|
General Comment |
HIghly expressed in uterus and hypothalamus (BIoGPS).
NCBI Summary:
This gene encodes an transmembrane protein that functions as an ATP-dependent transporter of monoamines, such as dopamine, norepinephrine, serotonin, and histamine. This protein transports amine neurotransmitters into synaptic vesicles. Polymorphisms in this gene may be associated with schizophrenia, bipolar disorder, and other neurological/psychiatric ailments. [provided by RefSeq, Jun 2018]
|
|
Comment |
Genomewide discovery and classification of candidate ovarian fertility genes in the mouse. Gallardo TD et al. Female infertility syndromes are among the most prevalent chronic health disorders in women, but their genetic basis remains unknown because of uncertainty regarding the number and identity of ovarian factors controlling the assembly, preservation, and maturation of ovarian follicles. To systematically discover ovarian fertility genes en masse, we employed a mouse model (Foxo3) in which follicles are assembled normally but then undergo synchronous activation. We developed a microarray-based approach for the systematic discovery of tissue-specific genes and, by applying it to Foxo3 ovaries and other samples, defined a surprisingly large set of ovarian factors (n = 348, approximately 1% of the mouse genome). This set included the vast majority of known ovarian factors, 44% of which when mutated produce female sterility phenotypes, but most were novel. Comparative profiling of other tissues, including microdissected oocytes and somatic cells, revealed distinct gene classes and provided new insights into oogenesis and ovarian function, demonstrating the utility of our approach for tissue-specific gene discovery. This study will thus facilitate comprehensive analyses of follicle development, ovarian function, and female infertility. This gene is expressed in granulosa cells but not oocyte in developing and adult ovaries.
|
|
Mutations |
2 mutations
Species: mouse
Mutation name: None
type: naturally occurring
fertility: fertile
Comment: An Integrative Genomic Analysis of the Superior Fecundity Phenotype in QSi5 Mice. Wei J et al. Laboratory inbred mouse models are a valuable resource to identify quantitative trait loci (QTL) for complex reproductive performance traits. Advances in mouse genomics and high density single nucleotide polymorphism mapping has enabled genome-wide association studies to identify genes linked with specific phenotypes. Gene expression profiles of reproductive tissues also provide potentially useful information for identifying genes that play an important role. We have developed a highly fecund inbred strain, QSi5, with accompanying genotyping for comparative analysis of reproductive performance. Here we analyzed the QSi5 phenotype using a comparative analysis with fecundity data derived from 22 inbred strains of mice from the Mouse Phenome Project, and integration with published expression data from mouse ovary development. Using a haplotype association approach, 400 fecundity-associated regions (FDR<0.05) with 499 underlying genes were identified. The most significant associations were located on Chromosomes 14, 8, and 6, and the genes underlying these regions were extracted. When these genes were analyzed for expression in an ovarian development profile (GSE6916) several distinctive co-expression patterns across each developmental stage were identified. The genetic analysis also refined 21 fecundity associated intervals on Chromosomes 1, 6, 9, 13, and 17 that overlapped with previously reported reproductive performance QTL. The combined use of phenotypic and in silico data with an integrative genomic analysis provides a powerful tool for elucidating the molecular mechanisms underlying fecundity. TABLE 4.
Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Genetic variations in the 3'-untranslated region of SLC18A2 are associated with serum FSH concentration in polycystic ovary syndrome patients and regulate gene expression in vitro. Li Q et al. (2016) Are genetic variations at the human solute carrier family 18 member A2 (SLC18A2) locus associated with the etiology of polycystic ovary syndrome (PCOS) and/or with follicle stimulating hormone (FSH) levels and insulin secretion in PCOS? We found two common genetic variants in the 3'-untranslated region of SLC18A2 (rs363282 and rs363238) that are associated with serum FSH concentration in the PCOS group. SLC18A2 is a vesicular monoamine transporter that is essential in dopamine regulation. Dopamine can negatively regulate FSH and insulin secretion through the D2 receptor. This study was a cross-sectional examination in women with PCOS (n = 319) and controls (n = 220) from China. The PCOS patients were diagnosed based on the criteria of the Androgen Excess Society, including clinical and/or biochemical signs of hyperandrogenemia plus oligoamenorrhea or polycystic ovaries. Controls had regular menstrual cycles and no hyperandrogenism or other endocrine disorders related to PCOS. Tag single nucleotide polymorphisms (SNPs) were selected based on resequencing data in 48 PCOS patients and linkage disequilibrium analysis. Allele frequencies for variants (rs363282 and rs363238) were examined in PCOS cases and controls along with their relationship to quantitative traits. The samples were further divided into two subgroups for association analysis: AA + AG group and GG group (rs363282), CC + AC group and AA group (rs363238). The functional effects of SLC18A2 variants were measured by luciferase assay. The gene expression of SLC18A2 was compared with the NCBI's Gene Expression Omnibus datasets. Two common genetic variants in the 3'-untranslated region (rs363282 and rs363238) are associated with serum FSH in the PCOS group (P= 0.005 and P= 0.001, respectively), while no associations were found in controls. Functional studies showed that minor alleles of the two variants (rs363282-G and rs363238-A) had significantly lower luciferase activities than rs363282-A (P= 0.009) and rs363238-C (P = 0.009). Results were not validated in another independent cohort, though we provided functional evidence of the two SNPs. Because of limited condition, more specific parameters, including ovarian follicle count and anti-Müllerian hormone were not included and relationship between SLC18A2 and these parameters cannot be evaluated. We found a novel association between two genetic variants in SLC18A2 and FSH levels in PCOS patients. These findings might indicate a novel regulatory mechanism in follicular development and maturation in PCOS. This work was supported by the National Natural Science Foundation of China (grant numbers 81571501 and 81270747), National Basic Research Program of China (grant number 2015CB943300). No competing interests declared.//////////////////
|