Chloroplast microsatellites: measures of genetic diversity and the effect of homoplasy

Chloroplast microsatellites have been widely used in population genetic studies of conifers in recent years. However, their haplotype configurations suggest that they could have high levels of homoplasy, thus limiting the power of these molecular markers. A coalescent-based computer simulation was used to explore the influence of homoplasy on measures of genetic diversity based on chloroplast microsatellites. The conditions of the simulation were defined to fit isolated populations originating from the colonization of one single haplotype into an area left available after a glacial retreat. Simulated data were compared with empirical data available from the literature for a species of Pinus that has expanded north after the Last Glacial Maximum. In the evaluation of genetic diversity, homoplasy was found to have little influence on Nei's unbiased haplotype diversity (H(E)) while Goldstein's genetic distance estimates (D2sh) were much more affected. The effect of the number of chloroplast microsatellite loci for evaluation of genetic diversity is also discussed

The hOGG1 Ser326Cys polymorphism and prostate cancer risk: a meta-analysis of 2584 cases and 3234 controls

<p>Abstract</p> <p>Background</p> <p>Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) Ser326Cys (rs1052133) has been implicated to alter the risk of prostate cancer, but the results are controversial.</p> <p>Methods</p> <p>Two investigators independently searched the Medline, and Cochrane Library up to June 7, 2011. Summary odds ratios (OR) and 95% confidence interval (CI) for Ser326Cys polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Review Manage, version 5.0 and Stata 10.0.</p> <p>Results</p> <p>A total of 8 independent studies, including 2584 cases and 3234 controls, were identified. Our analysis suggested that Ser326Cys was not associated with prostate cancer risk in overall population. In the subgroup analysis, we detected the significant association between Ser326Cys polymorphism and decreased prostate risk in mixed population under additive model (OR = 0.67, 95% CI = 0.50-0.90, P = 0.007), recessive model (OR = 0.68, 95% CI = 0.51-0.91, P = 0.008), and Cys allele versus Ser allele (OR = 0.88, 95% CI = 0.78-0.98, P = 0.02). Subanalysis on Caucasian subjects demonstrated that Ser326Cys was not associated with prostate cancer risk.</p> <p>Conclusion</p> <p>This meta-analysis showed the evidence that hOGG1 Ser326Cys polymorphism was associated with a decreased risk of prostate cancer development in mixed populations.</p

A social network analysis of social cohesion in a constructed pride: Implications for ex situ reintroduction of the African Lion (Panthera leo)

Animal conservation practices include the grouping of captive related and unrelated individuals to form a social structure which is characteristic of that species in the wild. In response to the rapid decline of wild African lion (Panthera leo) populations, an array of conservational strategies have been adopted. Ex situ reintroduction of the African lion requires the construction of socially cohesive pride structures prior to wild release. This pilot study adopted a social network theory approach to quantitatively assess a captive pride's social structure and the relationships between individuals within them. Group composition (who is present in a group) and social interaction data (social licking, greeting, play) was observed and recorded to assess social cohesion within a released semi-wild pride. UCINET and SOCPROG software was utilised to represent and analyse these social networks. Results indicate that the pride is socially cohesive, does not exhibit random associations, and the role of socially influential keystone individuals is important for maintaining social bondedness within a lion pride. These results are potentially informative for the structure of lion prides, in captivity and in the wild, and could have implications for captive and wild-founder reintroductions

A systematic review of Vancouver B2 and B3 periprosthetic femoral fractures

Aims The aim of this study was to investigate the outcomes of Vancouver type B2 and B3 fractures by performing a systematic review of the methods of surgical treatment which have been reported. Materials and Methods A systematic search was performed in Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. For inclusion, studies required a minimum of ten patients with a Vancouver type B2 and/or ten patients with a Vancouver type B3 fracture, a minimum mean follow-up of two years and outcomes which were matched to the type of fracture. Studies were also required to report the rate of re-operation as an outcome measure. The protocol was registered in the PROSPERO database. Results A total of 22 studies were included based on the eligibility criteria, including 343 B2 fractures and 167 B3 fractures. The mean follow-up ranged from 32 months to 74 months. Of 343 Vancouver B2 fractures, the treatment in 298 (86.8%) involved revision arthroplasty and 45 (12.6%) were treated with internal fixation alone. A total of 37 patients (12.4%) treated with revision arthroplasty and six (13.3%) treated by internal fixation only underwent further re-operation. Of 167 Vancouver B3 fractures, the treatment in 160 (95.8%) involved revision arthroplasty and eight (4.8%) were treated with internal fixation without revision. A total of 23 patients (14.4%) treated with revision arthroplasty and two (28.6%) treated only with internal fixation required re-operation. Conclusion A significant proportion, particularly of B2 fractures, were treated without revision of the stem. These were associated with a higher rate of re-operation. The treatment of B3 fractures without revision of the stem resulted in a high rate of re-operation. This demonstrates the importance of careful evaluation and accurate characterisation of the fracture at the time of presentation to ensure the correct management. There is a need for improvement in the reporting of data in case series recording the outcome of the surgical treatment of periprosthetic fractures. We have suggested a minimum dataset to improve the quality of data in studies dealing with these fractures

Normosmic Congenital Hypogonadotropic Hypogonadism Due to TAC3/TACR3 Mutations: Characterization of Neuroendocrine Phenotypes and Novel Mutations

CONTEXT: TAC3/TACR3 mutations have been reported in normosmic congenital hypogonadotropic hypogonadism (nCHH) (OMIM #146110). In the absence of animal models, studies of human neuroendocrine phenotypes associated with neurokinin B and NK3R receptor dysfunction can help to decipher the pathophysiology of this signaling pathway. OBJECTIVE: To evaluate the prevalence of TAC3/TACR3 mutations, characterize novel TACR3 mutations and to analyze neuroendocrine profiles in nCHH caused by deleterious TAC3/TACR3 biallelic mutations. RESULTS: From a cohort of 352 CHH, we selected 173 nCHH patients and identified nine patients carrying TAC3 or TACR3 variants (5.2%). We describe here 7 of these TACR3 variants (1 frameshift and 2 nonsense deleterious mutations and 4 missense variants) found in 5 subjects. Modeling and functional studies of the latter demonstrated the deleterious consequence of one missense mutation (Tyr267Asn) probably caused by the misfolding of the mutated NK3R protein. We found a statistically significant (p<0.0001) higher mean FSH/LH ratio in 11 nCHH patients with TAC3/TACR3 biallelic mutations than in 47 nCHH patients with either biallelic mutations in KISS1R, GNRHR, or with no identified mutations and than in 50 Kallmann patients with mutations in KAL1, FGFR1 or PROK2/PROKR2. Three patients with TAC3/TACR3 biallelic mutations had an apulsatile LH profile but low-frequency alpha-subunit pulses. Pulsatile GnRH administration increased alpha-subunit pulsatile frequency and reduced the FSH/LH ratio. CONCLUSION: The gonadotropin axis dysfunction associated with nCHH due to TAC3/TACR3 mutations is related to a low GnRH pulsatile frequency leading to a low frequency of alpha-subunit pulses and to an elevated FSH/LH ratio. This ratio might be useful for pre-screening nCHH patients for TAC3/TACR3 mutations

Ancestral Informative Marker Selection and Population Structure Visualization Using Sparse Laplacian Eigenfunctions

Identification of a small panel of population structure informative markers can reduce genotyping cost and is useful in various applications, such as ancestry inference in association mapping, forensics and evolutionary theory in population genetics. Traditional methods to ascertain ancestral informative markers usually require the prior knowledge of individual ancestry and have difficulty for admixed populations. Recently Principal Components Analysis (PCA) has been employed with success to select SNPs which are highly correlated with top significant principal components (PCs) without use of individual ancestral information. The approach is also applicable to admixed populations. Here we propose a novel approach based on our recent result on summarizing population structure by graph Laplacian eigenfunctions, which differs from PCA in that it is geometric and robust to outliers. Our approach also takes advantage of the priori sparseness of informative markers in the genome. Through simulation of a ring population and the real global population sample HGDP of 650K SNPs genotyped in 940 unrelated individuals, we validate the proposed algorithm at selecting most informative markers, a small fraction of which can recover the similar underlying population structure efficiently. Employing a standard Support Vector Machine (SVM) to predict individuals' continental memberships on HGDP dataset of seven continents, we demonstrate that the selected SNPs by our method are more informative but less redundant than those selected by PCA. Our algorithm is a promising tool in genome-wide association studies and population genetics, facilitating the selection of structure informative markers, efficient detection of population substructure and ancestral inference

Hsa-miR-196a2 Rs11614913 Polymorphism Contributes to Cancer Susceptibility: Evidence from 15 Case-Control Studies

BACKGROUND: MicroRNAs (miRNAs) are a family of endogenous, small and noncoding RNAs that negatively regulate gene expression by suppressing translation or degrading mRNAs. Recently, many studies investigated the association between hsa-miR-196a2 rs11614913 polymorphism and cancer risk, which showed inconclusive results. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a meta-analysis of 15 studies that included 9,341 cancer cases and 10,569 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, individuals with the TC/CC genotypes were associated with higher cancer risk than those with the TT genotype (OR=1.18, 95% CI=1.03-1.34, P<0.001 for heterogeneity test). In the stratified analyses, we observed that the CC genotype might modulate breast cancer risk (OR=1.11, 95%CI=1.01-1.23, Pheterogeneity=0.210) and lung cancer risk (OR=1.25, 95%CI=1.06-1.46, Pheterogeneity=0.958), comparing with the TC/TT genotype. Moreover, a significantly increased risk was found among Asian populations in a dominant model (TC/CC versus TT, OR=1.24, 95% CI=1.07-1.43, Pheterogeneity=0.006). CONCLUSIONS: These findings supported that hsa-miR-196a2 rs11614913 polymorphism may contribute to the susceptibility of cancers

Evidence of two lineages of the dengue vector Aedes aegypti in the Brazilian Amazon, based on mitochondrial DNA ND4 gene sequences

Genetic variation was estimated in ten samples populations of Aedes aegypti from the Brazilian Amazon, by using a 380 bp fragment of the mitochocondrial NADH dehydrogenase subunit 4 (ND4) gene. A total of 123 individuals were analyzed, whereby 13 haplotypes were found. Mean genetic diversity was slightly high (h = 0.666 ± 0.029; π = 0.0115 ± 0.0010). Two AMOVA analyses indicated that most of the variation (~70%-72%) occurred within populations. The variation found among and between populations within the groups disclosed lower, but even so, highly significant values. FST values were not significant in most of the comparisons, except for the samples from Pacaraima and Rio Branco. The isolation by distance (IBD) model was not significant (r = 0.2880; p = 0.097) when the samples from Pacaraima and Rio Branco were excluded from the analyses, this indicating that genetic distance is not related to geographic distance. This result may be explained either by passive dispersal patterns (via human migrations and commercial exchange) or be due to the recent expansion of this mosquito in the Brazilian Amazon. Phylogenetic relationship analysis showed two genetically distinct groups (lineages) within the Brazilian Amazon, each sharing haplotypes with populations from West Africa and Asia

Expression of cyclooxygenase-2 (COX-2) in tumour and stroma compartments in cervical cancer: clinical implications

This study aims at investigating the relationship between cyclooxygenase-2 expression in tumour vs stroma inflammatory compartment and its possible clinical role. The study included 99 stage IB-IV cervical cancer patients: immunostaining of tumour tissue sections was performed with rabbit antiserum against cyclooxygenase-2. CD3, CD4, CD8, CD25, Mast Cell Tryptase monoclonal antibodies were used to characterise stroma inflammatory cells in nine cervical tumours. An inverse relation was found between cyclooxygenase-2 levels (cyclooxygenase-2 IDV) of tumour vs stroma compartment (r=−0.44, P<0.0001). The percentage of cases showing high tumour/stromal cyclooxygenase-2 IDV ratio was significantly higher in patients who did not respond to treatment (93.3%) with respect to patients with partial (60.5%), and complete (43.7%) response (P= 0.009). Cases with a high tumour/stroma cyclooxygenase-2 IDV ratio had a shorter overall survival rate than cases with a low tumour/stroma cyclooxygenase-2 IDV (P<0.0001). In the multivariate analysis advanced stage and the status of tumour/stroma cyclooxygenase-2 IDV ratio retained an independent negative prognostic role. The proportion of CD3+, CD4+, and CD25+ cells was significantly lower in tumours with high tumour/stroma cyclooxygenase-2 IDV ratio, while a higher percentage of mast cells was detected in tumours showing high tumour/stroma cyclooxygenase-2 IDV ratio. Our study showed the usefulness of assessing cyclooxygenase-2 status both in tumour and stroma compartment in order to identify cervical cancer patients endowed with a very poor chance of response to neoadjuvant therapy and unfavourable prognosis

A Common SMAD7 Variant Is Associated with Risk of Colorectal Cancer: Evidence from a Case-Control Study and a Meta-Analysis

<div><h3>Background</h3><p>A common genetic variant, rs4939827, located in <em>SMAD7</em>, was identified by two recent genome-wide association (GWA) studies to be strongly associated with the risk of colorectal cancer (CRC). However, the following replication studies yielded conflicting results.</p> <h3>Method and Findings</h3><p>We conducted a case-control study of 641 cases and 1037 controls in a Chinese population and then performed a meta-analysis, integrating our and published data of 34313 cases and 33251 controls, to clarify the relationship between rs4939827 and CRC risk. In our case-control study, the dominant model was significant associated with increased CRC risk [Odds Ratio (OR) = 1.46; 95% confidence interval (95% CI), 1.19–1.80]. The following meta-analysis further confirmed this significant association for all genetic models but with significant between-study heterogeneity (all <em>P</em> for heterogeneity <0.1). By stratified analysis, we revealed that ethnicity, sample size, and tumor sites might constitute the source of heterogeneity. The cumulative analysis suggested that evident tendency to significant association was seen with adding study samples over time; whilst, sensitive analysis showed results before and after removal of each study were similar, indicating the highly stability of the current results.</p> <h3>Conclusion</h3><p>Results from our case-control study and the meta-analysis collectively confirmed the significant association of the variant rs4939827 with increased risk of colorectal cancer. Nevertheless, fine-mapping of the susceptibility loci defined by rs4939287 should be imposed to reveal causal variant.</p> </div