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      TUSC3: a novel tumour suppressor gene and its functional implications

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          Abstract

          The tumour suppressor candidate 3 ( TUSC3) gene is located on chromosome region 8p22 and encodes the 34 kD TUSC3 protein, which is a subunit of the oligosaccharyl transferase responsible for the N‐glycosylation of nascent proteins. Known to be related to autosomal recessive mental retardation for several years, TUSC3 has only recently been identified as a potential tumour suppressor gene. Based on the structure and function of TUSC3, specific mechanisms in various diseases have been investigated. Several studies have demonstrated that TUSC3 is an Mg 2+‐transporter involved in magnesium transport and homeostasis, which is important for learning and memory, embryonic development and testis maturation. Moreover, dysfunction or deletion of TUSC3 exerts its oncological effects as a modulator by inhibiting glycosylation efficiency and consequently inducing endoplasmic reticulum stress and malignant cell transformation. In this study, we summarize the advances in the studies of TUSC3 and comment on the potential roles of TUSC3 in diagnosis and treatment of TUSC3‐related diseases, especially cancer.

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          Most cited references50

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          Global variation in copy number in the human genome.

          Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.
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            A high-resolution survey of deletion polymorphism in the human genome.

            Recent work has shown that copy number polymorphism is an important class of genetic variation in human genomes. Here we report a new method that uses SNP genotype data from parent-offspring trios to identify polymorphic deletions. We applied this method to data from the International HapMap Project to produce the first high-resolution population surveys of deletion polymorphism. Approximately 100 of these deletions have been experimentally validated using comparative genome hybridization on tiling-resolution oligonucleotide microarrays. Our analysis identifies a total of 586 distinct regions that harbor deletion polymorphisms in one or more of the families. Notably, we estimate that typical individuals are hemizygous for roughly 30-50 deletions larger than 5 kb, totaling around 550-750 kb of euchromatic sequence across their genomes. The detected deletions span a total of 267 known and predicted genes. Overall, however, the deleted regions are relatively gene-poor, consistent with the action of purifying selection against deletions. Deletion polymorphisms may well have an important role in the genetics of complex traits; however, they are not directly observed in most current gene mapping studies. Our new method will permit the identification of deletion polymorphisms in high-density SNP surveys of trio or other family data.
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              Common deletion polymorphisms in the human genome.

              The locations and properties of common deletion variants in the human genome are largely unknown. We describe a systematic method for using dense SNP genotype data to discover deletions and its application to data from the International HapMap Consortium to characterize and catalogue segregating deletion variants across the human genome. We identified 541 deletion variants (94% novel) ranging from 1 kb to 745 kb in size; 278 of these variants were observed in multiple, unrelated individuals, 120 in the homozygous state. The coding exons of ten expressed genes were found to be commonly deleted, including multiple genes with roles in sex steroid metabolism, olfaction and drug response. These common deletion polymorphisms typically represent ancestral mutations that are in linkage disequilibrium with nearby SNPs, meaning that their association to disease can often be evaluated in the course of SNP-based whole-genome association studies.
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                Author and article information

                Contributors
                sunnydujuan@aliyun.com
                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                08 March 2017
                September 2017
                : 21
                : 9 ( doiID: 10.1111/jcmm.2017.21.issue-9 )
                : 1711-1718
                Affiliations
                [ 1 ] Department of Radiation Oncology Shandong Provincial Qianfoshan Hospital Shandong University Jinan China
                [ 2 ] Department of Cardiology Shandong Provincial Hospital affiliated to Shandong University Shandong University Jinan China
                [ 3 ] Medical Management Service Center of Shandong Provincial Health and Family Planning Commission Jinan China
                [ 4 ] Medical Research Center Shandong Provincial Qianfoshan Hospital Shandong University Jinan China
                [ 5 ] China Institute of Veterinary Drugs Control Beijing China
                Author notes
                [*] [* ] Correspondence to: Juan Du

                E‐mail: sunnydujuan@ 123456aliyun.com

                Article
                JCMM13128
                10.1111/jcmm.13128
                5571513
                28272772
                ac802679-17a5-4767-97ff-ea2d7536e5c7
                © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 March 2016
                : 13 January 2017
                Page count
                Figures: 3, Tables: 2, Pages: 8, Words: 5606
                Funding
                Funded by: Medical and Health Science and Technology Development Plan of Shandong Province
                Award ID: 2015WSB04012
                Award ID: 2015WS0213
                Funded by: Natural Science Foundation of Shandong Province
                Award ID: ZR2011HQ010
                Award ID: ZR2016HQ50
                Award ID: ZR2015HM077
                Funded by: National Natural Science Foundation of China
                Award ID: 30901712
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                jcmm13128
                September 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.8 mode:remove_FC converted:25.08.2017

                Molecular medicine
                tumour suppressor candidate 3,oligosaccharyl transferase,tumourgenesis,n‐glycosylation reaction

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