Proteome-Wide Analysis of Single-Nucleotide Variations in the N-Glycosylation Sequon of Human Genes

Mazumder, Raja; Morampudi, Krishna Sudeep; Motwani, Mona; Vasudevan, Sona; Goldman, Radoslav
May 2012
PLoS ONE;May2012, Vol. 7 Issue 5, p1
Academic Journal
N-linked glycosylation is one of the most frequent post-translational modifications of proteins with a profound impact on their biological function. Besides other functions, N-linked glycosylation assists in protein folding, determines protein orientation at the cell surface, or protects proteins from proteases. The N-linked glycans attach to asparagines in the sequence context Asn-X-Ser/Thr, where X is any amino acid except proline. Any variation (e.g. non-synonymous single nucleotide polymorphism or mutation) that abolishes the N-glycosylation sequence motif will lead to the loss of a glycosylation site. On the other hand, variations causing a substitution that creates a new N-glycosylation sequence motif can result in the gain of glycosylation. Although the general importance of glycosylation is well known and acknowledged, the effect of variation on the actual glycoproteome of an organism is still mostly unknown. In this study, we focus on a comprehensive analysis of non-synonymous single nucleotide variations (nsSNV) that lead to either loss or gain of the Nglycosylation motif. We find that 1091 proteins have modified N-glycosylation sequons due to nsSNVs in the genome. Based on analysis of proteins that have a solved 3D structure at the site of variation, we find that 48% of the variations that lead to changes in glycosylation sites occur at the loop and bend regions of the proteins. Pathway and function enrichment analysis show that a significant number of proteins that gained or lost the glycosylation motif are involved in kinase activity, immune response, and blood coagulation. A structure-function analysis of a blood coagulation protein, antithrombin III and a protease, cathepsin D, showcases how a comprehensive study followed by structural analysis can help better understand the functional impact of the nsSNVs.


Related Articles

  • Association between Single Nucleotide Polymorphisms in the ADD3 Gene and Susceptibility to Biliary Atresia. Zeng, Shuaidan; Sun, Peng; Chen, Zimin; Mao, Jianxiong; Wang, Jianyao; Wang, Bin; Liu, Lei // PLoS ONE;Oct2014, Vol. 9 Issue 10, p1 

    Background and Objectives: Based on the results of previous studies, the ADD3 gene, located in the 10q24.2 region, may be a susceptibility gene of biliary atresia (BA). In this study, two single nucleotide polymorphisms (SNPs) in the ADD3 gene, rs17095355 C/T and rs10509906 G/C, were selected...

  • Insertion-deletions burden in copy number polymorphisms of the Tibetan population. Veerappa, Avinash M.; Vishweswaraiah, Sangeetha; Lingaiah, Kusuma; Murthy, N. Megha; Suresh, Raviraj V.; Belur, Keshava; Ramachandra, Nallur B.; Tejaswini; Patel, Niveditha B.; Supriya Gowda, P. K. // Indian Journal of Human Genetics;Apr-Jun2014, Vol. 20 Issue 2, p166 

    BACKGROUND: Many studies have been conducted to identify either insertions-deletions (inDels) or copy number variations (CNVs) in humans, but few studies have been conducted to identify both of these forms coexisting in the same region. AIMS AND OBJECTIVES: To map the functionally significant...

  • Deterministic identification of specific individuals from GWAS results. Ruichu Cai; Zhifeng Hao; Winslett, Marianne; Xiaokui Xiao; Yin Yang; Zhenjie Zhang; Shuigeng Zhou // Bioinformatics;Jun2015, Vol. 31 Issue 11, p1701 

    Motivation: Genome-wide association studies (GWASs) are commonly applied on human genomic data to understand the causal gene combinations statistically connected to certain diseases. Patients involved in these GWASs could be re-identified when the studies release statistical information on a...

  • Using SNPs to find my roots. Wingfield, Brenda // South African Journal of Science;Jan/Feb2014, Vol. 110 Issue 1/2, p11 

    The author discusses aspects of single-nucleotide polymorphism (SNP) genotyping in tracing people's ancestral roots. She articulates that understanding more about genetics and ones' own genomes through SNP linkage is important. She suggests that the availability of data on genotypes may compel a...

  • Some Observations for Discordant Sib Pair Design Using QTL-MAS 2010 Dataset. Karacaören, Burak // Kafkas Universitesi Veteriner Fakultesi Dergisi;2012, Vol. 18 Issue 5, p857 

    Association mapping seeks for markers at vicinity of genes affecting on complex traits. Family based association studies extensively used in human genetics for mapping genes. Discordant Sib Pair (DSP) design has advantages in controlling population stratification. The main aim of this paper was...

  • Co-regulated Transcripts Associated to Cooperating eSNPs Define Bi-fan Motifs in Human Gene Networks. Kreimer, Anat; Pe'er, Itsik // PLoS Genetics;Sep2014, Vol. 10 Issue 9, p1 

    Associations between the level of single transcripts and single corresponding genetic variants, expression single nucleotide polymorphisms (eSNPs), have been extensively studied and reported. However, most expression traits are complex, involving the cooperative action of multiple SNPs at...

  • Multiscale modeling of the causal functional roles of nsSNPs in a genome-wide association study: pplication to hypoxia. Li Xie; Clara Ng; Ali, Thahmina; Valencia, Raoul; Ferreira, Barbara L.; Xue, Vincent; Tanweer, Maliha; Dan Zhou; Haddad, Gabriel G.; Bourne, Philip E.; Lei Xie // BMC Genomics;2013, Vol. 14 Issue Suppl 3, p1 

    Background: It is a great challenge of modern biology to determine the functional roles of non-synonymous Single Nucleotide Polymorphisms (nsSNPs) on complex phenotypes. Statistical and machine learning techniques establish correlations between genotype and phenotype, but may fail to infer the...

  • Human genetics: Pleiotropic mutations. Stower, Hannah // Nature Reviews Genetics;Jan2012, Vol. 13 Issue 1, p5 

    The article presents a study in which authors use a large-scale analysis of single nucleotide polymorphisms (SNPs) and genes which are reported to be associated with common complex traits and diseases on abundant pleiotropy, in which each individual gene mutation has a role in multiple diseases.

  • A system for exact and approximate genetic linkage analysis of SNP data in large pedigrees. Silberstein, Mark; Weissbrod, Omer; Otten, Lars; Tzemach, Anna; Anisenia, Andrei; Shtark, Oren; Tuberg, Dvir; Galfrin, Eddie; Gannon, Irena; Shalata, Adel; Borochowitz, Zvi U.; Dechter, Rina; Thompson, Elizabeth; Geiger, Dan // Bioinformatics;Mar2013, Vol. 29 Issue 5, p669 

    A correction to the article "A system for exact and approximate genetic linkage analysis of SNP data in large pedigrees" that was published in the 2013 issue is presented.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics