Cis-acting expression quantitative trait loci in mice
Cis-acting expression quantitative trait loci in mice
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DOI：
10.1101/gr.3216905
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发表时间：
2005-05-01
期刊：
影响因子：
7
通讯作者：
Lusis, AJ
中科院分区：
文献类型：
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作者：
Doss, S;Schadt, EE;Lusis, AJ
我们之前报道了近交系小鼠品系 C57BL/6J (B6) 和 DBA/2J (DBA) 分离杂交中全基因组表达谱和各种糖尿病相关性状的分析。通过将转录水平视为数量性状，我们确定了数千个 LOD 得分 > 4.3 的表达数量性状位点 [eQTL]。我们现在通过估计顺式作用调控下的假阳性 eQTL 的比例来通过实验解决多重比较的问题。为此，我们利用了 (B6 x DBA)F-1 rilice 的经典顺反测试来确定 B6 和 DBA 等位基因转录物的相对水平。结果表明，至少 64% 的 LOD > 4.3 的顺式作用 eQTL 为真阳性，而其余 36% 不能被确认为真正的顺式作用。此外，我们发现 > 96% 的明显顺式作用 eQTL 出现在不共享 SNP 单倍型的患病区域。顺式作用 eQTL 是鉴定小鼠 QTL 研究中候选位置的重要新资源。此外，我们还利用基因型、基因表达性状和表型性状之间的相关结构分析来进一步表征顺式作用控制下的肝病表达基因，并强调在分离群体中整合遗传学和基因表达数据的优点和缺点。
We previously reported the analysis of genome-wide expression profiles and various diabetes-related traits in a segregating cross between inbred mouse strains C57BL/6J (B6) and DBA/2J (DBA). By considering transcript levels as quantitative traits, we identified several thousand expression quantitative trait loci [eQTL] with LOD score > 4.3. We now experimentally address the problem of multiple comparisons by estimating the fraction of false-positive eQTL that are Under cis-acting regulation. For this, we have Utilized a classic cis-trans test with (B6 x DBA)F-1 rilice to determine the relative levels of transcripts from the B6 and DBA alleles. The results suggest that at least 64% of cis-acting eQTL with LOD > 4.3 are true Positives, while the remaining, 36% could not be confirmed as truly cis-acting. Moreover, we find that > 96% of apparent cis-acting eQTL occur ill regions that do not share SNP haplotypes. Cis-acting eQTL serve as ail important new resource for the identification of positional candidates ill QTL studies ill mice. Also, we Use the analysis of the correlation structures between genotypes, gene expression traits, and phenotypic traits to further characterize genes expressed ill liver that are Under cis-acting control, and highlight the advantages and disadvantages of integrating genetics and gene expression data in segregating populations.