Genome Scans for Transmission Ratio Distortion Regions in Mice

Author:

Casellas Joaquim12,Gularte Rodrigo J2,Farber Charles R23,Varona Luis4,Mehrabian Margarete5,Schadt Eric E6,Lusis Aldon J5,Attie Alan D7,Yandell Brian S8,Medrano Juan F2

Affiliation:

1. Departament de Ciència Animal i dels Aliments, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain

2. Department of Animal Science, University of California, Davis, California 95616-8521

3. Departments of Medicine, Biochemistry and Molecular Genetics and Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia 22908

4. Departamento de Anatomía, Embriología y Genética Animal, Universidad de Zaragoza, 50013 Zaragoza, Spain

5. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095-1679

6. Rosetta Inpharmatics, Seattle, Washington 98109

7. Department of Biochemistry

8. Departments of Statistics and Horticulture, University of Wisconsin, Madison, Wisconsin 53706

Abstract

Abstract Transmission ratio distortion (TRD) is the departure from the expected genotypic frequencies under Mendelian inheritance. This departure can be due to multiple physiological mechanisms during gametogenesis, fertilization, fetal and embryonic development, and early neonatal life. Although a few TRD loci have been reported in mouse, inheritance patterns have never been evaluated for TRD. In this article, we developed a Bayesian binomial model accounting for additive and dominant deviation TRD mechanisms. Moreover, this model was used to perform genome-wide scans for TRD quantitative trait loci (QTL) on six F2 mouse crosses involving between 296 and 541 mice and between 72 and 1854 genetic markers. Statistical significance of each model was checked at each genetic marker with Bayes factors. Genome scans revealed overdominance TRD QTL located in mouse chromosomes 1, 2, 12, 13, and 14 and additive TRD QTL in mouse chromosomes 2, 3, and 15, although these results did not replicate across mouse crosses. This research contributes new statistical tools for the analysis of specific genetic patterns involved in TRD in F2 populations, our results suggesting a relevant incidence of TRD phenomena in mouse with important implications for both statistical analyses and biological research.

Publisher

Oxford University Press (OUP)

Subject

Genetics

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