The paternal gene of the DDK syndrome maps to the Schlafen gene cluster on mouse chromosome 11.
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.
Bell
Timothy A
TA
Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
de la Casa-Esperón
Elena
E
Doherty
Heather E
HE
Ideraabdullah
Folami
F
Kim
Kuikwon
K
Wang
Yunfei
Y
Lange
Leslie A
LA
Wilhemsen
Kirk
K
Lange
Ethan M
EM
Sapienza
Carmen
C
de Villena
Fernando Pardo-Manuel
FP
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics*; D003433:Crosses, Genetic; D005260:Female; D005298:Fertility / Q000235:genetics*; D005804:Genes, Lethal; D008040:Genetic Linkage; D018392:Genomic Imprinting / Q000502:physiology*; D006239:Haplotypes / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D005810:Multigene Family; D010641:Phenotype; D010802:Phylogeny; D013577:Syndrome
D018797:Cell Cycle Proteins; C504818:schlafen-1 protein, mouse