Nature Reviews Genetics最新文献

Traditionally, differences among individuals have been divided into genetic and environmental causes. However, both types of variation can underlie regulatory changes in gene expression — that is, epigenetic changes — that persist across cell divisions (developmental differentiation) and even across generations (transgenerational inheritance). Increasingly, epigenetic variation among individuals is recognized as an important factor in human diseases and ageing. Moreover, non-genetic inheritance can lead to evolutionary changes within populations that differ from those expected by genetic inheritance alone. Despite its importance, causally linking epigenetic variation to phenotypic differences across individuals has proven difficult, particularly when epigenetic variation operates independently of genetic variation. New genomic approaches are providing unprecedented opportunity to measure and perturb epigenetic variation, helping to elucidate the role of epigenetic variation in mediating the genotype–phenotype map. Here, we review studies that have advanced our understanding of how epigenetic variation contributes to phenotypic differences between individuals within and across generations, and provide a unifying framework that allows historical and mechanistic perspectives to more fully inform one another.

Comparative genomics, whereby the genomes of different species are compared, has the potential to address broad and fundamental questions at the intersection of genetics and evolution. However, species, genomes and genes cannot be considered as independent data points within statistical tests. Closely related species tend to be similar because they share genes by common descent, which must be accounted for in analyses. This problem of non-independence may be exacerbated when examining genomes or genes but can be addressed by applying phylogeny-based methods to comparative genomic analyses. Here, we review how controlling for phylogeny can change the conclusions of comparative genomics studies. We address common questions on how to apply these methods and illustrate how they can be used to test causal hypotheses. The combination of rapidly expanding genomic datasets and phylogenetic comparative methods is set to revolutionize the biological insights possible from comparative genomic studies.

Loss of Y chromosome (LOY) is the most commonly occurring post-zygotic (somatic) mutation in male individuals. The past decade of research suggests that LOY has important effects in shaping the activity of the immune system, and multiple studies have shown the effects of LOY on a range of diseases, including cancer, neurodegeneration, cardiovascular disease and acute infection. Epidemiological findings have been corroborated by functional analyses providing insights into the mechanisms by which LOY modulates the immune system; in particular, a causal role for LOY in cardiac fibrosis, bladder cancer and Alzheimer disease has been indicated. These insights show that LOY is a highly dynamic mutation (such that LOY clones expand and contract with time) and has pleiotropic, cell-type-specific effects. Here, we review the status of the field and highlight the potential of LOY as a biomarker and target of new therapeutics that aim to counteract its negative effects on the immune system.

Cancer incidence and mortality rates can vary widely among different racial and ethnic groups, attributed to a complex interplay of genetic, environmental and social factors. Recently, substantial progress has been made in investigating hereditary genetic risk factors and in characterizing tumour genomes. However, most research has been conducted in individuals of European ancestries and, increasingly, in individuals of Asian ancestries. The study of germline and somatic genetics in cancer across racial and ethnic groups using omics technologies offers opportunities to identify similarities and differences in both heritable traits and the molecular features of cancer genomes. An improved understanding of population-specific cancer genomics, as well as translation of those findings across populations, will help reduce cancer disparities and ensure that personalized medicine and public health approaches are equitable across racial and ethnic groups.