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

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^,1, Heather E. Doherty^*,,1, Folami Ideraabdullah^*,,1, Kuikwon Kim^*,, Yunfei Wang^*, Leslie A. Lange^*,, Kirk Wilhemsen^*,,,**,, Ethan M. Lange^*,,, Carmen Sapienza^,*** and Fernando Pardo-Manuel de Villena^*,,,**,2

^* Department of Genetics, Curriculum in Genetics and Molecular Biology, Carolina Center for Genome Sciences, ^** Lineberger Comprehensive Cancer Center, Department of Neurology and Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina 27599-7264, 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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