Persistence pays off for PCOS gene prospectors.
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ABSTRACT:
SUBMITTER: Strauss JF
PROVIDER: S-EPMC3387390 | biostudies-literature | 2012 Jul
REPOSITORIES: biostudies-literature
Publications
Persistence pays off for PCOS gene prospectors.
Strauss Jerome F JF McAllister Jan M JM Urbanek Margrit M
The Journal of clinical endocrinology and metabolism 20120701 7
Similar Datasets
Project description:BackgroundPolycystic ovary syndrome (PCOS) is a complex disease having both genetic and environmental components and candidate genes on obesity and insulin metabolism have been hypothesized to be involved in its etiology.ObjectiveWe examined the possible association of adiponectin and insulin receptor gene polymorphisms with PCOS.Materials and methodsA total of 186 women with PCOS using NIH criteria and 156 healthy women were recruited. Their samples were genotyped for the polymorphism in exon 17 and 8 of the insulin receptor gene or exon and intron 2 of the adiponectin gene.ResultsThe distributions of genotypes and alleles of both polymorphisms were not different in women with PCOS and controls. There was no significant differences on the anthropometric and hormonal profiles of various adiponectin and insulin receptor genes polymorphisms among both groups.ConclusionAdiponectin and insulin receptor gene polymorphisms are not associated with PCOS in a sample of Iranian population.
| S-EPMC3943219 | biostudies-literature
Project description:For a given carbon budget over several decades, different transformation rates for the energy system yield starkly different results. Here we consider a budget of 33 GtCO2 for the cumulative carbon dioxide emissions from the European electricity, heating, and transport sectors between 2020 and 2050, which represents Europe's contribution to the Paris Agreement. We have found that following an early and steady path in which emissions are strongly reduced in the first decade is more cost-effective than following a late and rapid path in which low initial reduction targets quickly deplete the carbon budget and require a sharp reduction later. We show that solar photovoltaic, onshore and offshore wind can become the cornerstone of a fully decarbonised energy system and that installation rates similar to historical maxima are required to achieve timely decarbonisation. Key to those results is a proper representation of existing balancing strategies through an open, hourly-resolved, networked model of the sector-coupled European energy system.
| S-EPMC7718908 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by hyperandrogenism and metabolic disorders. The excess androgens may be of both ovarian and adrenal origin. PCOS has a strong genetic component, and genome-wide association studies have identified several candidate genes, notably DENND1A, which encodes connecdenn 1, involved in trafficking of endosomes. DENND1A encodes two principal variants, V1 (1009 amino acids) and V2 (559 amino acids). The androgen-producing ovarian theca cells of PCOS women over-express V2. Knockdown of V2 in these cells reduces androgen production, and overexpression of V2 in normal theca cells confers upon them a PCOS phenotype of increased androgen synthesis. We report that human adrenal NCI-H295A cells express V1 and V2 mRNA and that the V2 isoform is produced by exonization of sequences in intron 20, which generates a unique exon 20A, encoding the C-terminus of V2. As in human theca cells from normal women, forced expression of V2 in NCI-H295A cells resulted in increased abundance of CYP17A1 and CYP11A1 mRNAs. We also found genetic variation in the intronic region 330 bp upstream from exon 20A, which could have the potential to drive the selective expression of V2. There was no clear association with these variants with PCOS when we analyzed genomc DNA from normal women and women with PCOS. Using minigene expression vectors in NCI-H295A cells, this variable region did not consistently favor splicing of the V2 transcript. These findings suggest increased V2 expression in PCOS theca cells is not the result of genomic sequence variation in intron 20.
| S-EPMC4983473 | biostudies-literature
Project description:AimTo identify pathogenic rare coding Mendelian/high-effect size variant(s) by whole-exome sequencing in familial polycystic ovary syndrome (PCOS) patients to elucidate PCOS-related pathways.MethodsTwenty women and their affected available relatives diagnosed with PCOS according to Rotterdam criteria were recruited. Whole-exome sequencing on germ-line DNA from 31 PCOS probands and their affected relatives was performed. Whole-exome sequencing data were further evaluated by pathway and chemogenomics analyses. In-slico analysis of candidate variants were done by VarCards for functional predictions and VarSite for impact on three-dimensional (3D) structures in the candidate proteins.ResultsTwo heterozygous rare FBN3 missense variants in three patients, and one FN1 missense variant in one patient from three different PCOS families were identified.ConclusionWe identified three novel FBN3 and FN1 variants for the first time in the literature and linked with PCOS. Further functional studies may identify causality of these newly discovered PCOS-related variants, and their role yet remains to be investigated. Our findings may improve our understanding of the biological pathways affected and identify new drug targets.
| S-EPMC9050819 | biostudies-literature
Project description:The National Lung Screening Trial (NLST) revealed that low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20.0%. In China, LDCT is very cheap and easy to access. As a result, LDCT screening is not limited to "high-risk" population defined by the NLST trial. The results of LDCT screening in China are also quite different from that in Western countries. LDCT detected lung cancer in a significant proportion of young, female and non-smokers in China. There is also a higher proportion of adenocarcinoma (ADC), a lower proportion of squamous cell carcinoma, and a higher proportion of early-stage 0/I disease among LDCT-detected lung cancer in China. The issue of overdiagnosis and overtreatment is discussed. Finally, we call the global attention to clarify the etiology of lung cancer in young female non-smokers.
| S-EPMC8182701 | biostudies-literature
Project description:Lung cancer is the leading cause of cancer-related death worldwide, and its early detection is critical to achieving a curative treatment and to reducing mortality. Low-dose computed tomography (LDCT) is a highly sensitive technique for detecting noninvasive small lung tumors in high-risk populations. We here analyze the current status of lung cancer screening (LCS) from a European point of view. With economic burden of health care in most European countries resting on the state, it is important to reduce costs of screening and improve its effectiveness. Current cost-effectiveness analyses on LCS have indicated a favorable economic profile. The most recently published analysis reported an incremental cost-effectiveness ratio (ICER) of €3,297 per 1 life-year gained adjusted for the quality of life (QALY) and €2,944 per life-year gained, demonstrating a 90% probability of ICER being below €15,000 and a 98.1% probability of being below €25,000. Different risk models have been used to identify the target population; among these, the PLCOM2012 in particular allows for the selection of the population to be screened with high sensitivity. Risk models should also be employed to define screening intervals, which can reduce the general number of LDCT scans after the baseline round. Future perspectives of screening in a European scenario are related to the will of the policy makers to implement policy on a large scale and to improve the effectiveness of a broad screening of smoking-related disease, including cardiovascular prevention, by measuring coronary calcium score on LDCT. The employment of artificial intelligence (AI) in imaging interpretation, the use of liquid biopsies for the characterization of CT-detected undetermined nodules, and less invasive, personalized surgical treatments, will improve the effectiveness of LCS.
| S-EPMC8182705 | biostudies-literature
Project description:BackgroundPolycystic ovary syndrome (PCOS) is a complex disease having both genetic and environmental components. Candidate genes with insulin metabolism have been hypothesized to be involved in the etiology of this syndrome. In the present study, we investigated the genetic association between polymorphisms in the insulin receptor (INSR) gene and PCOS.MethodsA total of 260 family trios were recruited and performed a family-based analysis to assess linkage and association between four single nucleotide polymorphisms (SNPs) (rs1799817, rs2059807, rs8108622 and rs10500204) of INSR gene and PCOS.ResultsUsing the transmission disequilibrium test (TDT), we failed to find that rs1799817 (p = 0.486), rs2059807 (p = 0.195), rs8108622 (p = 0.866) and rs10500204 (p = 1.0) were significantly overtransmitted to PCOS offspring from their parents.ConclusionNo significant evidence of association or linkage was found in the four tested markers, indicating that our family samples did not support susceptibility of the INSR gene to PCOS.
| S-EPMC3118173 | biostudies-literature
Project description: Not available
| S-EPMC4045401 | biostudies-literature
Project description:BACKGROUND: Gene clustering plays an important role in the organization of the bacterial chromosome and several mechanisms have been proposed to explain its extent. However, the controversies raised about the validity of each of these mechanisms remind us that the cause of this gene organization remains an open question. Models proposed to explain clustering did not take into account the function of the gene products nor the likely presence or absence of a given gene in a genome. However, genomes harbor two very different categories of genes: those genes present in a majority of organisms - persistent genes - and those present in very few organisms - rare genes. RESULTS: We show that two classes of genes are significantly clustered in bacterial genomes: the highly persistent and the rare genes. The clustering of rare genes is readily explained by the selfish operon theory. Yet, genes persistently present in bacterial genomes are also clustered and we try to understand why. We propose a model accounting specifically for such clustering, and show that indispensability in a genome with frequent gene deletion and insertion leads to the transient clustering of these genes. The model describes how clusters are created via the gene flux that continuously introduces new genes while deleting others. We then test if known selective processes, such as co-transcription, physical interaction or functional neighborhood, account for the stabilization of these clusters. CONCLUSION: We show that the strong selective pressure acting on the function of persistent genes, in a permanent state of flux of genes in bacterial genomes, maintaining their size fairly constant, that drives persistent genes clustering. A further selective stabilization process might contribute to maintaining the clustering.
| S-EPMC2234087 | biostudies-other
Project description:Polycystic ovary syndrome (PCOS), the most common endocrine disease among premenopausal women, is caused by both genes and environment. We and others previously reported association between single nucleotide polymorphisms (SNPs) in the DENND1A gene and PCOS. We therefore sequenced the DENND1A gene in white patients with PCOS to identify possible alterations that may be implicated in the PCOS pathogenesis. Patients were referred with PCOS and/or hirsutism between 1998 and 2011 (n = 261). PCOS was diagnosed according to the Rotterdam criteria (n = 165). Sequence analysis was performed in 10 patients with PCOS. Additional patients (n = 251) and healthy female controls (n = 248) were included for SNP genotyping. Patients underwent clinical examination including Ferriman-Gallwey score (FG-score), biochemical analyses and transvaginal ultrasound. Mutation analysis was carried out by bidirectional sequencing. SNP genotyping was tested by allelic discrimination in real-time PCR in the additional patients and controls. Sequencing of the DENND1A gene identified eight SNPs; seven were not known to be associated with any diseases. One missense SNP was detected (rs189947178, A/C), potentially altering the structural conformation of the DENND1A protein. SNP genotyping of rs189947178 showed significantly more carriers among patients with PCOS and moderate hirsutism compared to controls. However, due to small sample size and lack of multiple regression analysis supporting an association between rs189947178 and FG-score or PCOS diagnosis, this could be a false positive finding. In conclusion, sequence analysis of the DENND1A gene of patients with PCOS did not identify alterations that alone could be responsible for the PCOS pathogenesis, but a missense SNP (rs189947178) was identified in one patient and significantly more carriers of rs189947178 were found among patients with PCOS and moderate hirsutism vs. controls. Additional studies with independent cohort are needed to confirm this due to the small sample size of this study.
| S-EPMC3785455 | biostudies-literature