Convergent evolutionary processes driven by foraging opportunity in two sympatric morph pairs of Arctic charr with contrasting post-glacial origins

The expression of two or more discrete phenotypes amongst individuals within a species (morphs) provides multiple modes upon which selection can act semi-independently, and thus may be an important stage in speciation. In the present study, we compared two sympatric morph systems aiming to address hypotheses related to their evolutionary origin. Arctic charr in sympatry in Loch Tay, Scotland, exhibit one of two discrete, alternative body size phenotypes at maturity (large or small body size). Arctic charr in Loch Awe segregate into two temporally segregated spawning groups (breeding in either spring or autumn). Mitochondrial DNA restriction fragment length polymorphism analysis showed that the morph pairs in both lakes comprise separate gene pools, although segregation of the Loch Awe morphs is more subtle than that of Loch Tay. We conclude that the Loch Awe morphs diverged in situ (within the lake), whereas Loch Tay morphs most likely arose through multiple invasions by different ancestral groups that segregated before post-glacial invasion (i.e. in allopatry). Both morph pairs showed clear trophic segregation between planktonic and benthic resources (measured by stable isotope analysis) but this was significantly less distinct in Loch Tay than in Loch Awe. By contrast, both inter-morph morphological and life-history differences were more subtle in Loch Awe than in Loch Tay. The strong ecological but relatively weak morphological and life-history divergence of the in situ derived morphs compared to morphs with allopatric origins indicates a strong link between early ecological and subsequent genetic divergence of sympatric origin emerging species pairs. The emergence of parallel specialisms despite distinct genetic origins of these morph pairs suggests that the effect of available foraging opportunities may be at least as important as genetic origin in structuring sympatric divergence in post-glacial fishes with high levels of phenotypic plasticity. (c) 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, , .

Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms

A genomewide linkage scan was carried out in eight clinical samples of informative schizophrenia families. After all quality control checks, the analysis of 707 European-ancestry families included 1615 affected and 1602 unaffected genotyped individuals, and the analysis of all 807 families included 1900 affected and 1839 unaffected individuals. Multipoint linkage analysis with correction for marker-marker linkage disequilibrium was carried out with 5861 single nucleotide polymorphisms (SNPs; Illumina version 4.0 linkage map). Suggestive evidence for linkage ( European families) was observed on chromosomes 8p21, 8q24.1, 9q34 and 12q24.1 in nonparametric and/or parametric analyses. In a logistic regression allele-sharing analysis of linkage allowing for intersite heterogeneity, genomewide significant evidence for linkage was observed on chromosome 10p12. Significant heterogeneity was also observed on chromosome 22q11.1. Evidence for linkage across family sets and analyses was most consistent on chromosome 8p21, with a one-LOD support interval that does not include the candidate gene NRG1, suggesting that one or more other susceptibility loci might exist in the region. In this era of genomewide association and deep resequencing studies, consensus linkage regions deserve continued attention, given that linkage signals can be produced by many types of genomic variation, including any combination of multiple common or rare SNPs or copy number variants in a region. Molecular Psychiatry (2009) 14, 786-795; doi:10.1038/mp.2009.11; published online 17 February 2009

No consistent evidence for association between mtDNA variants and Alzheimer disease

Although several studies have described an association between Alzheimer disease (AD) and genetic variation of mitochondrial DNA (mtDNA), each has implicated different mtDNA variants, so the role of mtDNA in the etiology of AD remains uncertain.

Extensive local-scale gene flow and long-term population stability in the intertidal mollusc Katharina tunicata (Mollusca: Polyplacophora)

The dispersal capabilities of intertidal organisms may represent a key factor to their survival in the face of global warming, as species that cannot adapt to the various effects of climate change will have to migrate to track suitable habitat. Although species with pelagic larval phases might be expected to have a greater capacity for dispersal than those with benthic larvae, interspecies comparisons have shown that this is not always the case. Consequently, population genetic approaches are being increasingly used to gain insights into dispersal through studying patterns of gene flow. In the present study, we used nuclear single-nucleotide polymorphisms (SNPs) and mitochondrial DNA (mtDNA) sequencing to elucidate fine-scale patterns of genetic variation between populations of the Black Katy Chiton, Katharina tunicata, separated by 15-150 km in south-west Vancouver Island. Both the nuclear and mitochondrial data sets revealed no genetic differentiation between the populations studied, and an isolation-with-migration analysis indicated extensive local-scale gene flow, suggesting an absence of barriers to dispersal. Population demographic analysis also revealed long-term population stability through previous periods of climate change associated with the Pleistocene glaciations. Together, the findings of the present study suggest that this high potential for dispersal may allow K. tunicata to respond to current global warming by tracking suitable habitat, consistent with its long-term demographic stability through previous changes in the Earth's climate. (C) 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 106, 589597.

Haplotype association analysis of genes within the WNT signalling pathways in diabetic nephropathy

Background: Renal interstitial fibrosis and glomerular sclerosis are hallmarks of diabetic nephropathy (DN) and several studies have implicated members of the WNT pathways in these pathological processes. This study comprehensively examined common genetic variation within the WNT pathway for association with DN.

Methods: Genes within the WNT pathways were selected on the basis of nominal significance and consistent direction of effect in the GENIE meta-analysis dataset. Common SNPs and common haplotypes were examined within the selected WNT pathway genes in a white population with type 1 diabetes, discordant for DN (cases: n = 718; controls: n = 749). SNPs were genotyped using Sequenom or Taqman assays. Association analyses were performed using PLINK, to compare allele and haplotype frequencies in cases and controls. Correction for multiple testing was performed by either permutation testing or using false discovery rate.

Results: A logistic regression model including collection centre, duration of diabetes, and average HbA1c as covariates highlighted three SNPs in GSK3B (rs17810235, rs17471, rs334543), two in DAAM1 (rs1253192, rs1252906) and one in NFAT5 (rs17297207) as being significantly (P< 0.05) associated with DN, however these SNPs did not remain significant after correction for multiple testing. Logistic regression of haplotypes, with ESRD as the outcome, and pairwise interaction analyses did not yield any significant results after correction for multiple testing.

Conclusions: These results indicate that both common SNPs and common haplotypes of WNT pathway genes are not strongly associated with DN. However, this does not completely exclude these or the WNT pathways from association with DN, as unidentified rare genetic or copy number variants could still contribute towards the genetic architecture of DN.© 2013 Kavanagh et al.; licensee BioMed Central Ltd.

On Irish stickleback:Morphological diversification in a secondary contact zone

Question: How parallel is adaptive evolution when it occurs from different genetic backgrounds? Background: Divergent evolutionary lineages of several post-glacial fish species including the threespine stickleback are found together in Ireland. Goals: To investigate the morphological diversity of stickleback populations in Ireland and assess whether morphology evolved in parallel between evolutionary lineages. Methods: We sampled stickleback from lake, river, and coastal habitats across Ireland. Microsatellite and mitochondrial DNA data revealed evolutionary history. Geometric morphometrics and linear trait measurements characterized morphology. We used a multivariate approach to quantify parallel and non-parallel divergence within and between lineages. Results: Repeated evolution of similar morphologies in similar habitats occurred across Ireland, concordant with patterns observed elsewhere in the stickleback distribution. A strong pattern of habitat-specific morphology existed even among divergent lineages. Furthermore, a strong signal of shared morphological divergence occurred along a marine-freshwater axis. Evidently, deterministic natural selection played a more important role in driving freshwater adaptation than independent evolutionary history. © 2013 Mark Ravinet.

CNV analysis in a large schizophrenia sample implicates deletions at 16p12.1 and SLC1A1 and duplications at 1p36.33 and CGNL1

Large and rare copy number variants (CNVs) at several loci have been shown to increase risk for schizophrenia. Aiming to discover novel susceptibility CNV loci, we analysed 6,882 cases and 11,255 controls genotyped on Illumina arrays, most of which have not been used for this purpose before. We identified genes enriched for rare exonic CNVs among cases, and then attempted to replicate the findings in an additional 14,568 cases and 15,274 controls. In a combined analysis of all samples, 12 distinct loci were enriched among cases with nominal levels of significance (P500kb), rare CNVs showed a 1.2% excess in cases after excluding known schizophrenia-associated loci, suggesting that additional susceptibility loci exist. However, even larger samples are required for their discovery.

Evidence that duplications of 22q11.2 protect against schizophrenia

A number of large, rare copy number variants (CNVs) are deleterious for neurodevelopmental disorders, but large, rare, protective CNVs have not been reported for such phenotypes. Here we show in a CNV analysis of 47?005 individuals, the largest CNV analysis of schizophrenia to date, that large duplications (1.5-3.0?Mb) at 22q11.2-the reciprocal of the well-known, risk-inducing deletion of this locus-are substantially less common in schizophrenia cases than in the general population (0.014% vs 0.085%, OR=0.17, P=0.00086). 22q11.2 duplications represent the first putative protective mutation for schizophrenia.

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

Identifying rare, highly penetrant risk mutations may be an important step in dissecting the molecular etiology of schizophrenia. We conducted a gene-based analysis of large (>100kb), rare copy number variants (CNVs) in the Wellcome Trust Case Control Consortium 2 (WTCCC2) schizophrenia sample of 1,564 cases and 1,748 controls all from Ireland, and further extended the analysis to include an additional 5,196 UK controls. We found association with duplications at chr20p12.2 (P=0.007) and evidence of replication in large independent European schizophrenia (P=0.052) and UK bipolar disorder case-control cohorts (P=0.047). A combined analysis of Irish/UK subjects including additional psychosis cases (schizophrenia and bipolar disorder) identified 22 carriers in 11,707 cases and 10 carriers in 21,204 controls (meta-analysis CMH P value=2x10(-4) (odds ratio (OR)=11.3, 95% CI=3.7, ∞)). Nineteen of the 22 cases and 8 of the 10 controls carried duplications starting at 9.68Mb with similar breakpoints across samples. By haplotype analysis and sequencing we identified a tandem ∼149kb duplication overlapping the gene p21 Protein-Activated Kinase 7 (PAK7, also called PAK5) which was in linkage disequilibrium with local haplotypes (P=2.5x10(-21)), indicative of a single ancestral duplication event. We confirmed the breakpoints in 8/8 carriers tested and found co-segregation of the duplication with illness in two additional family members of one of the affected probands. We demonstrate that PAK7 is developmentally co-expressed with another known psychosis risk gene (DISC1) suggesting a potential molecular mechanism involving aberrant synapse development and plasticity.

Genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis

Tuberculosis (TB) caused by Mycobacterium bovis is a re-emerging disease of livestock that is of major economic importance worldwide, as well as being a zoonotic risk there is significant heritability for host resistance to bovine TB (bTB) in dairy cattle. To identify resistance loci for bTB, we undertook a genome-wide association study in female Holstein-Friesian cattle with 592 cases and 559 age-matched controls from case herds. Cases and controls were categorised into distinct phenotypes: skin test and lesion positive vs skin test negative on multiple occasions, respectively these animals were genotyped with the Illumina BovineHD 700K BeadChip. Genome-wide rapid association using linear and logistic mixed models and regression (GRAMMAR), regional heritability mapping (RHM) and haplotype-sharing analysis identified two novel resistance loci that attained chromosome-wise significance, protein tyrosine phosphatase receptor T (PTPRT; P=4.8 × 10 -7) and myosin IIIB (MYO3B; P=5.4 × 10 -6). We estimated that 21% of the phenotypic variance in TB resistance could be explained by all of the informative single-nucleotide polymorphisms, of which the region encompassing the PTPRT gene accounted for 6.2% of the variance and a further 3.6% was associated with a putative copy number variant in MYO3B the results from this study add to our understanding of variation in host control of infection and suggest that genetic marker-based selection for resistance to bTB has the potential to make a significant contribution to bTB control.

Genetic polymorphisms and kidney transplant outcomes

Purpose of review: Gene polymorphism studies are growing at a quasiexponential rate and aim to improve immediate and long-term outcomes in renal transplantation. This review highlights recent evidence and potential future directions for genetic research studies.

Recent findings: Studies are largely based on immunity, inflammation and pharmacogenetics, investigating mostly 'surrogate' outcomes with sometimes conflicting results. However, the last 12 months has also heralded the emergence of important genome-wide association studies on transplantation, more robust replicated multicentre analyses of candidate gene variants, meta-analyses, and an increasing interest in copy number variation and donor genetics.

Summary: These studies set the scene for further investigation, aiming to understand pathways of disease and biomarkers of risk, and are leading to a greater understanding of the biology of transplantation. Future studies will require focus on donor : recipient and gene : environment interactions, and an integrated approach of 'transplantomics' to evaluate long-term outcomes in multinational collaborations.

On Irish sticklebacks: morphological diversification in a secondary contact zone

Question: How parallel is adaptive evolution when it occurs from different genetic backgrounds?
Background: Divergent evolutionary lineages of several post-glacial fish species including the threespine stickleback are found together in Ireland.
Goals: To investigate the morphological diversity of stickleback populations in Ireland and assess whether morphology evolved in parallel between evolutionary lineages.
Methods: We sampled stickleback from lake, river, and coastal habitats across Ireland. Microsatellite and mitochondrial DNA data revealed evolutionary history. Geometric morphometrics and linear trait measurements characterized morphology. We used a multivariate approach to quantify parallel and non-parallel divergence within and between lineages.
Results: Repeated evolution of similar morphologies in similar habitats occurred across Ireland, concordant with patterns observed elsewhere in the stickleback distribution. A strong pattern of habitat-specific morphology existed even among divergent lineages. Furthermore, a strong signal of shared morphological divergence occurred along a marine–freshwater axis. Evidently, deterministic natural selection played a more important role in driving freshwater adaptation than independent evolutionary history.

A primer for use of genetic tools in selecting and testing the suitability of set-aside sites protected from deep-sea seafloor massive sulfide mining activities

Seafloor massive sulfide (SMS) mining will likely occur at hydrothermal systems in the near future. Alongside their mineral wealth, SMS deposits also have considerable biological value. Active SMS deposits host endemic hydrothermal vent communities, whilst inactive deposits support communities of deep water corals and other suspension feeders. Mining activities are expected to remove all large organisms and suitable habitat in the immediate area, making vent endemic organisms particularly at risk from habitat loss and localised extinction. As part of environmental management strategies designed to mitigate the effects of mining, areas of seabed need to be protected to preserve biodiversity that is lost at the mine site and to preserve communities that support connectivity among populations of vent animals in the surrounding region. These "set-aside" areas need to be biologically similar to the mine site and be suitably connected, mostly by transport of larvae, to neighbouring sites to ensure exchange of genetic material among remaining populations. Establishing suitable set-asides can be a formidable task for environmental managers, however the application of genetic approaches can aid set-aside identification, suitability assessment and monitoring. There are many genetic tools available, including analysis of mitochondrial DNA (mtDNA) sequences (e.g. COI or other suitable mtDNA genes) and appropriate nuclear DNA markers (e.g. microsatellites, single nucleotide polymorphisms), environmental DNA (eDNA) techniques and microbial metagenomics. When used in concert with traditional biological survey techniques, these tools can help to identify species, assess the genetic connectivity among populations and assess the diversity of communities. How these techniques can be applied to set-aside decision making is discussed and recommendations are made for the genetic characteristics of set-aside sites. A checklist for environmental regulators forms a guide to aid decision making on the suitability of set-aside design and assessment using genetic tools. This non-technical primer document represents the views of participants in the VentBase 2014 workshop.

Biogeography of the fire salamander (Salamandra salamandra, L.) in Portugal

Dissertação de mest., Biologia Marinha, Faculdade de Ciências do Mar e do Ambiente, Universidade do Algarve, 2008

Salamandra salamandra (Amphibia: Caudata: Salamandridae) in Portugal: not all black and yellow

The fire salamander complex is quite diverse in the Iberian Peninsula where nine subspecies of Salamandra salamandra are currently recognized. Here, we analysed the geographical distribution of the subspecies S. s. gallaica and S. s. crespoi using partial sequences of the mitochondrial cytochrome b gene of 168 individuals from 12 locations in Portugal. Our results support the existence of a deep lineage divergence between the two subspecies, with non-overlapping geographical distributions except in two contact zones: one in Sesimbra on the western coast, and another in Alcoutim on the southeastern border with Spain. Moreover, S. s. crespoi displays signs of gene flow among the sampled locations whereas S. s. gallaica shows evidence of some restriction to gene flow. Present-day genetic make-up of S. s. gallaica and S. s. crespoi is a result of past historical events, fine-tuned by contemporary Iberian geoclimate. Humid mountain areas were found to harbour increased genetic diversity possibly acting as past refugia during drier interglacial periods. To analyse wider geographical patterns and lineage splitting events within S. salamandra we performed a Bayesian dating analysis completing our data set with previously published sequences. The observed divergences were associated to successive biogeographic scenarios, and to other Iberian species showing similar trends.