Cis -acting expression quantitative trait loci in mice
Open accessAbstract
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 × DBA)F 1 mice 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 in regions that do not share SNP haplotypes. Cis -acting eQTL serve as an important new resource for the identification of positional candidates in QTL studies in mice. Also, we use the analysis of the correlation structures between genotypes, gene expression traits, and phenotypic traits to further characterize genes expressed in liver that are under cis -acting control, and highlight the advantages and disadvantages of integrating genetics and gene expression data in segregating populations.
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Large datasets of eQTLs are now available for a number of tissues in humans and animal models.
“Large datasets of eQTLs are now available for a number of tissues in humans and animal models [17, 22, 25, 26].”
From Multi-omics approaches to disease (2017) · cites this paper as [26]
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References 26 · Cited by 273
- Authors
- Doss, S., Schadt, E. E., Drake, T. A., & Lusis, A. J.
- Affiliations
- University of California, Los Angeles (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- Lusis, Aldons J.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-04-18
- Volume
- 15
- Issue
- 5
- Pages
- 681-691
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC1088296
- OpenAlex
- W2041959263
- Cited by
- 273
- References
- 26
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 20 · 2020: 3 · 2019: 8 · 2018: 3 · 2017: 13 · 2016: 7 · 2015: 6 · 2014: 11 · 2013: 8 · 2012: 14
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HL‐28481, HL30568)
- National Heart, Lung, and Blood Institute (HL3 0568, HL28481, P01HL030568, P01HL028481)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Keywords
- false positive rate, multiple comparisons, mRNA levels, SNP haplotypes, hepatic gene expression, positional candidate genes
- MeSH terms
- Alleles, Animals, Chromosome Mapping, Gene Expression Regulation, Genetic Complementation Test, Haplotypes, Liver, Lod Score, Mice, Inbred C57BL, Mice, Inbred DBA, Phenotype, Genome, Computational Biology, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Mice
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