論文 - 詳細
| RRC ID | 2787 |
|---|---|
| 著者 | Petretto E, Mangion J, Dickens NJ, Cook SA, Kumaran MK, Lu H, Fischer J, Maatz H, Kren V, Pravenec M, Hubner N, Aitman TJ. |
| タイトル | Heritability and tissue specificity of expression quantitative trait loci. |
| ジャーナル | PLoS Genet |
| Abstract |
Variation in gene expression is heritable and has been mapped to the genome in humans and model organisms as expression quantitative trait loci (eQTLs). We applied integrated genome-wide expression profiling and linkage analysis to the regulation of gene expression in fat, kidney, adrenal, and heart tissues using the BXH/HXB panel of rat recombinant inbred strains. Here, we report the influence of heritability and allelic effect of the quantitative trait locus on detection of cis- and trans-acting eQTLs and discuss how these factors operate in a tissue-specific context. We identified several hundred major eQTLs in each tissue and found that cis-acting eQTLs are highly heritable and easier to detect than trans-eQTLs. The proportion of heritable expression traits was similar in all tissues; however, heritability alone was not a reliable predictor of whether an eQTL will be detected. We empirically show how the use of heritability as a filter reduces the ability to discover trans-eQTLs, particularly for eQTLs with small effects. Only 3% of cis- and trans-eQTLs exhibited large allelic effects, explaining more than 40% of the phenotypic variance, suggestive of a highly polygenic control of gene expression. Power calculations indicated that, across tissues, minor differences in genetic effects are expected to have a significant impact on detection of trans-eQTLs. Trans-eQTLs generally show smaller effects than cis-eQTLs and have a higher false discovery rate, particularly in more heterogeneous tissues, suggesting that small biological variability, likely relating to tissue composition, may influence detection of trans-eQTLs in this system. We delineate the effects of genetic architecture on variation in gene expression and show the sensitivity of this experimental design to tissue sampling variability in large-scale eQTL studies. |
| 巻・号 | 2(10) |
| ページ | e172 |
| 公開日 | 2006-10-20 |
| DOI | 10.1371/journal.pgen.0020172 |
| PII | 06-PLGE-RA-0248R2 |
| PMID | 17054398 |
| PMC | PMC1617131 |
| MeSH | Alleles Animals Gene Expression Regulation / genetics* Genetic Variation Genome / genetics Male Organ Specificity* Quantitative Trait Loci / genetics* Quantitative Trait, Heritable* RNA, Messenger / genetics RNA, Messenger / metabolism Rats Rats, Inbred Strains |
| IF | 5.175 |
| 引用数 | 151 |
| WOS 分野 | GENETICS & HEREDITY |
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