This Article Full Text Full Text (PDF) Supplemental Research Data All Versions of this Article: gr.3216905v1 15/5/681    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Doss, S. Articles by Lusis, A. J. Search for Related Content PubMed PubMed Citation Articles by Doss, S. Articles by Lusis, A. J. Social Bookmarking                   What's this?

Letter

Cis-acting expression quantitative trait loci in mice

¹ Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA ² Department of Microbiology, Immunology, & Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA ³ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA ⁴ Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA ⁵ Molecular Biology Institute, UCLA, Los Angeles, California 90095, USA ⁶ Rosetta Inpharmatics, A wholly owned subsidiary of Merck & Co., Inc., Kirkland, Washington 98034, USA

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)F₁ 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.

Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.3216905. Article published online ahead of print in April 2005.

⁷ Corresponding author.
E-mail jlusis{at}mednet.ucla.edu; fax (310) 794-7345.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Benovoy, T. Kwan, and J. Majewski Effect of polymorphisms within probe-target sequences on olignonucleotide microarray experiments Nucleic Acids Res., August 1, 2008; 36(13): 4417 - 4423. [Abstract] [Full Text] [PDF]

				M. Mackiewicz, B. Paigen, N. Naidoo, and A. I. Pack Analysis of the QTL for sleep homeostasis in mice: Homer1a is a likely candidate Physiol Genomics, March 10, 2008; 33(1): 91 - 99. [Abstract] [Full Text] [PDF]

				B. Liu, A. de la Fuente, and I. Hoeschele Gene Network Inference via Structural Equation Modeling in Genetical Genomics Experiments Genetics, March 1, 2008; 178(3): 1763 - 1776. [Abstract] [Full Text] [PDF]

				A. Genissel, L. M. McIntyre, M. L. Wayne, and S. V. Nuzhdin Cis and Trans Regulatory Effects Contribute to Natural Variation in Transcriptome of Drosophila melanogaster Mol. Biol. Evol., January 1, 2008; 25(1): 101 - 110. [Abstract] [Full Text] [PDF]

				R. B.H. Williams, E. K.F. Chan, M. J. Cowley, and P. F.R. Little The influence of genetic variation on gene expression Genome Res., December 1, 2007; 17(12): 1707 - 1716. [Abstract] [Full Text] [PDF]

				E. M. Sellner, J. W. Kim, M. C. McClure, K. H. Taylor, R. D. Schnabel, and J. F. Taylor BOARD-INVITED REVIEW: Applications of genomic information in livestock J Anim Sci, December 1, 2007; 85(12): 3148 - 3158. [Abstract] [Full Text] [PDF]

				K. Ganguly, T. Stoeger, S. C. Wesselkamper, C. Reinhard, M. A. Sartor, M. Medvedovic, C. R. Tomlinson, I. Bolle, J. M. Mason, G. D. Leikauf, et al. Candidate genes controlling pulmonary function in mice: transcript profiling and predicted protein structure Physiol Genomics, November 14, 2007; 31(3): 410 - 421. [Abstract] [Full Text] [PDF]

				R. Rottscheidt and B. Harr Extensive Additivity of Gene Expression Differentiates Subspecies of the House Mouse Genetics, November 1, 2007; 177(3): 1553 - 1567. [Abstract] [Full Text] [PDF]

				S. Chiu, K. Kim, K. A. Haus, G. M. Espinal, L. V. Millon, and C. H. Warden Identification of positional candidate genes for body weight and adiposity in subcongenic mice Physiol Genomics, September 11, 2007; 31(1): 75 - 85. [Abstract] [Full Text] [PDF]

				S. S. Wang, E. E. Schadt, H. Wang, X. Wang, L. Ingram-Drake, W. Shi, T. A. Drake, and A. J. Lusis Identification of Pathways for Atherosclerosis in Mice: Integration of Quantitative Trait Locus Analysis and Global Gene Expression Data Circ. Res., August 3, 2007; 101(3): e11 - e30. [Abstract] [Full Text] [PDF]

				D. Chalothorn, J. A. Clayton, H. Zhang, D. Pomp, and J. E. Faber Collateral density, remodeling, and VEGF-A expression differ widely between mouse strains Physiol Genomics, July 18, 2007; 30(2): 179 - 191. [Abstract] [Full Text] [PDF]

				D. L. Crawford and M. F. Oleksiak The biological importance of measuring individual variation J. Exp. Biol., May 1, 2007; 210(9): 1613 - 1621. [Abstract] [Full Text] [PDF]

				H. Meng, I. Vera, N. Che, X. Wang, S. S. Wang, L. Ingram-Drake, E. E. Schadt, T. A. Drake, and A. J. Lusis Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics PNAS, March 13, 2007; 104(11): 4530 - 4535. [Abstract] [Full Text] [PDF]

				N. M. Springer and R. M. Stupar Allelic variation and heterosis in maize: How do two halves make more than a whole? Genome Res., March 1, 2007; 17(3): 264 - 275. [Abstract] [Full Text] [PDF]

				A. F. McRae, N. A. Matigian, L. Vadlamudi, J. C. Mulley, B. Mowry, N. G. Martin, S. F. Berkovic, N. K. Hayward, and P. M. Visscher Replicated effects of sex and genotype on gene expression in human lymphoblastoid cell lines Hum. Mol. Genet., February 15, 2007; 16(4): 364 - 373. [Abstract] [Full Text] [PDF]

				B. E. Stranger, M. S. Forrest, M. Dunning, C. E. Ingle, C. Beazley, N. Thorne, R. Redon, C. P. Bird, A. de Grassi, C. Lee, et al. Relative Impact of Nucleotide and Copy Number Variation on Gene Expression Phenotypes Science, February 9, 2007; 315(5813): 848 - 853. [Abstract] [Full Text] [PDF]

				E. E. Schadt and P. Y. Lum Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Reverse engineering gene networks to identify key drivers of complex disease phenotypes J. Lipid Res., December 1, 2006; 47(12): 2601 - 2613. [Abstract] [Full Text] [PDF]

				S.-I. Lee, D. Pe'er, A. M. Dudley, G. M. Church, and D. Koller Identifying regulatory mechanisms using individual variation reveals key role for chromatin modification PNAS, September 19, 2006; 103(38): 14062 - 14067. [Abstract] [Full Text] [PDF]

				R. Kiekens, A. Vercauteren, B. Moerkerke, E. Goetghebeur, H. Van Den Daele, R. Sterken, M. Kuiper, F. van Eeuwijk, and M. Vuylsteke Genome-wide screening for cis-regulatory variation using a classical diallel crossing scheme Nucleic Acids Res., August 2, 2006; 34(13): 3677 - 3686. [Abstract] [Full Text] [PDF]

				R. M. Stupar and N. M. Springer Cis-transcriptional Variation in Maize Inbred Lines B73 and Mo17 Leads to Additive Expression Patterns in the F1 Hybrid Genetics, August 1, 2006; 173(4): 2199 - 2210. [Abstract] [Full Text] [PDF]

				P. D. Lee, B. Ge, C. M. T. Greenwood, D. Sinnett, Y. Fortin, S. Brunet, A. Fortin, M. Takane, E. Skamene, T. Pastinen, et al. Mapping cis-acting regulatory variation in recombinant congenic strains Physiol Genomics, April 13, 2006; 25(2): 294 - 302. [Abstract] [Full Text] [PDF]

				P.V. K. Pant, H. Tao, E. J. Beilharz, D. G. Ballinger, D. R. Cox, and K. A. Frazer Analysis of allelic differential expression in human white blood cells Genome Res., March 1, 2006; 16(3): 331 - 339. [Abstract] [Full Text] [PDF]

				H. Li, H. Chen, L. Bao, K. F. Manly, E. J. Chesler, L. Lu, J. Wang, M. Zhou, R. W. Williams, and Y. Cui Integrative genetic analysis of transcription modules: towards filling the gap between genetic loci and inherited traits Hum. Mol. Genet., February 1, 2006; 15(3): 481 - 492. [Abstract] [Full Text] [PDF]

				L. Flaherty, B. Herron, and D. Symula Genomics of the future: Identification of quantitative trait loci in the mouse Genome Res., December 1, 2005; 15(12): 1741 - 1745. [Abstract] [Full Text] [PDF]

				R. Alberts, P. Terpstra, L. V. Bystrykh, G. de Haan, and R. C. Jansen A Statistical Multiprobe Model for Analyzing cis and trans Genes in Genetical Genomics Experiments With Short-Oligonucleotide Arrays Genetics, November 1, 2005; 171(3): 1437 - 1439. [Abstract] [Full Text] [PDF]