Transmission of X-linked Ovarian Cancer: Characterization and Implications

We recently reported evidence that a strong, BRCA-independent locus on the X-chromosome may contribute to ovarian cancer predisposition in families ascertained from the Familial Ovarian Cancer Registry (Buffalo, NY, USA). While it has been estimated that approximately 20% of all ovarian cancer cases are hereditary, it is possible that a significant proportion of cases previously believed to be sporadic may, in fact, be X-linked. Such X-linked disease has a distinct pattern; it implies that a father will necessarily pass a risk allele to each of his daughters, increasing the prevalence of cancers clustered within a family. X-chromosome inactivation further influences the expression of X-linked alleles and may represent a novel target for screening and therapy. Herein, we review the current literature regarding X-linked ovarian cancer and interpret allele transmission-based models to characterize X-linked ovarian cancer and develop a framework for clinical and epidemiological familial ascertainment to inform the design of future studies.

The ebb and flow of heteroplasmy during intra-species hybridization in Caenorhabditis briggsae

ABSTRACTMitochondria are typically maternally inherited. In many species, this transmission pattern is produced by sperm-borne mitochondria being eliminated either from sperm before fertilization or from the embryo after fertilization. In the nematode Caenorhabditis briggsae, repeatedly backcrossing hybrids to genetically diverse males can elicit paternal mitochondrial transmission. Studies of other taxa also suggest that hybridization increases paternal mitochondrial transmission. Thus, hybrid genotypes might disrupt the systems that normally prevent paternal mitochondrial transmission. Given the reliance of a number of genetic analyses on the assumption of purely maternal mitochondrial inheritance, it would be broadly valuable to learn more about the processes embryos employ to prevent sperm-borne mitochondria from persisting in offspring, as well as the circumstances under which paternal transmission might be expected to occur. To quantify the tempo of paternal mitochondrial transmission in hybrids, we assessed the presence of paternal mitotypes in replicate lines at three timepoints spanning fifteen generations. All lines exhibited paternal mitochondrial transmission. However, this heteroplasmy always then resolved to homoplasmy for the maternal mitotype. Additionally, one nuclear locus exhibited allele transmission ratio distortion that might reflect mito-nuclear co-evolution. This study frames the genetic architecture of a hybrid genetic incompatibility that leads to paternal mitochondrial transmission and to a reduction in hybrid fitness.

Power approximation of the transmission disequilibrium test

In this paper we apply Poisson distribution in order to approximate the power of the Transmission Disequilibrium Test (TDT). In this research we calculated the power of the TDT for different values of sample size n and different values of allele transmission frequencies p. The research showed that Poisson approximation have smaller errors than Normal approximation when the power is between 0.8 and 0.95 and sample size m is equal or bigger than 50.