Genetics, Vol. 159, 371-387, September 2001, Copyright © 2001

A Statistical Framework for Quantitative Trait Mapping

Saunak Sena and Gary A. Churchilla
a The Jackson Laboratory, Bar Harbor, Maine 04609

Corresponding author: Gary A. Churchill, The Jackson Laboratory, 600 Main St., Bar Harbor, ME 04609., garyc{at}jax.org (E-mail)

Communicating editor: S. TAVARÉ

We describe a general statistical framework for the genetic analysis of quantitative trait data in inbred line crosses. Our main result is based on the observation that, by conditioning on the unobserved QTL genotypes, the problem can be split into two statistically independent and manageable parts. The first part involves only the relationship between the QTL and the phenotype. The second part involves only the location of the QTL in the genome. We developed a simple Monte Carlo algorithm to implement Bayesian QTL analysis. This algorithm simulates multiple versions of complete genotype information on a genomewide grid of locations using information in the marker genotype data. Weights are assigned to the simulated genotypes to capture information in the phenotype data. The weighted complete genotypes are used to approximate quantities needed for statistical inference of QTL locations and effect sizes. One advantage of this approach is that only the weights are recomputed as the analyst considers different candidate models. This device allows the analyst to focus on modeling and model comparisons. The proposed framework can accommodate multiple interacting QTL, nonnormal and multivariate phenotypes, covariates, missing genotype data, and genotyping errors in any type of inbred line cross. A software tool implementing this procedure is available. We demonstrate our approach to QTL analysis using data from a mouse backcross population that is segregating multiple interacting QTL associated with salt-induced hypertension.




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Combining Data From Multiple Inbred Line Crosses Improves the Power and Resolution of Quantitative Trait Loci Mapping
Genetics, March 1, 2005; 169(3): 1699 - 1709.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. M. Dorward, K. L. Shultz, L. G. Horton, R. Li, G. A. Churchill, and W. G. Beamer
Distal Chr 4 Harbors a Genetic Locus (Gct1) Fundamental for Spontaneous Ovarian Granulosa Cell Tumorigenesis in a Mouse Model
Cancer Res., February 15, 2005; 65(4): 1259 - 1264.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
M. L. Guler, D. L. Ligons, Y. Wang, M. Bianco, K. W. Broman, and N. R. Rose
Two Autoimmune Diabetes Loci Influencing T Cell Apoptosis Control Susceptibility to Experimental Autoimmune Myocarditis
J. Immunol., February 15, 2005; 174(4): 2167 - 2173.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
A. E. Baum, L. C. Solberg, P. Kopp, N. Ahmadiyeh, G. Churchill, J. S. Takahashi, J. L. Jameson, and E. E. Redei
Quantitative Trait Loci Associated with Elevated Thyroid-Stimulating Hormone in the Wistar-Kyoto Rat
Endocrinology, February 1, 2005; 146(2): 870 - 878.
[Abstract] [Full Text] [PDF]

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 GeneticsHome page
T. Niu, A. A. Ding, R. Kreutz, and K. Lindpaintner
An Expectation-Maximization-Likelihood-Ratio Test for Handling Missing Data: Application in Experimental Crosses
Genetics, February 1, 2005; 169(2): 1021 - 1031.
[Abstract] [Full Text] [PDF]

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 GeneticsHome page
M. J. Sillanpaa and M. Bhattacharjee
Bayesian Association-Based Fine Mapping in Small Chromosomal Segments
Genetics, January 1, 2005; 169(1): 427 - 439.
[Abstract] [Full Text] [PDF]

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 GeneticsHome page
G. Diao, D. Y. Lin, and F. Zou
Mapping Quantitative Trait Loci With Censored Observations
Genetics, November 1, 2004; 168(3): 1689 - 1698.
[Abstract] [Full Text] [PDF]

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 J. Lipid Res.Home page
N. Ishimori, R. Li, P. M. Kelmenson, R. Korstanje, K. A. Walsh, G. A. Churchill, K. Forsman-Semb, and B. Paigen
Quantitative trait loci that determine plasma lipids and obesity in C57BL/6J and 129S1/SvImJ inbred mice
J. Lipid Res., September 1, 2004; 45(9): 1624 - 1632.
[Abstract] [Full Text] [PDF]

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 GeneticsHome page
M. Bogdan, J. K. Ghosh, and R. W. Doerge
Modifying the Schwarz Bayesian Information Criterion to Locate Multiple Interacting Quantitative Trait Loci
Genetics, June 1, 2004; 167(2): 989 - 999.
[Abstract] [Full Text] [PDF]

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 J. Lipid Res.Home page
R. Korstanje, R. Li, T. Howard, P. Kelmenson, J. Marshall, B. Paigen, and G. Churchill
Influence of sex and diet on quantitative trait loci for HDL cholesterol levels in an SM/J by NZB/BlNJ intercross population
J. Lipid Res., May 1, 2004; 45(5): 881 - 888.
[Abstract] [Full Text] [PDF]

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 BloodHome page
L. L. Peters, R. A. Swearingen, S. G. Andersen, B. Gwynn, A. J. Lambert, R. Li, S. E. Lux, and G. A. Churchill
Identification of quantitative trait loci that modify the severity of hereditary spherocytosis in wan, a new mouse model of band-3 deficiency
Blood, April 15, 2004; 103(8): 3233 - 3240.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
M. A. Lyons, R. Korstanje, R. Li, K. A. Walsh, G. A. Churchill, M. C. Carey, and B. Paigen
Genetic contributors to lipoprotein cholesterol levels in an intercross of 129S1/SvImJ and RIIIS/J inbred mice
Physiol Genomics, April 13, 2004; 17(2): 114 - 121.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
K. DiPetrillo, S.-W. Tsaih, S. Sheehan, C. Johns, P. Kelmenson, H. Gavras, G. A. Churchill, and B. Paigen
Genetic analysis of blood pressure in C3H/HeJ and SWR/J mice
Physiol Genomics, April 13, 2004; 17(2): 215 - 220.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
M. A. Lyons, H. Wittenburg, R. Li, K. A. Walsh, R. Korstanje, G. A. Churchill, M. C. Carey, and B. Paigen
Quantitative trait loci that determine lipoprotein cholesterol levels in an intercross of 129S1/SvImJ and CAST/Ei inbred mice
Physiol Genomics, March 12, 2004; 17(1): 60 - 68.
[Abstract] [Full Text] [PDF]

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 Arterioscler. Thromb. Vasc. Bio.Home page
R. Korstanje, J. J. Albers, G. Wolfbauer, R. Li, A.-Y. Tu, G. A. Churchill, and B. J. Paigen
Quantitative Trait Locus Mapping of Genes That Regulate Phospholipid Transfer Activity in SM/J and NZB/BlNJ Inbred Mice
Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 155 - 160.
[Abstract] [Full Text] [PDF]

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 Arterioscler. Thromb. Vasc. Bio.Home page
N. Ishimori, R. Li, P. M. Kelmenson, R. Korstanje, K. A. Walsh, G. A. Churchill, K. Forsman-Semb, and B. Paigen
Quantitative Trait Loci Analysis for Plasma HDL-Cholesterol Concentrations and Atherosclerosis Susceptibility Between Inbred Mouse Strains C57BL/6J and 129S1/SvImJ
Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 161 - 166.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
M. W. McBride, F. J. Charchar, D. Graham, W. H. Miller, P. Strahorn, F. J. Carr, and A. F. Dominiczak
Functional genomics in rodent models of hypertension
J. Physiol., January 1, 2004; 554(1): 56 - 63.
[Abstract] [Full Text] [PDF]

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 GeneticsHome page
K. L. Montooth, J. H. Marden, and A. G. Clark
Mapping Determinants of Variation in Energy Metabolism, Respiration and Flight in Drosophila
Genetics, October 1, 2003; 165(2): 623 - 635.
[Abstract] [Full Text] [PDF]

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 GeneticsHome page
N. Yi, S. Xu, and D. B. Allison
Bayesian Model Choice and Search Strategies for Mapping Interacting Quantitative Trait Loci
Genetics, October 1, 2003; 165(2): 867 - 883.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
M. Sedelis, K. Hofele, R. K. W. Schwarting, J. P. Huston, and J. K. Belknap
Chromosomal Loci Influencing the Susceptibility to the Parkinsonian Neurotoxin 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine
J. Neurosci., September 10, 2003; 23(23): 8247 - 8253.
[Abstract] [Full Text] [PDF]

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 J. Lipid Res.Home page
M. A. Lyons, H. Wittenburg, R. Li, K. A. Walsh, M. R. Leonard, R. Korstanje, G. A. Churchill, M. C. Carey, and B. Paigen
Lith6: a new QTL for cholesterol gallstones from an intercross of CAST/Ei and DBA/2J inbred mouse strains
J. Lipid Res., September 1, 2003; 44(9): 1763 - 1771.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
M. A. Lyons, H. Wittenburg, R. Li, K. A. Walsh, M. R. Leonard, G. A. Churchill, M. C. Carey, and B. Paigen
New quantitative trait loci that contribute to cholesterol gallstone formation detected in an intercross of CAST/Ei and 129S1/SvImJ inbred mice
Physiol Genomics, August 15, 2003; 14(3): 225 - 239.
[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
R. R. Hoopes Jr., R. Reid, S. Sen, C. Szpirer, P. Dixon, A. A.J. Pannett, R. V. Thakker, D. A. Bushinsky, and S. J. Scheinman
Quantitative Trait Loci for Hypercalciuria in a Rat Model of Kidney Stone Disease
J. Am. Soc. Nephrol., July 1, 2003; 14(7): 1844 - 1850.
[Abstract] [Full Text] [PDF]

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 GeneticsHome page
N. Yi, V. George, and D. B. Allison
Stochastic Search Variable Selection for Identifying Multiple Quantitative Trait Loci
Genetics, July 1, 2003; 164(3): 1129 - 1138.
[Abstract] [Full Text] [PDF]

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 Genome ResHome page
X. Wang, I. Le Roy, E. Nicodeme, R. Li, R. Wagner, C. Petros, G. A. Churchill, S. Harris, A. Darvasi, J. Kirilovsky, et al.
Using Advanced Intercross Lines for High-Resolution Mapping of HDL Cholesterol Quantitative Trait Loci
Genome Res., July 1, 2003; 13(7): 1654 - 1664.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
M. A. Lyons, H. Wittenburg, R. Li, K. A. Walsh, G. A. Churchill, M. C. Carey, and B. Paigen
Quantitative trait loci that determine lipoprotein cholesterol levels in DBA/2J and CAST/Ei inbred mice,
J. Lipid Res., May 1, 2003; 44(5): 953 - 967.
[Abstract] [Full Text] [PDF]