|
General Comment |
Small Ubiquitin-like Modifier (or SUMO) proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function. SUMOylation is a post-translational modification involved in various cellular processes, such as nuclear-cytosolic transport, transcriptional regulation, apoptosis, protein stability, response to stress, and progression through the cell cycle.////////////////////Molecular features of human ubiquitin-like
SUMO genes and their encoded proteins. [Su HL et al. (2003) The SUMO (small ubiquitin-like modifier) protein and ubiquitin have similar 3-D structure. Sumolyzation and ubiquitination exhibit similar biological processes for post-translational modification. However, unlike ubiquitination, which targets proteins for degradation, sumolyzation participates in a number of cellular processes such as nuclear transport, transcriptional regulation, apoptosis and protein stability. The human genome contains three SUMO-1/2/3 functional genes, as well as eight SUMO-1 pseudogenes and 23 SUMO-2 pseudogenes, but no SUMO-3 pseudogenes. The protein-coding sequence of the SUMO-1 gene is interrupted by four introns, while those of SUMO-2 and SUMO-3 genes are interrupted by three introns. Human SUMO-1 protein exhibits 44% sequence identity with SUMO-2 and SUMO-3 proteins, while SUMO-2 and SUMO-3 proteins share 86% sequence identity. Phylogenetic analyses indicate that the SUMO-3 gene was derived from the SUMO-2 gene. SUMO-1 mRNA appears to be most abundant in human epithelial HeLa, kidney 293 and neuronal NT2 cells, while the SUMO-3 mRNA seems to be much less abundant than SUMO-2 mRNA, especially in HeLa and 293 cells. Many cellular proteins of high molecular weights were covalently modified by SUMO-1/2/3 proteins. However, some free form of SUMO-2/3 proteins was also detected. Most SUMO-1/2/3 proteins were shown to be localized on nuclear membrane, nuclear bodies and cytoplasm, respectively.//////////////////
|
|
Mutations |
2 mutations
Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. Shi Y et al. Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 ?10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.
Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Cross-Ethnic Meta-analysis of Genetic Variants for Polycystic Ovary Syndrome. Louwers YV 2013 et al.
ContextGenome Wide Association Studies (GWAS) have revealed new susceptibility loci for Chinese patients with Polycystic Ovary Syndrome (PCOS). Since ethnic background adds to phenotypic diversities in PCOS, it seems plausible that genetic variants associated with PCOS act differently in various ethnic populations.ObjectiveWe studied cross-ethnic effects of Chinese PCOS loci, i.e., LHCGR, THADA, DENND1A, FSHR, c9orf3, YAP1, RAB5B/SUOX, HMGA2, TOX3, INSR, SUMO1P1, in patients of Northern European descent.DesignGenetic association study conducted at an University Medical Center.PatientsAssociation was studied in 703 Dutch PCOS patients and 2164 Dutch controls. To assess the cross-effect, we performed a meta-analysis of the Dutch data combined with results of previously published studies in PCOS patients from China (n=2254) and the United States (n=2618) (US). Adjusted for multiple testing, a p-value < 3.110(-3) was considered statistically significant.ResultsMeta-analysis of the Chinese, US and Dutch data resulted 12 significant variants mapping to the YAP1 (p-value=1.010(-9)), RAB5B/SUOX (p-value=3.810(-11)), LHCGR (p-value=4.110(-4)), THADA (p-value=2.210(-4) and p-value=1.310(-3)), DENND1A (p-value=2.310(-3) and p-value=2.510(-3)), FSHR (p-value=3.810(-5) and p-value=3.610(-4)), c9orf3 (p-value=2.010(-6) and p-value=9.210(-6)), SUMO1P1 (p-value=2.310(-3)) loci with ORs ranging from 1.19-1.45 and 0.79-0.87.ConclusionsOverall, we observed for 12 out of 17 genetic variants mapping to the Chinese PCOS loci similar effect size and identical direction in PCOS patients from Northern European ancestry, indicating a common genetic risk profile for PCOS across populations. Therefore, it is expected, that large GWAS in PCOS patients from Northern European ancestry will partly identify similar loci as the GWAS in Chinese PCOS patients.
/////////////////////////
|