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

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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 Apc Min/+ 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.

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Acknowledgments

The University of Nebraska Microarray Core receives partial support from the NCRR (5P20RR016469, RR018788-08) and the National Institute for General Medical Science (NIGMS) (8P20GM103427, P20GM103471). This publication’s contents are the sole responsibility of the authors and do not necessarily represent the official views of the NIH or NIGMS. We wish to also thank Kristi Anderson for her help with the SNP genotyping assays and Dr. Alicia Cleveland Scott for sequencing the Nos3 coding sequence from 129P2 and B6 strains.

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  1. Department of Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, 985805 Nebraska Medical Center, Omaha, NE, 68198-5805, USA

    Karla L. Otterpohl & Karen A. Gould

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  1. Karla L. Otterpohl
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  2. Karen A. Gould
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Correspondence to Karen A. Gould.

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Otterpohl, K.L., Gould, K.A. Genetic dissection of the Mom5 modifier locus and evaluation of Mom5 candidate genes. Mamm Genome 26, 235–247 (2015). https://doi.org/10.1007/s00335-015-9567-x

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