional tolerance (AFT) to the hypnotic effects of alcohol was significantly correlated to drinking in the dark (DID) in the LXS RI panel, but only in mice that had been pretreated with alcohol. Here we have conducted QTL mapping for AFT. DNA sequencing of the progenitor ILS and ISS strains and microarray analyses were also conducted to identify candidate genes and functional correlates. LXS mice were given either saline or alcohol (5 g/kg) on day one and then tested for loss of righting reflex (LORR) AFT on day two. QTLs were mapped using standard procedures. Two microarray analyses from brain were conducted: 1) naïve LXS mice and 2) an alcohol treatment time course in the ILS and ISS. The full genomes of the ILS and ISS were sequenced to a depth of ~30×. A significant QTL for AFT in the alcohol pretreatment group mapped to distal chromosome 4; numerous suggestive QTLs were also mapped. Preference drinking and DID have previously been mapped to the chromosome 4 locus. The credible interval of the significant chromosome 4 QTL spanned 23 Mb and included 716 annotated genes of which 150 had at least one non-synonymous SNP or small indel that differed between the ILS and ISS; expression of 48 of the genes was cis-regulated. Enrichment analysis indicated broad functional categories underlying AFT including proteolysis, transcription regulation, chromatin modification, protein kinase activity, apoptosis, and others. The chromosome 4 QTL is a key region containing possibly pleiotropic genes for AFT and drinking behavior. Given that the region contains many viable candidates and a large number of the genes in the interval fall into one or more of the enriched functional categories, we postulate that many genes of varying effect size contribute to the observed QTL effect.
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影响因子：
2.6
作者：
Bennett, Beth;Saba, Laura M.;Hornbaker, Cheryl K.;Kechris, Katerina J.;Hoffman, Paula;Tabakoff, Boris
通讯作者：
Tabakoff, Boris
影响因子：
6.7
作者：
Dick, Danielle M;Bierut, Laura J
通讯作者：
Bierut, Laura J
影响因子：
5.8
作者：
Hubbell, E;Liu, WM;Mei, R
通讯作者：
Mei, R
DOI：
10.1111/acer.12465
发表时间：
2014-07
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Finegersh A;Homanics GE
通讯作者：
Homanics GE
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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