Epigenetic inheritance in plants

The function of plant genomes depends on chromatin marks such as the methylation of DNA and the post-translational modification of histones. Techniques for studying model plants such as Arabidopsis thaliana have enabled researchers to begin to uncover the pathways that establish and maintain chromatin modifications, and genomic studies are allowing the mapping of modifications such as DNA methylation on a genome-wide scale. Small RNAs seem to be important in determining the distribution of chromatin modifications, and RNA might also underlie the complex epigenetic interactions that occur between homologous sequences. Plants use these epigenetic silencing mechanisms extensively to control development and parent-of-origin imprinted gene expression.     

Insights into hominid evolution from the gorilla genome sequence

Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution.     

Melanoma genome sequencing reveals frequent PREX2 mutations

Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life. To obtain a comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome), intermediate in those originating from hair-bearing skin of the trunk (5-55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)--a PTEN-interacting protein and negative regulator of PTEN in breast cancer--as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma.     

Who reports address changes through the healthcare system? The characteristics of laggers and non-reporters using the Northern Ireland Longitudinal Study

Address information from health service professionals is already important for the delivery of health care and population monitoring and screening. It is also important for statistical purposes such as the estimation of migration and small area populations and its importance could increase as the decade progresses and alternatives are sought to the traditional census. Because of this, it is important to understand more about the accuracy of address information provided through the health care system.This article considers the characteristics of 'laggers' - those who delay in reporting address changes - and 'non-reporters' - those who on occasion fail to report their addresses.The article finds that, as might be expected, laggers and non-reporters tend to be male and resident in urban and deprived areas. However, less expectedly, older people tend to be laggers, as are owner occupiers, those who are not ill, those who have some educational qualifications, and those who are self-employed. Some non-reporters are also more likely to be employed in professional jobs and to be unmarried (for example single, remarried and divorced). This suggests that poor address information is not just a problem associated with the socially deprived and the young but also with some more affluent groups such as those not experiencing limiting long-term illness. The article concludes by arguing that the checking of patients' address information should be collected under the Quality and Outcomes Framework (QOF) as a performance indicator.