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Originally published as Genetics Published Articles Ahead of Print on September 19, 2005.

Genetics, Vol. 172, 411-423, January 2006, Copyright © 2006
doi:10.1534/genetics.105.047118

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The Paternal Gene of the DDK Syndrome Maps to the Schlafen Gene Cluster on Mouse Chromosome 11

Timothy A. Bell*,1, Elena de la Casa-Esperón{dagger},1, Heather E. Doherty*,{ddagger},1, Folami Ideraabdullah*,{ddagger},1, Kuikwon Kim*,{ddagger}, Yunfei Wang*, Leslie A. Lange*,§, Kirk Wilhemsen*,{ddagger},§,**,{dagger}{dagger}, Ethan M. Lange*,§,§§, Carmen Sapienza{dagger},*** and Fernando Pardo-Manuel de Villena*,{ddagger},§,**,2

* Department of Genetics, {ddagger} Curriculum in Genetics and Molecular Biology, § Carolina Center for Genome Sciences, ** Lineberger Comprehensive Cancer Center, {dagger}{dagger} Department of Neurology and §§ Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina 27599-7264, {dagger} Fels Institute for Cancer Research and Molecular Biology and *** Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140

2 Corresponding author: Department of Genetics, Campus Box 7264, 103 Mason Farm Road, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7264.
E-mail: fernando{at}med.unc.edu

The DDK syndrome is an early embryonic lethal phenotype observed in crosses between females of the DDK inbred mouse strain and many non-DDK males. Lethality results from an incompatibility between a maternal DDK factor and a non-DDK paternal gene, both of which have been mapped to the Ovum mutant (Om) locus on mouse chromosome 11. Here we define a 465-kb candidate interval for the paternal gene by recombinant progeny testing. To further refine the candidate interval we determined whether males from 17 classical and wild-derived inbred strains are interfertile with DDK females. We conclude that the incompatible paternal allele arose in the Mus musculus domesticus lineage and that incompatible strains should share a common haplotype spanning the paternal gene. We tested for association between paternal allele compatibility/incompatibility and 167 genetic variants located in the candidate interval. Two diallelic SNPs, located in the Schlafen gene cluster, are completely predictive of the polar-lethal phenotype. These SNPs also predict the compatible or incompatible status of males of five additional strains.




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F. Y. Ideraabdullah, K. Kim, D. Pomp, J. L. Moran, D. Beier, and F. P.-M. d. Villena
Rescue of the Mouse DDK Syndrome by Parent-of-Origin-Dependent Modifiers
Biol Reprod, February 1, 2007; 76(2): 286 - 293.
[Abstract] [Full Text] [PDF]


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Copyright © 2006 by the Genetics Society of America.