X-Ray Repair Cross-Complementing Group 1 (XRCC1) Genetic Polymorphisms and Risk of Childhood Acute Lymphoblastic Leukemia: A Meta-Analysis

Background: Recently, there have been a number of studies on the association between XRCC1 polymorphisms and childhood acute lymphoblastic leukemia (ALL) risk. However, the results of previous reports are inconsistent. Thus, we performed a meta-analysis to clarify the effects of XRCC1 variants on childhood ALL risk. Methods: A meta-analysis was performed to examine the association between XRCC1 polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) and childhood ALL risk. We critically reviewed 7 studies with a total of 880 cases and 1311 controls for Arg399Gln polymorphism, 3 studies with a total of 345 cases and 554 controls for Arg280His polymorphism, and 6 studies with a total of 783 cases and 1180 controls for Arg194Trp polymorphism, respectively. Odds ratio (OR) and its 95% confidence interval (CI) were used. Results: Significant association between XRCC1 Arg399Gln polymorphism and childhood ALL risk was observed in total population analyses (OR additive model = 1.501, 95 % CI 1.112–2.026, P OR = 0.008; OR dominant model = 1.316, 95 % CI = 1.104–1.569, POR = 0.002) and Asian subgroup analyses (ORadditive model = 2.338, 95%CI = 1.254–4.359, POR = 0.008; ORdominant model = 2.108, 95%CI = 1.498–2.967, POR = 0.000). No association was detected in Caucasians, Metizo and mixed populations. Ethnicity was considered as a significant source of heterogeneity in the meta-regression model. For the other two XRCC1 polymorphisms, no association with childhood ALL risk was found

CCL3L1 Copy Number Variation and Susceptibility to HIV-1 Infection: A Meta-Analysis

Background: Although several studies have investigated whether CCL3L1 copy number variation (CNV) influences the risk of HIV-1 infection, there are still no clear conclusions. Therefore, we performed a meta-analysis using two models to generate a more robust estimate of the association between CCL3L1 CNV and susceptibility to HIV-1 infection. Methods: We divided the cases and controls into two parts as individuals with CCL3L1 gene copy number (GCN) above the population specific median copy number (PMN) and individuals with CCL3L1 GCN below PMN, respectively. Odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were given for the main analysis. We also conducted stratified analyses by ethnicity, age group and sample size. Relevant literatures were searched through PubMed and ISI Web of Knowledge up t

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

Relationships between Gene Expression and Brain Wiring in the Adult Rodent Brain

We studied the global relationship between gene expression and neuroanatomical connectivity in the adult rodent brain. We utilized a large data set of the rat brain “connectome” from the Brain Architecture Management System (942 brain regions and over 5000 connections) and used statistical approaches to relate the data to the gene expression signatures of 17,530 genes in 142 anatomical regions from the Allen Brain Atlas. Our analysis shows that adult gene expression signatures have a statistically significant relationship to connectivity. In particular, brain regions that have similar expression profiles tend to have similar connectivity profiles, and this effect is not entirely attributable to spatial correlations. In addition, brain regions which are connected have more similar expression patterns. Using a simple optimization approach, we identified a set of genes most correlated with neuroanatomical connectivity, and find that this set is enriched for genes involved in neuronal development and axon guidance. A number of the genes have been implicated in neurodevelopmental disorders such as autistic spectrum disorder. Our results have the potential to shed light on the role of gene expression patterns in influencing neuronal activity and connectivity, with potential applications to our understanding of brain disorders. Supplementary data are available at http://www.chibi.ubc.ca/ABAMS

Genetic Differentiation, Structure, and a Transition Zone among Populations of the Pitcher Plant Moth Exyra semicrocea: Implications for Conservation

Pitcher plant bogs, or carnivorous plant wetlands, have experienced extensive habitat loss and fragmentation throughout the southeastern United States Coastal Plain, resulting in an estimated reduction to <3% of their former range. This situation has lead to increased management attention of these habitats and their carnivorous plant species. However, conservation priorities focus primarily on the plants since little information currently exists on other community members, such as their endemic arthropod biota. Here, we investigated the population structure of one of these, the obligate pitcher plant moth Exyra semicrocea (Lepidoptera: Noctuidae), using mitochondrial cytochrome c oxidase subunit I (COI) gene sequences. Examination of 221 individuals from 11 populations across eight southeastern US states identified 51 unique haplotypes. These haplotypes belonged to one of two divergent (∼1.9–3.0%) lineages separated by the Mississippi alluvial plain. Populations of the West Gulf Coastal Plain exhibited significant genetic structure, contrasting with similarly distanced populations east of the Mississippi alluvial plain. In the eastern portion of the Coastal Plain, an apparent transition zone exists between two regionally distinct population groups, with a well-established genetic discontinuity for other organisms coinciding with this zone. The structure of E. semicrocea appears to have been influenced by patchy pitcher plant bog habitats in the West Gulf Coastal Plain as well as impacts of Pleistocene interglacials on the Apalachicola-Chattahoochee-Flint River Basin. These findings, along with potential extirpation of E. semicrocea at four visited, but isolated, sites highlight the need to consider other endemic or associated community members when managing and restoring pitcher plant bog habitats

Paleodistributions and Comparative Molecular Phylogeography of Leafcutter Ants (Atta spp.) Provide New Insight into the Origins of Amazonian Diversity

The evolutionary basis for high species diversity in tropical regions of the world remains unresolved. Much research has focused on the biogeography of speciation in the Amazon Basin, which harbors the greatest diversity of terrestrial life. The leading hypotheses on allopatric diversification of Amazonian taxa are the Pleistocene refugia, marine incursion, and riverine barrier hypotheses. Recent advances in the fields of phylogeography and species-distribution modeling permit a modern re-evaluation of these hypotheses. Our approach combines comparative, molecular phylogeographic analyses using mitochondrial DNA sequence data with paleodistribution modeling of species ranges at the last glacial maximum (LGM) to test these hypotheses for three co-distributed species of leafcutter ants (Atta spp.). The cumulative results of all tests reject every prediction of the riverine barrier hypothesis, but are unable to reject several predictions of the Pleistocene refugia and marine incursion hypotheses. Coalescent dating analyses suggest that population structure formed recently (Pleistocene-Pliocene), but are unable to reject the possibility that Miocene events may be responsible for structuring populations in two of the three species examined. The available data therefore suggest that either marine incursions in the Miocene or climate changes during the Pleistocene—or both—have shaped the population structure of the three species examined. Our results also reconceptualize the traditional Pleistocene refugia hypothesis, and offer a novel framework for future research into the area