CONFIRMATION OF MATERNAL TRANSMISSION RATIO DISTORTION AT OM AND DIRECT EVIDENCE THAT THE MATERNAL AND PATERNAL DDK SYNDROME GENES ARE LINKED

The polar, preimplantation-embryo lethal phenotype known as the ''DDK syndrome'' in the mouse is the result of the complex interaction of ge netic factors and a parental-origin effect. We previously observed a m odest degree of transmission-ratio distortion in favor of the inherita nce of DDK alleles in the Ovum mutant (Om) region of Chromosome (Chr) 11, among offspring of reciprocal F-1-hybrid females and C57BL/6 males . In this study, we confirm that a significant excess of offspring inh erit DDK alleles from F-1 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 heterozyg ous at Om. Because none of the previous genetic models for the inherit ance of the ''DDK syndrome'' predicted transmission-ratio distortion t hrough F-1 females, we reconsidered the possibility that the genes enc oding the maternal and paternal components of this phenotype were not linked. We have examined the fertility phenotype of N-2 females and de monstrate that the inter-strain fertility of these females is correlat ed with their genotype in the Om region. This result establishes, dire ctly, that the genes encoding the maternal and paternal components of the DDK syndrome are genetically linked.