| 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
|
| リソース情報 |
| ラット |
|
