ABCC10 (ATP-binding cassette, sub-family C (CFTR/MRP), member 10)

Review on ABCC10, with data on DNA/RNA, on the protein encoded and where the gene is implicated

Female responses to experimental removal of sexual selection components in Drosophila melanogaster

Despite the common assumption that multiple mating should in general be favored in males, but not in females, to date there is no consensus on the general impact of multiple mating on female fitness. Notably, very little is known about the genetic and physiological features underlying the female response to sexual selection pressures. By combining an experimental evolution approach with genomic techniques, we investigated the effects of single and multiple matings on female fecundity and gene expression. We experimentally manipulated the opportunity for mating in replicate populations of Drosophila melanogaster by removing components of sexual selection, with the aim of testing differences in short term post-mating effects of females evolved under different mating strategies

Divergence in transcriptional and regulatory responses to mating in male and female fruitflies

Mating induces extensive physiological, biochemical and behavioural changes in female animals of many taxa. In contrast, the overall phenotypic and transcriptomic consequences of mating for males, hence how they might differ from those of females, are poorly described. Post mating responses in each sex are rapidly initiated, predicting the existence of regulatory mechanisms in addition to transcriptional responses involving de novo gene expression. That post mating responses appear different for each sex also predicts that the genome-wide signatures of mating should show evidence of sex-specific specialisation. In this study, we used high resolution RNA sequencing to provide the first direct comparisons of the transcriptomic responses of male and female Drosophila to mating, and the first comparison of mating-responsive miRNAs in both sexes in any species. As predicted, the results revealed the existence of sex- and body part-specific mRNA and miRNA expression profiles. More genes were differentially expressed in the female head-thorax than the abdomen following mating, whereas the opposite was true in males. Indeed, the transcriptional profile of male head-thorax tissue was largely unaffected by mating, and no differentially expressed genes were detected at the most stringent significance threshold. A subset of ribosomal genes in females were differentially expressed in both body parts, but in opposite directions, consistent with the existence of body part-specific resource allocation switching. Novel, mating-responsive miRNAs in each sex were also identified, and a miRNA-mRNA interactions analysis revealed putative targets among mating-responsive genes. We show that the structure of genome-wide responses by each sex to mating is strongly divergent, and provide new insights into how shared genomes can achieve characteristic distinctiveness

P113

Heparansulfate (HS) is a glycosaminoglycan present on the cell surface and in the extracellular matrix, which interacts with diverse signal molecules and is essential for many physiological processes including embryonic development, cell growth, inflammation, and blood coagulation. d-glucuronyl C5-epimerase (GLCE) is a crucial enzyme in HS synthesis, converting d-glucuronic acid (GlcA) to l-iduronic acid (IdoA) to increase HS flexibility. Aberrant modification may result in wrong structure of polysaccharide chains of HS and defects of microenvironment associated with malignant transformation.We previously experimentally identified the GLCE polymorphism Ile597Val. Its localization close to the activity center of the enzyme and different physical parameters of the involved amino acids suggest that the polymorphism is functional. So, three different variants of GLCE dimers with different enzymatic activity may exist in heterozygous carriers. Bioinformatics’ search (PubMed resource) revealed interracial variations in allele frequency distribution. Unusual high frequency of allele G was shown for black race (45%) compared with white race (17%). Taking into account the increased resistance of negroid race to breast cancer, we assume a potential involvement of the GLCE polymorphism in breast cancer. Aim: The estimation of effects of GLCE functional polymorphism A2017G (Ile597Val) on the gene expression levels in normal and breast cancer cells and LOH in breast tumors. Materials and methods: Breast cancer patients (n = 144.) had histologically verified diagnoses. Blood and breast cancer tissue samples as well as matched control tissues were collected from each patient during surgery. Genomic DNA was isolated by phenol extraction. Total RNA was isolated by TRIZol, RNA quantity was accessed by Qubit instrument with appropriate reagents and cDNA was obtained using First Strand cDNA Synthesis kit. SNP A2017G (rs3865014) was analyzed by Custom Real-Time SNP Array and GLCE expression levels were determined using Taq-Man-based Real-Time PCR (Applied Biosystems). Statistical analysis was carried out using a Statistika 9.0 software. Results: AA genotype carriers had a 2-fold increase in GLCE mRNA levels in tumors compared with control surrounding tissues (0.37 ± 0.77 versus 0.17 ± 0.16, respectively, p < 0.05). Oppositely, AG genotype carriers had a 1.5-fold decrease in GLCE mRNA levels in tumors compared with control surrounding tissues (0.39 ± 0.29 versus 0.58 ± 0.33, respectively, p < 0.05 ). However, in any case,the GLCE expression in both normal tissues and breast tumors was more active in AG genotype carriers than in AA carriers. It is known that LOH is often associated with molecular mechanisms of carcinogenesis, we studied this process for the same patients. According our results, LOH was detected in about 10% of cases (5/52 patients), among which G was lost in 3 patients and A was lost in 2 patients. Conclusion: The obtained data show a possible association between GLCE Ile597Val polymorphism and breast cancer, although the nature of the association remains ambiguous

GLCE rs3865014 (Val597Ile) polymorphism is associated with breast cancer susceptibility and triple-negative breast cancer in Siberian population

d-Glucuronyl C5-epimerase (GLCE) is one of key enzymes in heparan sulfate biosynthesis and possesses tumour-suppressor function in breast carcinogenesis. Here, we investigated a potential involvement of GLCE polymorphism(s) in breast cancer development in Siberian women population. Comprehensive analysis of SNP databases revealed GLCE rs3865014 (Val597Ile) missense polymorphism as the main significantly present in human populations. According the TaqMan-based SNP assay, allele distributions for the rs3865014 (A > G) were similar in healthy Siberian women (n = 136) and cancer patients (n = 129) (A0,73:G0,27) and intermediate between the European and Asian populations, while genotype distributions were different, with the increase of AG rate in breast cancer patients (OR = 1.76; 95% CI = 1.04–1.90; P(Y) = 0.035 χ2 = 4.44). Heterozygous AG genotype was associated with tumour size (OR = 3.67, P(Y) = 0.004), ER-negative tumours (OR = 3.25, P(Y) = 0.0028), triple-negative tumours (OR = 4.94, P(Y) = 0.015) but not menopausal status, PR and HER-2 status, local or distant metastasis. Homozygous GLCE genotypes (AA/GG) were more common for ER + PR + luminal A breast cancer (OR = 0.25, P(Y) = 0.031). Loss-of-heterozigosity was identified in 5 of 51 breast tumours and the loss of G allele was associated with the decreased GLCE expression. Epidemiologic data for the GLCE SNP in different racial/ethnic groups demonstrated high AG genotype rates as a risk factor not for breast cancer incidence but for poor prognosis of the disease. The obtained data suggest an involvement of GLCE rs3865014 in breast cancer development. Heterozygous AG genotype might be a risk factor for breast cancer susceptibility in Siberian women and is associated with aggressive ER-negative and triple-negative cancer subtypes

GLCE rs3865014 (Val597Ile) polymorphism is associated with breast cancer susceptibility and triple-negative breast cancer in Siberian population

d-Glucuronyl C5-epimerase (GLCE) is one of key enzymes in heparan sulfate biosynthesis and possesses tumour-suppressor function in breast carcinogenesis. Here, we investigated a potential involvement of GLCE polymorphism(s) in breast cancer development in Siberian women population. Comprehensive analysis of SNP databases revealed GLCE rs3865014 (Val597Ile) missense polymorphism as the main significantly present in human populations. According the TaqMan-based SNP assay, allele distributions for the rs3865014 (A > G) were similar in healthy Siberian women (n = 136) and cancer patients (n = 129) (A0,73:G0,27) and intermediate between the European and Asian populations, while genotype distributions were different, with the increase of AG rate in breast cancer patients (OR = 1.76; 95% CI = 1.04–1.90; P(Y) = 0.035 χ2 = 4.44). Heterozygous AG genotype was associated with tumour size (OR = 3.67, P(Y) = 0.004), ER-negative tumours (OR = 3.25, P(Y) = 0.0028), triple-negative tumours (OR = 4.94, P(Y) = 0.015) but not menopausal status, PR and HER-2 status, local or distant metastasis. Homozygous GLCE genotypes (AA/GG) were more common for ER + PR + luminal A breast cancer (OR = 0.25, P(Y) = 0.031). Loss-of-heterozigosity was identified in 5 of 51 breast tumours and the loss of G allele was associated with the decreased GLCE expression. Epidemiologic data for the GLCE SNP in different racial/ethnic groups demonstrated high AG genotype rates as a risk factor not for breast cancer incidence but for poor prognosis of the disease. The obtained data suggest an involvement of GLCE rs3865014 in breast cancer development. Heterozygous AG genotype might be a risk factor for breast cancer susceptibility in Siberian women and is associated with aggressive ER-negative and triple-negative cancer subtypes

Cell type specific, traceable gene silencing for functional gene analysis during vertebrate neural development.

Many genes have several, sometimes divergent functions during development. Therefore, timing of gene knockdown for functional analysis during development has to be done with precise temporal control, as loss of a gene's function at early stages prevents its analysis later in development. RNAi, in combination with the accessibility of chicken embryos, is an effective approach for temporally controlled analysis of gene function during neural development. Here, we describe novel plasmid vectors that contain cell type-specific promoters/enhancers to drive the expression of a fluorescent marker, followed directly by a miR30-RNAi transcript for gene silencing. These vectors allow for direct tracing of cells experiencing gene silencing by the bright fluorescence. The level of knockdown is sufficient to reproduce the expected pathfinding defects upon perturbation of genes with known axon guidance functions. Mixing different vectors prior to electroporation enables the simultaneous knockdown of multiple genes in independent regions of the spinal cord. This permits complex cellular and molecular interactions to be examined during development, in a fast and precise manner. The advancements of the in ovo RNAi technique that we describe will not only markedly enhance functional gene analysis in the chicken, but also could be adapted to other organisms in developmental studies