Genetic architecture and sexual conflict in the life history of Drosophila

Because males and females of a species express many homologous traits, sex-specific selection on these traits can shift the opposite sex away from its phenotypic optimum. This mode of sexually antagonistic selection, known as intralocus sexual conflict (IaSC), arises when the evolution of sexual dimorphism is constrained by the two sexes sharing a common gene pool. As IaSC has been historically overlooked, many outstanding questions remain. For example, what is its contribution in maintaining genetic variation for fitness in populations? What characters underlie this variation in fitness? How does the selection history of the population influence the standing genetic variation? I used the model organism Drosophila melanogaster to attempt to resolve some of these questions. The first part of my Master’s project involved assessing the detectability of sexually antagonistic alleles in populations at different stages of adaptation to the laboratory. For the second part of my Master’s project, I looked for evidence of conflict during the development of body size, a well-known sexually dimorphic trait. While the first part of my thesis proved inconclusive, the second part revealed a surprising source of sexual conflict in pre-adult stages of D. melanogaster.

Genetic Polymorphisms in Replication-related Genes and Risk of Breast Cancer Among European and East Asian Women

Background: The role of common, low to intermediate risk alleles in breast cancer need to be examined due to their relatively high prevalence. Among many cellular pathways, replication has a pivotal role in cell division and frequently targeted during carcinogenesis. Replication is governed by a host of genes involved in a number of different pathways. This study investigates the effects of replication-gene variants in relation to breast cancer and how this relationship is affected by ethnicity, menopausal status and breast tumour subtype. Methods: Data from a case-control study with 997 incident breast cancer cases and 1,050 age frequency matched controls in Vancouver, British Columbia and Kingston, Ontario were used. Unconditional logistic regression was used to calculate odds ratios between 45 replication gene variants and breast cancer risk, assuming an additive genetic model adjusted for age and centre, presented for Europeans and East Asians separately. Polytomous logistic regression was used to assess odds ratios between each SNP and four breast cancer subtypes defined by hormone receptor status among Europeans. All analyses were stratified by menopausal status. The Benjamini–Hochberg false discovery rate (FDR) was used to address multiple comparisons. Results: Among Europeans, the SNPs in FGFR2, TOX3 and 11q13 loci were associated with breast cancer after controlling for multiple comparisons. Test of heterogeneity showed the SNPs rs1045185, rs4973768, rs672888, rs1219648, rs2420946 among Europeans and rs889312 among East Asians conferred differential risk across the tumour subtypes. Conclusions: Specific SNPs in replication genes were associated with breast cancer, and the risk level differed by tumour subtype defined by ER/PR/Her2 status and ethnicity.