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The maintenance of genetic diversity across generations depends on both the number of reproducing males and females. Variance in reproductive success, multiple paternity and litter size can all affect the relative contributions of male and female parents to genetic variation of progeny. The mating system of the wild boar (Sus scrofa) has been described as polygynous, although evidence of multiple paternity in litters has been found. Using 14 microsatellite markers, we evaluated the contribution of males and females to genetic variation in the next generation in independent wild boar populations from the Iberian Peninsula and Hungary. Genetic contributions of males and females were obtained by distinguishing the paternal and maternal genetic component inherited by the progeny. We found that the paternally inherited genetic component of progeny was more diverse than the maternally inherited component. Simulations showed that this finding might be due to a sampling bias. However, after controlling for the bias by fitting both the genetic diversity in the adult population and the number of reproductive individuals in the models, paternally inherited genotypes remained more diverse than those inherited maternally. Our results suggest new insights into how promiscuous mating systems can help maintain genetic variation.

DNA damage and replication checkpoints mediated by the ATR-CHEK1 pathway are key to the maintenance of genome stability, and both ATR and CHEK1 have been proposed as potential breast cancer susceptibility genes. Many novel variants recently identified by the large resequencing projects have not yet been thoroughly tested in genome-wide association studies for breast cancer susceptibility. We therefore used a tagging SNP (tagSNP) approach based on recent SNP data available from the 1000 genomes projects, to investigate the roles of ATR and CHEK1 in breast cancer risk and survival. ATR and CHEK1 tagSNPs were genotyped in the Sheffield Breast Cancer Study (SBCS; 1011 cases and 1024 controls) using Illumina GoldenGate assays. Untyped SNPs were imputed using IMPUTE2, and associations between genotype and breast cancer risk and survival were evaluated using logistic and Cox proportional hazard regression models respectively on a per allele basis. Significant associations were further examined in a meta-analysis of published data or confirmed in the Utah Breast Cancer Study (UBCS). The most significant associations for breast cancer risk in SBCS came from rs6805118 in ATR (p=7.6 x 10(-5)) and rs2155388 in CHEK1 (p=3.1 x 10(-6)), but neither remained significant after meta-analysis with other studies. However, meta-analysis of published data revealed a weak association between the ATR SNP rs1802904 (minor allele frequency is 12%) and breast cancer risk, with a summary odds ratio (confidence interval) of 0.90 (0.83-0.98) [p=0.0185] for the minor allele. Further replication of this SNP in larger studies is warranted since it is located in the target region of 2 microRNAs. No evidence of any survival effects of ATR or CHEK1 SNPs were identified. We conclude that common alleles of ATR and CHEK1 are not implicated in breast cancer risk or survival, but we cannot exclude effects of rare alleles and of common alleles with very small effect sizes.

Heterozygote advantage, or overdominance, remains a popular and persuasive explanation for the maintenance of genetic variation in natural populations in the face of selection. However, despite being first proposed more than 80 years ago, there remain few examples that fit the criteria for heterozygote advantage, all of which are associated with disease resistance and are maintained only in the presence of disease or other gene-by-environment interaction. Here we report five new examples of heterozygote advantage, based around polymorphisms in the BMP15 and GDF9 genes that affect female fecundity in domesticated sheep and are not reliant on disease for their maintenance. Five separate mutations in these members of the transforming growth factor beta (TGFbeta) superfamily give phenotypes with fitness differentials characteristic of heterozygous advantage. In each case, one copy of the mutant allele increases ovulation rate, and ultimately litter size per ewe lambing, relative to the wildtype. However, homozygous ewes inheriting mutant alleles from both parents have impaired oocyte development and maturation, which results in small undeveloped ovaries and infertility. Using data collected over many years on ovulation rates, litter size, and lambing rates, we have calculated the equilibrium solution for each of these polymorphisms using standard population genetic theory. The predicted equilibrium frequencies obtained for these mutant alleles range from 0.11 to 0.23, which are amongst the highest yet reported for a polymorphism maintained by heterozygote advantage. These are amongst the most frequent and compelling examples of heterozygote advantage yet described and the first documented examples of heterozygote advantage that are not reliant on a disease interaction for their maintenance.