title: Genetic evaluation of candidate genes for the Mom1 modifier of intestinal neoplasia in mice.
abstract: As genetic mapping of quantitative trait loci (QTL) becomes routine, the challenge is to identify the underlying genes. This paper develops rigorous genetic tests for evaluation of candidate genes for a QTL, involving determination of allelic status in inbred strains and fine-structure genetic mapping. For the Mom1 modifier of intestinal adenomas caused by ApcMin, these tests are used to evaluate two candidate genes: Pla2g2a, a secretory phospholipase, and Rap1GAP, a GTPase activating protein. Rap1GAP passes the first test but is excluded by a single fine-structure recombinant. Pla2g2a passes both tests and is a strong candidate for Mom1. Significantly, we also find that ApcMin-induced adenomas remain heterozygous for the Mom1 region, consistent with Mom1 acting outside the tumor lineage and encoding a secreted product.
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Gould
authors.forename: C
authors.initials: C
authors.lastname: Luongo
authors.forename: A R
authors.initials: AR
authors.lastname: Moser
authors.forename: M K
authors.initials: MK
authors.lastname: McNeley
authors.forename: N
authors.initials: N
authors.lastname: Borenstein
authors.forename: A
authors.initials: A
authors.lastname: Shedlovsky
authors.forename: W F
authors.initials: WF
authors.lastname: Dove
authors.forename: K
authors.initials: K
authors.lastname: Hong
authors.forename: W F
authors.initials: WF
authors.lastname: Dietrich
authors.forename: E S
authors.initials: ES
authors.lastname: Lander
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D017491:Genes, APC; D007414:Intestinal Neoplasms / Q000235:genetics*; D051379:Mice