Genotyping an Emiliania huxleyi (Prymnesiophyceae) bloom event in the North Sea reveals evidence of asexual reproduction

Due to the unprecedented rate at which our climate is changing, the ultimate consequence for many species is likely to be either extinction or migration to an alternate habitat. Certain species might, however, evolve at a rate that could make them resilient to the effects of a rapidly changing environment. This scenario is most likely to apply to species that have large population sizes and rapid generation times, such that the genetic variation required for adaptive evolution can be readily supplied. Emiliania huxleyi (Lohm.) Hay and Mohler (Prymnesiophyceae) is likely to be such a species as it is the most conspicuous extant calcareous phytoplankton species in our oceans with generation times of 1 day−1. Here we report on a validated set of microsatellites, in conjunction with the coccolithophore morphology motif genetic marker, to genotype 93 clonal isolates collected from across the world. Of these, 52 came from a single bloom event in the North Sea collected on the D366 UK Ocean Acidification cruise in June-July 2011. There were 26 multilocus genotypes (MLGs) encountered only once in the North Sea bloom and 8 MLGs encountered twice or up to six times. Each of these repeated MLGs exhibited Psex values of less than 0.05 indicating each repeated MLG was the product of asexual reproduction and not separate meiotic events. In addition, we show that the two most polymorphic microsatellite loci, EHMS37 and P01E05, are reporting on regions likely undergoing rapid genetic drift during asexual reproduction. Despite the small sample size, there were many more repeated genotypes than previously reported for other bloom-forming phytoplankton species, including a previously genotyped E. huxleyi bloom event. This study challenges our current assumption that sex is the predominant mode of reproduction during bloom events. Whilst genetic diversity is high amongst extant populations of E. huxleyi, the root cause for this diversity and ultimate fate of these populations still requires further examination. Nonetheless, we show that certain CMM genotypes are found everywhere; while others appear to have a regional bias.

Tracking the invasive history of the green alga Codium fragile ssp. tomentosoides

The spread of nonindigenous species into new habitats is having a drastic effect on natural ecosystems and represents an increasing threat to global biodiversity. In the marine environment, where data on the movement of invasive species is scarce, the spread of alien seaweeds represents a particular problem. We have employed a combination of plastid microsatellite markers and DNA sequence data from three regions of the plastid genome to trace the invasive history of the green alga Codium fragile ssp. tomentosoides. Extremely low levels of genetic variation were detected, with only four haplotypes present in the species’ native range in Japan and only two of these found in introduced populations. These invasive populations displayed a high level of geographical structuring of haplotypes, with one haplotype localized in the Mediterranean and the other found in Northwest Atlantic, northern European and South Pacific populations. Consequently, we postulate that there have been at least two separate introductions of C. fragile ssp. tomentosoides from its native range in the North Pacific.

Fitness reduction and potential extinction of wild populations of Atlantic salmon, Salmo salar, as a result of interactions with escaped farm salmon.

The high level of escapes from Atlantic salmon farms, up to two million fishes per year in the North Atlantic, has raised concern about the potential impact on wild populations. We report on a twogeneration experiment examining the estimated lifetime successes, relative to wild natives, of farm, F1 and F2 hybrids and BC1 backcrosses to wild and farm salmon. Offspring of farm and hybrids (i.e. all F1 , F2 and BC1 groups) showed reduced survival compared with wild salmon but grew faster as juveniles and displaced wild parr, which as a group were significantly smaller. Where suitable habitat for these emigrant parr is absent, this competition would result in reduced wild smolt production. In the experimental conditions, where emigrants survived downstream, the relative estimated lifetime success ranged from 2% (farm) to 89% (BC1 wild) of that of wild salmon, indicating additive genetic variation for survival . Wild salmon primarily returned to fresh water after one sea winter (1SW) but farm and hybrids produced proportionately more 2SW salmon. However, lower overall survival means that this would result in reduced recruitment despite increased 2SW fecundity. We thus demonstrate that interaction of farm with wild salmon results in lowered fitness, with repeated escapes causing cumulative fitness depression and potentially an extinction vortex in vulnerable populations.

Genetically monomorphic brown trout (Salmo trutta L.) populations as revealed by mitochondrial DNA, multi-locus and single-locus minisatellite (VNTR) analyses.

Normally, populations of brown trout are genetically highly variable. Two adjacent populations from NW Scotland, which had previously been found to be monomorphic for 46 protein-coding loci, were studied by higher resolution techniques. Analyses of mitochondrial DNA, multilocus DNA fingerprints and eight specific minisatellite loci revealed no genetic variation among individuals or genetic differences between the two populations. Continual low effective population sizes or severe repeated bottlenecks, as a result of low or variable recruitment, probably explain the atypical absence of genetic variation in these trout populations. Growth data do not provide any evidence of a reduction in fitness in trout from these populations.

Clinical traits of LRRK2-associated parkinson's disease in ireland: a link between familial and idiopathic PD

The role of genetics in parkinsonism has been confirmed over the last decade with the identification of genetic variation in seven genes, which are causative in familial forms of the disorder. A number of pathogenic mutations have been identified in the latest gene LRRK2, with a Gly2019Ser amino acid substitution identified in two siblings and one patient with idiopathic Parkinson's disease from Ireland. The clinical features resemble the idiopathic variant with a tremor predominant clinical picture shared by the siblings, slow progression of symptoms, and no observation of cognitive disturbance in all. The family and the sporadic individual were apparently not related and originated from different regions of Ireland, although haplotype analysis does suggest they share a common founder. The influence of the G2019S substitution on protein function and disease phenotype has yet to be fully resolved, but its elucidation will undoubtedly further our understanding of the mechanisms underlying Parkinson's disease.

Familial genes in sporadic disease: Common variants of a-Synuclein gene associate with Parkinson’s disease

Genetic variation of the alpha-synuclein gene (SNCA) is known to cause familial parkinsonism, however the role of SNCA variants in sporadic Parkinson's disease (PD) remains elusive. The present study identifies an association of common SNCA polymorphisms with disease susceptibility in a series of Irish PD patients. There is evidence for association with alternate regions, of protection and risk which may act independently/synergistically, within the promoter region (Rep1; OR: 0.59, 95% CI: 0.37-0.84) and the 3'UTR of the gene (rs356165; OR: 1.67, 95% CI: 1.08-2.58). Given previous reports of association a collaborative effort is required which may exploit global linkage disequilibrium patterns for SNCA and standardise polymorphic markers used in each population. It is now crucial to identify the susceptibility allele and elucidate its functionality which may generate a therapeutic target for PD.

Association between polymorphism in regulatory region of gene encoding tumour necrosis factor alpha and risk of Alzheimer's disease and vascular dementia: a case-control study

BACKGROUND: Deposition of beta-amyloid in the brains of patients with Alzheimer's disease is thought to precede a chain of events that leads to an inflammatory response by the brain. We postulated that genetic variation in the regulatory region of the gene for the proinflammatory cytokine tumour necrosis factor alpha (TNF-alpha) leads to increased risk of Alzheimer's disease and vascular dementia. METHODS: A polymorphism in the regulatory region of the TNF-alpha gene was analysed in a case-control study. The polymorphism (C-850T) was typed in 242 patients with sporadic Alzheimer's disease, 81 patients with vascular dementia, 61 stroke patients without dementia, and 235 normal controls. These groups of individuals were also genotyped for the apolipoprotein E polymorphism, and the vascular dementia and stroke groups were typed at the HLA-DR locus. FINDINGS: The distribution of TNF-alpha genotypes in the vascular dementia group differed significantly from that in the stroke and normal control groups, giving an odds ratio of 2.51 (95% CI 1.49-4.21) for the development of vascular dementia for individuals with a CT or TT genotype. Logistic regression analysis indicated that the possession of the T allele significantly increased the risk of Alzheimer's disease associated with carriage of the apolipoprotein E epsilon4 allele (odds ratio 2.73 [1.68-4.44] for those with apolipoprotein E epsilon4 but no TNF-alpha T, vs 4.62 [2.38-8.96] for those with apolipoprotein E epsilon4 and TNF-alpha T; p=0.03). INTERPRETATION: Possession of the TNF-alpha T allele significantly increases the risk of vascular dementia, and increases the risk of Alzheimer's disease associated with apolipoprotein E. Although further research is needed, these findings suggest a potential role for anti-inflammatory therapy in vascular dementia and Alzheimer's disease, and perhaps especially in patients who have had a stroke.

The Genetics of Postglacial Colonization and Peripherality in Northwestern Populations of the Spring Peeper, Pseudacris crucifer

Glaciation over the Pleistocene induced dramatic range fluctuations for species across North America such that postglacial recolonization by southern refugial lineages has characterized the genetic structure of northern North American species. Based on the leading edge model of postglacial range expansion, dispersal and rapid population growth in these northern taxa is expected to produce vast areas of genetic homogeneity. Previous work on the widely distributed spring peeper (Pseudacris crucifer) revealed six distinct mitochondrial lineages that diverged between 3-11 mya, expanding and contracting with glacial cycles. Beginning 16,000 yBP, receding glaciers permitted Eastern lineage refugia residing in the southern Appalachians to migrate northward into the St. Lawrence Valley then westward through most of central Canada. Peripheral populations at the northwestern range limit of P. crucifer in central Manitoba are likely descended from this westward expanding Eastern lineage. According to the central-marginal hypothesis, founder effects from colonization as well as limited gene flow is expected to reveal genetic differentiation and lower genetic diversity in peripheral populations. The goal of my study is to further our understanding of peripheral range dynamics in peripheral Manitoba populations of P. crucifer by determining their genetic affinity and diversity relative to more central populations in Ontario and Minnesota. In this study I amplified and aligned cytochrome b sequences from sample sites across central Manitoba to reconstruct a Bayesian phylogeny for P. crucifer; additionally, microsatellite loci were genotyped to estimate genetic diversity. Results from this study affirmed Eastern lineage descent for peripheral Manitoba sites by aligning with Ontario. Initial colonization by the Interior lineage between glacial retreat and the appearance of arid vicariance events may explain the apparent introgression of non-Eastern lineages in Manitoba. However, genetic diversity measured in expected heterozygosity (H¬e) was not found to be significantly different in Manitoba genotypes. Greater isolation by distance and inbreeding relative to Ontario and Minnesota is likely the primary driver of genetic variation in these sites. Further sampling is necessary to generate a more complete genetic population structure for P. crucifer.

Further assessment of the complement component 2 and factor B region associated with age-related macular degeneration

PURPOSE. Polymorphic variation in genes involved in regulation of the complement system has been implicated as a major cause of genetic risk, in addition to the LOC387715/HTRA1 locus and other environmental influences. Previous studies have identified polymorphisms in the complement component 2 (CC2) and factor B (CFB) genes, as potential functional variants associated with AMD, in particular CFB R32Q and CC2 rs547154, both of which share strong linkage disequilibrium (LD). METHODS. Data derived from the HapMap Project were used to select 18 haplotype-tagging SNPs across the extended CC2/ CFB region for genotyping, to measure the strength of LD in 318 patients with neovascular AMD and 243 age-matched control subjects to identify additional potential functional variants in addition to those originally reported. RESULTS. Strong LD was measured across this region as far as the superkiller viralicidic activity 2-like gene (SKIV2L). Nine SNPs were identified to be significantly associated with the genetic effect observed at this locus. Of these, a nonsynonymous coding variant SKIV2L R151Q (rs438999; OR, 0.48; 95% confidence interval [CI], 0.31- 0.74; P < 0.001), was in strong LD with CFB R32Q, rs641153 (r2 = 0.95) and may exert a functional effect. When assessed within a logistic regression model measuring the effects of genetic variation at the CFH and LOC387715/HTRA1 loci and smoking, the effect remained significant (OR, 0.38; 95% CI, 0.22- 0.65; P < 0.001). Additional variation identified within this region may also confer a weaker but independent effect and implicate additional genes within the pathogenesis of AMD. CONCLUSIONS. Because of the high level of LD within the extended CC2/CFB region, variation within SKIV2L may exert a functional effect in AMD. Copyright © Association for Research in Vision and Ophthalmology.

Understanding marine reserve function in a seascape genetics context: Nucella lapillus in Strangford Lough (Northern Ireland) as an example

A conservation priority in the marine environment is the establishment of ecologically coherent reserve networks. Since these networks will integrate existent reserves, an understanding of spatial genetic diversity and genetic connectivities between areas is necessary. Using Strangford Lough marine nature reserve (MNR) as a model, spatial genetic analyses were employed to evaluate the function of the lough. Samples of the marine gastropod Nucella lapillus (L.) from 7 locations in the reserve and adjacent areas were screened at 6 microsatellites. Genetic variation was temporally stable. Significant genetic structuring (F-ST = 0.133) was observed among samples. Genetic divergence and isolation by distance indicated reduced gene flow between the marine reserve and coastal samples relative to that between adjacent coastal samples. Partitioning of genetic variation between the reserve and coast was significant (AMOVA, 7.45%, p

Radiation and the genome: from risks to opportunities for therapeutic exploitation

On 1 December 2009, the Radiation and Cancer Biology Committee of the British Institute of Radiology (BIR) held a one-day conference on the theme of radiation and the genome. Talks covered genomic instability (its importance for radiation-induced carcinogenesis and potential for exploitation in the development of novel chemoradiotherapy combinations) and the prospects of exploiting knowledge of the genome to understand how individual genetic variation can impact on a patient's likelihood of developing toxicity following radiotherapy. The meeting also provided an overview of stem cell biology and its relevance for radiotherapy in terms of both tumour (somatic) and normal tissue (germline) sensitivity to radiation. Moreover, the possibility of manipulating stem cells to reduce radiation-induced normal tissue damage was considered.

Evaluation of Five Interleukin Genes for Association with End-Stage Renal Disease in White Europeans

Background: Genetic variation within interleukin genes has been reported to be associated with end-stage renal disease (ESRD). These findings have not been consistently replicated. No study has yet reported the comprehensive investigation of IL1A, IL1B, IL1RN, IL6 and IL10 genes. Methods: 664 kidney transplant recipients (cases) and 577 kidney donors (controls) were genotyped to establish if common variants in interleukin genes are associated with ESRD. Single nucleotide polymorphism (SNP) genotype data for each gene were downloaded for a northern and western European population from the International HapMap Project. Haploview was used to visualize linkage disequilibrium and select tag SNPs. Thirty SNPs were genotyped using MassARRAY (R) iPLEX Gold technology and data were analyzed using the chi(2) test for trend. Independent replication was conducted in 1,269 individuals with similar phenotypic characteristics. Results: Investigating all common variants in IL1A, IL1B, IL1RN, IL6 and IL10 genes revealed a statistically significant association (rs452204 p(empirical) = 0.02) with one IL1RN variant and ESRD. This IL1RN SNP tags three other variants, none of which have previously been reported to be associated with renal disease. Independent replication in a separate transplant population of comparable size did not confirm the original observation. Conclusions: Common variants in these five candidate interleukin genes are not major risk factors for ESRD in white Europeans. Copyright (C) 2010 S. Karger AG, Basel

A Population-Based Study of IGF Axis Polymorphisms and the Esophageal Inflammation, Metaplasia, Adenocarcinoma Sequence

BACKGROUND & AIMS: Insulin-like growth factor (IGF) axis plays a key role in cell development, proliferation, and survival and is implicated in the etiology of several cancers. Few studies have examined the relationship between genetic variation of this axis and esophageal adenocarcinoma (EAC) or its precursors. METHODS: In a population-based case-control study, we investigated the association of common polymorphisms of IGF-1, IGF-2, IGF-1 receptor, IGF binding protein -3, growth hormones (GH) 1 and GH2, and GH receptor with reflux esophagitis (RE), Barrett esophagus (BE), and EAC. Two hundred and thirty RE, 224 BE, 227 EAC cases, and 260 controls were studied. Gene polymorphisms were identified using publicly available online resources; 102 IGF axis tag and putatively functional single-nucleotide polymorphisms (SNPs) were analyzed using MassARRAY iPLEX and Taqman assays. Results were analyzed using Haploview.
RESULTS: Three polymorphisms were disease-associated. IGF1 SNP rs6214 was associated with BE (adjusted P = .039). Using GG genotype as reference, odds ratio for BE in AA (wild-type) was 0.43 (95% confidence interval [CI], 0.24-0.75). GH receptor SNP rs6898743 was associated with EAC (adjusted P = .0112). With GG as reference, odds ratio for EAC in CC (wildtype) genotype was 0.42 (95% CI, 0.23-0.76). IGF1 (CA)(17) 185-bp allele was associated with RE (adjusted P = .0116). Using IGF1(non17) as reference, odds ratio for RE in IGF1(17) carriers was 7.29 (95% CI, 1.57-46.7).
CONCLUSIONS: In this study, 3 polymorphisms of IGF genes were associated with EAC or its precursors. These polymorphisms may be markers of disease risk; independent validation of our findings is required. These results suggest the IGF pathway is involved in EAC development.

Heritability of immune function in the caterpillar Spodoptera littoralis

Phenoloxidase (PO) is believed to be a key mediator of immune function in insects and has been implicated both in non-self recognition and in resistance to a variety of parasites and pathogens, including baculoviruses and parasitoids. Using larvae of the Egyptian cotton leafworm, Spodoptera littoralis, we found that despite its apparent importance, haemolymph PO activity varied markedly between individuals, even amongst insects reared under apparently identical conditions. Sib-analysis methods were used to determine whether individuals varied genetically in their PO activity, and hence in one aspect of immune function. The heritability estimate of haemolymph PO activity was high (h 2 = 0.690 +/- 0.069), and PO activity in the haemolymph was strongly correlated with PO activity in both the cuticle and midgut; the sites of entry for most parasites and pathogens. Haemolymph PO activity was also strongly correlated with the degree to which a synthetic parasite (a small piece of nylon monofilament) was encapsulated and melanized (r = 0.622 +/- 0.142), suggesting that the encapsulation response is also heritable. The mechanism maintaining this genetic variation has yet to be elucidated.

Association Analysis of the PIP4K2A Gene on Chromosome 10p12 and Schizophrenia in the Irish Study of High Density Schizophrenia Families (ISHDSF) and the Irish Case-Control Study of Schizophrenia (ICCSS)

Molecular studies support pharmacological evidence that phosphoinositide signaling is perturbed in schizophrenia and bipolar disorder. The phosphatidylinositol-4-phosphate-5-kinase type-II alpha (PIP4K2A) gene is located on chromosome 10p12. This region has been implicated in both diseases by linkage, and PIP4K2A directly by association. Given linkage evidence in the Irish Study of High Density Schizophrenia Families (ISHDSF) to a region including 10p12, we performed an association study between genetic variants at PIP4K2A and disease. No association was detected through single-marker or haplotype analysis of the whole sample. However, stratification into families positive and negative for the ISHDSF schizophrenia high-risk haplotype (HRH) in the DTNBP1 gene and re-analysis for linkage showed reduced amplitude of the 10p12 linkage peak in the DTNBP1 HRH positive families. Association analysis of the stratified sample showed a trend toward association of PIP4K2A SNPs rs1417374 and rs1409395 with schizophrenia in the DTNBP1 HRH positive families. Despite this apparent paradox, our data may therefore suggest involvement of PIP4K2A in schizophrenia in those families for whom genetic variation in DTNBP1 appears also to be a risk factor. This trend appears to arise from under-transmission of common alleles to female cases. Follow-up association analysis in a large Irish schizophrenia case-control control sample (ICCSS) showed significant association with disease of a haplotype comprising these same SNPs rs1417374-rs1409395, again more so in affected females, and in cases with negative family history of the disease. This study supports a minor role for PIP4K2A in schizophrenia etiology in the Irish population. (C) 2009 Wiley-Liss, Inc.