Confirmation of maternal transmission ratio distortion at Om and direct evidence that the maternal and paternal “DDK syndrome” genes are linked

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Abstract
The polar, preimplantation-embryo lethal phenotype known as the“DDK syndrome” in the mouse is the result of the complex interaction of genetic factors and a parental-origin effect. We previously observed a modest degree of transmission-ratio distortion in favor of the inheritance of DDK alleles in the Ovum mutant (Om) region of Chromosome (Chr) 11, among offspring of reciprocal F1-hybrid females and C57BL/6 males. In this study, we confirm that a significant excess of offspring inherit DDK alleles from F1 mothers and demonstrate that the preference for the inheritance of DDK alleles is not a specific bias against the C57BL/6 allele or a simple preference for offspring that are heterozygous at Om. Because none of the previous genetic models for the inheritance of the“DDK syndrome” predicted transmission-ratio distortion through F1 females, we reconsidered the possibility that the genes encoding the maternal and paternal components of this phenotype were not linked. We have examined the fertility phenotype of N2 females and demonstrate that the inter-strain fertility of these females is correlated with their genotype in the Om region. This result establishes, directly, that the genes encoding the maternal and paternal components of the DDK syndrome are genetically linked.