Genetic dissection of the Mom5 modifier locus and evaluation of Mom5 candidate genes

Karla L. Otterpohl, Karen A Gould

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Germline mutations in the adenomatous polyposis coli (APC) gene cause familial adenomatous polyposis (FAP), a hereditary colon cancer syndrome in which affected individuals may develop 100–1000s of colonic adenomas. In families affected by FAP, adenoma number can vary markedly between individuals, despite the fact that these individuals carry the same APC mutation. In at least some FAP pedigrees, evidence suggests that these phenotypic differences are caused by segregating modifier alleles that impact adenoma number. However, identifying these modifiers in the human population is difficult, therefore mouse models are essential. Using the ApcMin/+ mouse colon cancer model, we previously mapped one such modifier, Mom5, to a 25 Mbp region of chromosome 5 that contains hundreds of genes. The purpose of the present study was to refine the Mom5 interval and evaluate candidate genes for the Mom5 modifier of intestinal neoplasia. Recombinant mice were used to narrow the Mom5 interval to 8.1 Mbp containing 70 genes. In silico and gene expression analyses were utilized to identify and evaluate potential candidate genes that reside within this interval. These analyses identified seven genes within the Mom5 interval that contain variants between the B6 and 129P2 strains. These genes represent the most likely candidates for the Mom5 modifier.

Original languageEnglish (US)
Pages (from-to)235-247
Number of pages13
JournalMammalian Genome
Volume26
Issue number5-6
DOIs
StatePublished - Jun 2 2015

Fingerprint

Adenomatous Polyposis Coli
Dissection
Adenoma
Genes
Colonic Neoplasms
Hereditary Neoplastic Syndromes
Modifier Genes
APC Genes
Chromosomes, Human, Pair 5
Germ-Line Mutation
Pedigree
Computer Simulation
Alleles
Gene Expression
Mutation
Population
Neoplasms

ASJC Scopus subject areas

  • Genetics

Cite this

Genetic dissection of the Mom5 modifier locus and evaluation of Mom5 candidate genes. / Otterpohl, Karla L.; Gould, Karen A.

In: Mammalian Genome, Vol. 26, No. 5-6, 02.06.2015, p. 235-247.

Research output: Contribution to journalArticle

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