High levels of gene flow and genetic diversity in Irish populations of Salix caprea L. inferred from chloroplast and nuclear SSR markers

peer-reviewedBackground Salix caprea is a cold-tolerant pioneer species that is ecologically important in Europe and western and central Asia. However, little data is available on its population genetic structure and molecular ecology. We describe the levels of geographic population genetic structure in natural Irish populations of S. caprea and determine the extent of gene flow and sexual reproduction using both chloroplast and nuclear simple sequence repeats (SSRs). Results A total of 183 individuals from 21 semi-natural woodlands were collected and genotyped. Gene diversity across populations was high for the chloroplast SSRs (H T  = 0.21-0.58) and 79 different haplotypes were discovered, among them 48% were unique to a single individual. Genetic differentiation of populations was found to be between moderate and high (mean G ST  = 0.38). For the nuclear SSRs, G ST was low at 0.07 and observed heterozygosity across populations was high (H O  = 0.32-0.51); only 9.8% of the genotypes discovered were present in two or more individuals. For both types of markers, AMOVA showed that most of the variation was within populations. Minor geographic pattern was confirmed by a Bayesian clustering analysis. Gene flow via pollen was found to be approximately 7 times more important than via seeds. Conclusions The data are consistent with outbreeding and indicate that there are no significant barriers for gene flow within Ireland over large geographic distances. Both pollen-mediated and seed-mediated gene flow were found to be high, with some of the populations being more than 200 km apart from each other. These findings could simply be due to human intervention through seed trade or accidental transportation of both seeds and pollen. These results are of value to breeders wishing to exploit natural genetic variation and foresters having to choose planting material.Teagasc Walsh Fellowship Programm

Cryptic introgression into the kidney saxifrage (Saxifraga hirsuta) from its more abundant sympatric congener Saxifraga spathularis, and the potential risk of genetic assimilation

Background and Aims Although hybridization can play a positive role in plant evolution, it has been shown that excessive unidirectional hybridization can result in replacement of a species’ gene pool, and even the extinction of rare species via genetic assimilation. This study examines levels of introgression between the common Saxifraga spathularis and its rarer congener S. hirsuta, which have been observed to hybridize in the wild where they occur sympatrically. Methods Seven species-specific single nucleotide polymorphisms (SNPs) were analysed in 1025 plants representing both species and their hybrid, S. × polita, from 29 sites across their ranges in Ireland. In addition, species distribution modelling was carried out to determine whether the relative abundance of the two parental species is likely to change under future climate scenarios. Key Results Saxifraga spathularis individuals tended to be genetically pure, exhibiting little or no introgression from S. hirsuta, but significant levels of introgression of S. spathularis alleles into S. hirsuta were observed, indicating that populations exhibiting S. hirsuta morphology are more like a hybrid swarm, consisting of backcrosses and F(2)s. Populations of the hybrid, S. × polita, were generally comprised of F(1)s or F(2)s, with some evidence of backcrossing. Species distribution modelling under projected future climate scenarios indicated an increase in suitable habitats for both parental species. Conclusions Levels of introgression observed in this study in both S. spathularis and S. hirsuta would appear to be correlated with the relative abundance of the species. Significant introgression of S. spathularis alleles was detected in the majority of the S. hirsuta populations analysed and, consequently, ongoing introgression would appear to represent a threat to the genetic integrity of S. hirsuta, particularly in areas where the species exists sympatrically with its congener and where it is greatly outnumbered

Marginal/peripheral populations of forest tree species and their conservation status: report for Atlantic region

This report is a synthesis of information from the national reports, prepared as part of the COST Action FP1202 Strengthening conservation: a key issue for adaptation of marginal/peripheral populations of forest trees to climate change in Europe (MaPFGR). The individual national reports can be found as part of the supplemental data to the COST action. The data compiled in this report indicate that the Atlantic area has sufficient resources in terms of knowledge and capacity to assess the potential impact of climate change on marginal and peripheral (MaP) sites within the area. Maps of vegetation, soil, climate and climatic predictions are publicly available for most countries and often are of high quality and resolution. These can be utilized to help identify MaP sites and populations in the Atlantic area. In addition, some species have been characterized genetically and the genetic data can also be utilized to identify and characterize sites. However, genetic data is not universally available and in particular may be absent for peripheral sites. There are many data sources for phenotypic traits, such as data from provenance trials but these have not been assessed for MaP populations. There may not be sufficient legislative capacity for the conservation of MaP populations in comparison to, for example, annex habitats of the EU Habitats Directive. Although some of the MaP sites lie within Natura 2000 boundaries, many are not in protected areas. If MaP populations are not characterized and conserved there is a risk of losing traits that may be of potential in adaptation to climate change. A detailed spatial analysis incorporating all of the data is needed to give a comprehensive assessment of the potential threats to MaP populations in this area

Dairy Ingredients for Chocolate and Confectionery Products.

End of Project ReportHigh free-fat, spray-dried powders were successfully produced at a lower fat content (40% rather than 56%) using ultrafiltration. Chocolates made from these powders had improved flow properties and superior quality. The stability, viscosity and firmness of toffees were improved by optimising the casein, whey protein and lactose levels of skim milk powders used in their manufacture.Department of Agriculture, Food and the Marin

Evolution-based approach needed for the conservation and silviculture of peripheral forest tree populations

The fate of peripheral forest tree populations is of particular interest in the context of climate change. These populations may concurrently be those where the most significant evolutionary changes will occur; those most facing increasing extinction risk; the source of migrants for the colonization of new areas at leading edges; or the source of genetic novelty for reinforcing standing genetic variation in various parts of the range. Deciding which strategy to implement for conserving and sustainably using the genetic resources of peripheral forest tree populations is a challenge. Here, we review the genetic and ecological processes acting on different types of peripheral populations and indicate why these processes may be of general interest for adapting forests and forest management to climate change. We particularly focus on peripheral populations at the rear edge of species distributions where environmental challenges are or will become most acute. We argue that peripheral forest tree populations are “natural laboratories” for resolving priority research questions such as how the complex interaction between demographic processes and natural selection shape local adaptation; and whether genetic adaptation will be sufficient to allow the long-term persistence of species within their current distribution. Peripheral populations are key assets for adaptive forestry which need specific measures for their preservation. The traditionally opposing views which may exist between conservation planning and sustainable forestry need to be reconciled and harmonized for managing peripheral populations. Based on existing knowledge, we suggest approaches and principles which may be used for the management and conservation of these distinctive and valuable populations, to maintain active genetic and ecological processes that have sustained them over time

An inherited duplication at the gene p21 protein-activated Kinase 7 (PAK7) is a risk factor for psychosis

FUNDING Funding for this study was provided by the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z), the Wellcome Trust (072894/Z/03/Z, 090532/Z/09/Z and 075491/Z/04/B), NIMH grants (MH 41953 and MH083094) and Science Foundation Ireland (08/IN.1/B1916). We acknowledge use of the Trinity Biobank sample from the Irish Blood Transfusion Service; the Trinity Centre for High Performance Computing; British 1958 Birth Cohort DNA collection funded by the Medical Research Council (G0000934) and the Wellcome Trust (068545/Z/02) and of the UK National Blood Service controls funded by the Wellcome Trust. Chris Spencer is supported by a Wellcome Trust Career Development Fellowship (097364/Z/11/Z). Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust. ACKNOWLEDGEMENTS The authors sincerely thank all patients who contributed to this study and all staff who facilitated their involvement. We thank W. Bodmer and B. Winney for use of the People of the British Isles DNA collection, which was funded by the Wellcome Trust. We thank Akira Sawa and Koko Ishzuki for advice on the PAK7–DISC1 interaction experiment and Jan Korbel for discussions on mechanism of structural variation.Peer reviewedPublisher PD

Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch

Silver birch (Betula pendula) is a pioneer boreal tree that can be induced to flower within 1 year. Its rapid life cycle, small (440-Mb) genome, and advanced germplasm resources make birch an attractive model for forest biotechnology. We assembled and chromosomally anchored the nuclear genome of an inbred B. pendula individual. Gene duplicates from the paleohexaploid event were enriched for transcriptional regulation, whereas tandem duplicates were overrepresented by environmental responses. Population resequencing of 80 individuals showed effective population size crashes at major points of climatic upheaval. Selective sweeps were enriched among polyploid duplicates encoding key developmental and physiological triggering functions, suggesting that local adaptation has tuned the timing of and cross-talk between fundamental plant processes. Variation around the tightly-linked light response genes PHYC and FRS10 correlated with latitude and longitude and temperature, and with precipitation for PHYC. Similar associations characterized the growth-promoting cytokinin response regulator ARR1, and the wood development genes KAK and MED5A.Peer reviewe

Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Barrett’s Esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia. Barrett’s Esophagus strongly predisposes to esophageal adenocarcinoma (EAC), a tumour with a very poor prognosis. We have undertaken the first genome-wide association study on Barrett’s Esophagus, comprising 1,852 UK cases and 5,172 UK controls in discovery and 5,986 cases and 12,825 controls in the replication. Two regions were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10−9, OR(95%CI) =1.21(1.13-1.28)) and chromosome 16q24, rs9936833 (Pcombined=2.74×10−10, OR(95%CI) =1.14(1.10-1.19)). The top SNP on chromosome 6p21 is within the major histocompatibility complex, and the closest protein-coding gene to rs9936833 on chromosome 16q24 is FOXF1, which is implicated in esophageal development and structure. We found evidence that the genetic component of Barrett’s Esophagus is mediated by many common variants of small effect and that SNP alleles predisposing to obesity also increase risk for Barrett’s Esophagus

Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes.

Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.JW is supported by a Cancer Research UK Cambridge Cancer Centre Clinical Research Training Fellowship. Funding for the NIHR BioResource – Rare diseases project was provided by the National Institute for Health Research (NIHR, grant number RG65966). ERM acknowledges support from the European Research Council (Advanced Researcher Award), NIHR (Senior Investigator Award and Cambridge NIHR Biomedical Research Centre), Cancer Research UK Cambridge Cancer Centre and Medical Research Council Infrastructure Award. The University of Cambridge has received salary support in respect of EM from the NHS in the East of England through the Clinical Academic Reserve. The views expressed are those of the authors and not necessarily those of the NHS or Department of Health. DGE is an NIHR Senior Investigator and is supported by the all Manchester NIHR Biomedical Research Centre

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre