Genetics, Vol. 151, 785-795, February 1999, Copyright © 1999

Multiple-Trait Quantitative Trait Loci Analysis Using a Large Mouse Sibship

Anne U. Jacksona, Alison Fornésa, Andrzej Galeckic,d, Richard A. Millerb,c,d, and David T. Burkea,d
a Department of Human Genetics, Ann Arbor, Michigan 48109
b Department of Pathology, Ann Arbor, Michigan 48109
c Ann Arbor Department of Veteran's Affairs Medical Center, Ann Arbor, Michigan 48109
d Institute of Gerontology, University of Michigan, Ann Arbor, Michigan 48109

Corresponding author: David T. Burke, Department of Human Genetics, University of Michigan Medical School, 1150 West Medical Center Dr., Ann Arbor, MI 48109-0618., dtburke{at}umich.edu (E-mail)

Communicating editor: T. F. C. MACKAY

Quantitative trait loci influencing several phenotypes were assessed using a genetically heterogeneous mouse population. The 145 individuals were produced by a cross between (BALB/cJ x C57BL/6J)F1 females and (C3H/HeJ x DBA/2J)F1 males. The population is genetically equivalent to full siblings derived from heterozygous parents, with known linkage phase. Each individual in the population represents a unique combination of alleles from the inbred grandparents. Quantitative phenotypes for eight T cell measures were obtained at 8 and 18 mo of age. Single-marker locus, repeated measures analysis of variance identified nine marker-phenotype associations with an experimentwise significance level of P < 0.05. Six of the eight quantitative phenotypes could be associated with at least one locus having experiment-wide significance. Composite interval, repeated measures analysis of variance identified 13 chromosomal regions with comparisonwise (nominal) significance associations of P < 0.001. The heterozygous-parent cross provides a reproducible, general method for identification of loci associated with quantitative trait phenotypes or repeated phenotypic measures.




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