MedWorm: Genetics Top 20

Antidepressant Treatment for Acute Bipolar Depression: An Update

Comparative and Functional Genomics — Fri, 27 Jan 2012 14:47:07 +0100

Conclusions. Antidepressants probably have no substantial role in acute bipolar depression. However, in light of conflicting results between studies, more well-designed trials are warranted. (Source: Comparative and Functional Genomics)

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Altered mTOR signaling and enhanced CYFIP2 expression levels in subjects with Fragile X syndrome

Genes, Brain and Behavior — Fri, 27 Jan 2012 14:38:35 +0100

Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and autism. The protein (FMRP) encoded by the fragile X mental retardation gene (FMR1), is an RNA‐binding protein linked to translational control. Recently, in the Fmr1 knockout mouse model of FXS, dysregulated translation initiation signaling was observed. To investigate whether an altered signaling was also a feature of subjects with FXS compared to typical developing controls, we isolated total RNA and translational control proteins from lymphocytes of subjects from both groups (38 FXS and 14 TD). Although we did not observe any difference in the expression level of mRNAs for translational initiation control proteins isolated from participant with FXS, we found increased phosphorylation of the mammal...

Tests of linkage and allelic association between markers in the 1p36 PRKCZ (Protein Kinase C Zeta) gene region and bipolar affective disorder

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics — Mon, 09 Jan 2012 05:00:00 +0100

AbstractThree linkage studies of families with multiple cases of bipolar disorder and/or unipolar affective disorder have confirmed the involvement of the chromosome 1p36 region in the etiology of affective disorders with LOD scores of 2.7, 3.6, and 3.97. We investigated the protein kinase C zeta gene (PRKCZ) as a susceptibility locus for bipolar disorder because it is highly brain expressed and is localized close to the marker D1S243 which was linked to affective disorder in a single large UCL bipolar disorder family with a LOD of 3.1. PRKCZ encodes an unusual type of protein kinase which affects axonal differentiation through Wnt‐signaling. We genotyped four microsatellite markers and nine single nucleotide polymorphism (SNP) markers within or near the PRKCZ gene in the UCL case–cont...

Urinary Bisphenol A and Hypertension in a Multiethnic Sample of US Adults

Comparative and Functional Genomics — Fri, 27 Jan 2012 14:47:07 +0100

Conclusions. Urinary BPA levels are associated with hypertension, independent of traditional risk factors. (Source: Comparative and Functional Genomics)

Genotoxicity, cytotoxicity and toxicological evaluation of whole plant extracts of the medicinal plant Phyllanthus niruri (Phyllanthaceae).

Genetics and Molecular Research — Fri, 03 Feb 2012 11:24:05 +0100

We examined the geno-, cyto- and overall toxicity of P. niruri whole plant ethanolic extract. The extract was administered as a single dose of 30 or 300 mg/kg to laboratory rats by gavage, accompanied by negative (0.9% saline) and positive (10 mg/mL N-ethyl-N-nitrosourea) controls that were injected intramuscularly 48 h after extract administration. The ratio of polychromatic (PCE)/normochromatic erythrocytes (NCE) from femur bone marrow was scored for genotoxicity. Cytotoxicity was determined using descending concentrations (0.2-0.0125 g/mL) of the extract incubated with peripheral blood mononuclear cells. Lactate dehydrogenase release from damaged cells was determined and the CC(50) calculated. Subchronic administration of the extract at 30 or 300 mg/kg was done for 90 days to determine ...

Rare germline mutations in PALB2 and breast cancer risk: A population‐based study

Human Mutation — Sun, 15 Jan 2012 03:43:21 +0100

AbstractGermline mutations in the PALB2 gene are associated with an increased risk of developing breast but little is known about the frequencies of rare variants in PALB2 and the nature of the variants that influence risk. We selected participants recruited to the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study and screened lymphocyte DNA from cases with contralateral breast cancer (n = 559) and matched controls with unilateral breast cancer (n = 565) for PALB2 mutations. Five pathogenic PALB2 mutations were identified among the cases (0.9%) versus none among the controls (p = 0.04). The first degree female relatives of these five carriers demonstrated significantly higher incidence of breast cancer than relatives of non‐carrier cases, indicating that pathogenic P...

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Polymorphisms of the TIM-1 gene are associated with rheumatoid arthritis in the Chinese Hui minority ethnic population.

Genetics and Molecular Research — Fri, 03 Feb 2012 11:24:05 +0100

Polymorphisms of the TIM-1 gene are associated with rheumatoid arthritis in the Chinese Hui minority ethnic population. Genet Mol Res. 2012;11(1):61-9 Authors: Xu JR, Yang Y, Liu XM, Sun JY, Wang YJ Abstract The T-cell immunoglobulin and mucin domain 1 (TIM-1) is known to be associated with susceptibility to rheumatoid arthritis (RA). We investigated the association of four single-nucleotide polymorphisms (SNPs) in the promoter region of the TIM-1 gene with susceptibility to RA in a Chinese Hui ethnic minority group. Using RFLP or sequence specific primer-PCR, 118 RA patients and 118 non-arthritis control individuals were analyzed for the -1637A>G, -1454G>A, -416G>C, and -232A>G SNPs in the TIM-1 gene. The polymorphisms -232A>G and -1637A>G in the promoter...

GluN1 hypomorph mice exhibit wide‐ranging behavioral alterations

Genes, Brain and Behavior — Fri, 03 Feb 2012 14:26:39 +0100

The psychotomimetic effects of N‐methyl‐D‐aspartate receptor (NMDA) antagonists such as ketamine and phencyclidine suggest a role for reduced NMDA receptor‐mediated neurotransmission in schizophrenia. GluN1 ‘‘hypomorph'' (GluN1hypo) mice exhibit reduced NMDA receptor expression and have been suggested as a mouse model of schizophrenia. However, NMDA receptors are ubiquitous and are implicated in many physiological and pathological processes. The GluN1hypo mice have a global reduction of NMDA receptors and the consequences of such a global manipulation are likely to be wide‐ranging. We therefore assessed GluN1hypo mice on a battery of behavioral tests, including tests of naturalistic behaviors, anxiety and cognition. GluN1hypo mice exhibited impairments on all tests of cogniti...

DICER1 in ovarian cancers

Nature Genetics — Fri, 27 Jan 2012 05:00:00 +0100

Nature Genetics 44, 120 (2012). doi:10.1038/ng.1095 Author: Kyle Vogan (Source: Nature Genetics)

Evolution of the porcine (Sus scrofa domestica) immunoglobulin kappa locus through germline gene conversion

Immunogenetics — Tue, 22 Nov 2011 17:57:32 +0100

Abstract Immunoglobulin (IG) gene rearrangement and expression are central to disease resistance and health maintenance in animals. The IG kappa (IGK) locus in swine (Sus scrofa domestica) contributes to approximately half of all antibody molecules, in contrast to many other Cetartiodactyla, whose members provide the majority of human dietary protein and in which kappa locus utilization is limited. The porcine IGK variable locus is 27.9 kb upstream of five IG kappa J genes (IGKJ) which are separated from a single constant gene (IGKC) by 2.8 kb. Fourteen variable genes (IGKV) were identified, of which nine are functional and two are open reading frame (ORF). Of the three pseudogenes, IGKV3-1 contains a frameshift and multiple stop codons, IGKV7-2 contains multiple ...

American Journal of Medical Genetics Part A: Volume 158A, Number 2, February 2012

American Journal of Medical Genetics Part A — Sat, 21 Jan 2012 14:22:20 +0100

AbstractDynamic MRIs showing changes over time in 2 patients with progressive cerebellar tonsillar ectopia who have a disorder of brain overgrowth. See article by Mirzaa et al. in this issue. (Source: American Journal of Medical Genetics Part A)

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Coordinated changes in AHRR methylation in lymphoblasts and pulmonary macrophages from smokers

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics — Mon, 09 Jan 2012 05:00:00 +0100

AbstractSmoking is associated with a wide variety of adverse health outcomes including cancer, chronic obstructive pulmonary disease, diabetes, depression, and heart disease. Unfortunately, the molecular mechanisms through which these effects are conveyed are not clearly understood. To examine the potential role of epigenetic factors in these processes, we examined the relationship of smoking to genome wide methylation and gene expression using biomaterial from two independent samples, lymphoblast DNA and RNA (n = 119) and lung alveolar macrophage DNA (n = 19). We found that in both samples current smoking status was associated with significant changes in DNA methylation, in particular at the aryl hydrocarbon receptor repressor (AHRR), a known tumor suppressor. Both baseline DNA me...

Mannose‐binding lectin genotype and serum levels in patients with chronic and allergic pulmonary aspergillosis

International Journal of Immunogenetics — Mon, 09 Jan 2012 17:56:49 +0100

SummarySeveral studies suggest mannose‐binding lectin (MBL) deficiency is associated with various manifestations of aspergillosis. MBL serum levels and function are genetically determined, but levels rise during inflammation. We address the relative frequency of deficient genotypes, the relationship between serum level and genotype and both age and disease manifestations in patients with chronic pulmonary (CPA) and allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS). DNA was extracted from blood samples, and MBL2 genotyping was performed using the INNO‐LiPA MBL2 kit. Serum MBL concentrations were determined using ELISA. One hundred and eight patients were evaluated, 70 (65%) with CPA, 38 (35%) with allergic disease (ABPA, SAFS or undefined)...

SEPT12 mutations cause male infertility with defective sperm annulus

Human Mutation — Sat, 21 Jan 2012 14:25:08 +0100

We report the identification of two missense SEPT12 mutations, c.266C>T/p.Thr89Met and c.589G>A/p.Asp197Asn, in infertile men. Both mutations are located inside the GTPase domain and may alter the protein structure as suggested by in silico modeling. The p.Thr89Met mutation (SEPT12T89M) significantly reduced GTP hydrolytic activity, and the p.Asp197Asn mutation (SEPT12D197N) interfered with GTP binding. Both mutant SEPT12 proteins restricted the filament formation of the wild‐type SEPT12 in a dose‐dependent manner. The patient carrying SEPT12D197N presented with oligo‐asthenozoospermia while the SEPT12T89M patient had astheno‐teratozoospermia. The characteristic sperm pathology of the SEPT12D197N patient included defective annulus with bent tail and loss of SEPT12 from the an...

Pedigree‐ and marker‐based methods in the estimation of genetic diversity in small groups of Holstein cattle

Journal of Animal Breeding and Genetics — Fri, 27 Jan 2012 14:47:26 +0100

SummaryGenetic diversity is often evaluated using pedigree information. Currently, diversity can be evaluated in more detail over the genome based on large numbers of SNP markers. Pedigree‐ and SNP‐based diversity were compared for two small related groups of Holstein animals genotyped with the 50 k SNP chip, genome‐wide, per chromosome and for part of the genome examined. Diversity was estimated with coefficient of kinship (pedigree) and expected heterozygosity (SNP). SNP‐based diversity at chromosome regions was determined using 5‐Mb sliding windows, and significance of difference between groups was determined by bootstrapping. Both pedigree‐ and SNP‐based diversity indicated more diversity in one of the groups; 26 of the 30 chromosomes showed significantly more diversity...

Molecular Characterization and Physical Mapping of Two Classes of 5S rDNA in the Genomes of Gymnotus sylvius and G. inaequilabiatus (Gymnotiformes, Gymnotidae)

Cytogenetic and Genome Research — Tue, 24 Jan 2012 14:44:01 +0100

Cytogenet Genome Res (DOI:10.1159/000335658) (Source: Cytogenetic and Genome Research)

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Reciprocal translocations in cattle: frequency estimation

Journal of Animal Breeding and Genetics — Sun, 15 Jan 2012 03:45:06 +0100

SummaryChromosomal anomalies, like Robertsonian and reciprocal translocations, represent a big problem in cattle breeding as their presence induces, in the carrier subjects, a well‐documented fertility reduction. In cattle, reciprocal translocations (RCPs, a chromosome abnormality caused by an exchange of material between non‐homologous chromosomes) are considered rare as to date only 19 reciprocal translocations have been described. In cattle, it is common knowledge that the Robertsonian translocations represent the most common cytogenetic anomalies, and this is probably due to the existence of the endemic 1;29 Robertsonian translocation. However, these considerations are based on data obtained using techniques that are unable to identify all reciprocal translocations, and thus, their...

The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients [RESEARCH]

Genome Research — Fri, 20 Jan 2012 05:00:00 +0100

Hepatitis B virus (HBV) infection is a leading risk factor for hepatocellular carcinoma (HCC). HBV integration into the host genome has been reported but its scale, impact and contribution to HCC development is not clear. Here, we sequenced the tumor and non-tumor genomes (>80X coverage) and transcriptomes of four HCC patients and identified 255 HBV integration sites. Increased sequencing to 240X coverage revealed a proportionally higher number of integration sites. Clonal expansion of HBV-integrated hepatocytes was found specifically in tumor samples. We observe a diverse collection of genomic perturbations near viral integration sites, including direct gene disruption, viral promoter-driven human transcription, viral-human transcript fusion and DNA copy number alteration. Thus, we rep...

Cucurbitacin E Induces G2/M Phase Arrest through STAT3/p53/p21 Signaling and Provokes Apoptosis via Fas/CD95 and Mitochondria-Dependent Pathways in Human Bladder Cancer T24 Cells

Comparative and Functional Genomics — Mon, 09 Jan 2012 18:04:58 +0100

Cucurbitacin E, a tetracyclic triterpenes compound extracted from cucurbitaceous plants, has been shown to exhibit anticancer and anti-inflammatory activities. The purpose of this study was to elucidate whether cucurbitacin E promotes cell cycle arrest and induces apoptosis in T24 cells and further to explore the underlying molecular mechanisms. The effects of cucurbitacin E on T24 cell's growth and accompanied morphological changes were examined by MTT assay and a phase-contrast microscope. DNA content, mitochondrial membrane potential (ΔΨm) and annexin V/PI staining were determined by flow cytometry. The protein levels were measured by Western blotting. Our results demonstrated that cucurbitacin E-induced G2/M arrest was associated with a marked increase in the levels o...

Announcement

Theriogenology — Sun, 15 Jan 2012 03:44:38 +0100

February 2012 Announcement and Call for Abstracts (Source: Theriogenology)