Three‐dimensional structural location and molecular functional effects of missense SNPs in the T cell receptor Vβ domain

Zheng Wang; John Moult

doi:10.1002/prot.10522

journal article Oct 01, 2003

Three‐dimensional structural location and molecular functional effects of missense SNPs in the T cell receptor Vβ domain

Zheng Wang

John Moult

Proteins: Structure, Function, and Bioinformatics Vol. 53 No. 3 pp. 748-757 · Wiley

View at Publisher Save 10.1002/prot.10522

Abstract

AbstractThe mechanisms by which human single nucleotide polymorphisms (SNPs) influence susceptibility to disease are not yet well understood. In a previous study, we developed a structure‐based model that may be used to identify which missense SNPs are neutral and which are deleterious to protein function and so potentially involved in disease (Wang and Moult, Hum Mutat 2001;263–270). The model has now been applied to a set of 54 missense cSNPs in the 46 functional T‐cell receptor Vβ‐genes. Most of these missense cSNPs are found to be neutral, but 10 are identified as likely deleterious to protein function. Only one was previously associated with disease. We suggest that the others may be disease related but that redundancy in the T‐cell response prevents any simple, monogenic effect. Therefore, these SNPs are the most likely contributors to complex, polygenic disease traits. It has been noted that there is a surprisingly high (74%) fraction of nonsynonymous SNPs in these genes. Contrary to expectation, the analysis shows that these are not associated with an unusually high fraction of deleterious SNPs, nor do they significantly contribute to a larger range of antigen recognition or a reduced superantigen‐binding repertoire. Proteins 2003. © 2003 Wiley‐Liss, Inc.

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References

56

[1]

10.1002/humu.22

[2]

10.1002/(sici)1098-1004(200001)15:1<45::aid-humu10>3.0.co;2-t

[3]

10.1126/science.291.5507.1224

[4]

SNP association studies in Alzheimer's disease highlight problems for complex disease analysis

T Emahazion

Trends in Genetics 10.1016/s0168-9525(01)02342-3

[5]

Prediction of deleterious human alleles

S. Sunyaev

Human Molecular Genetics 10.1093/hmg/10.6.591

[6]

Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation11Edited by F. Cohen

Daniel Chasman, R.Mark Adams

Journal of Molecular Biology 10.1006/jmbi.2001.4510

[7]

10.1101/gr.176601

[8]

Characterization of disease-associated single amino acid polymorphisms in terms of sequence and structure properties 1 1Edited by J. Thornton

Carles Ferrer-Costa, Modesto Orozco, Xavier de la Cruz

Journal of Molecular Biology 10.1006/jmbi.2001.5255

[9]

Human non-synonymous SNPs: server and survey

V. Ramensky

Nucleic Acids Research 10.1093/nar/gkf493

[10]

10.1086/321297

[11]

10.1126/science.3317824

[12]

10.1038/334395a0

[13]

10.1016/s0952-7915(01)00298-9

[14]

10.1016/0198-8859(96)00083-3

[15]

The Complete 685-Kilobase DNA Sequence of the Human β T Cell Receptor Locus

Lee Rowen, Ben F. Koop, Leroy Hood

Science 10.1126/science.272.5269.1755

[16]

10.1016/s0065-2776(08)60534-9

[17]

10.1016/s0092-8674(00)80338-4

[18]

10.1038/365642a0

[19]

10.1002/art.1780360717

[20]

10.1126/science.7701320

[21]

10.1126/science.274.5285.209

[22]

10.1093/emboj/16.14.4205

[23]

10.1093/emboj/17.1.10

[24]

10.1038/384134a0

[25]

10.1016/s0960-9822(98)70160-5

[26]

10.1016/s0958-1669(98)80004-9

[27]

10.1016/s1074-7613(00)80546-4

[28]

10.1126/science.286.5446.1913

[29]

10.1038/384188a0

[30]

10.1016/s1074-7613(00)80646-9

[31]

10.1146/annurev.immunol.17.1.435

[32]

10.1038/312040a0

[33]

10.1046/j.1365-2958.1997.3381696.x

[34]

10.1093/emboj/18.1.9

[35]

Characterization of single-nucleotide polymorphisms in coding regions of human genes

Michele Cargill, David Altshuler, James Ireland et al.

Nature Genetics 10.1038/10290

[36]

Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis

Marc K. Halushka, Jian-Bing Fan, Kimberly Bentley et al.

Nature Genetics 10.1038/10297

[37]

The Sequence of the Human Genome

J. Craig Venter, Mark D. Adams, Eugene W. Myers et al.

Science 10.1126/science.1058040

[38]

Basic local alignment search tool

Stephen F. Altschul, Warren Gish, Webb Miller et al.

Journal of Molecular Biology 10.1016/s0022-2836(05)80360-2

[39]

10.1016/s0076-6879(96)66024-8

[40]

10.1016/s0958-1669(99)00037-3

[41]

Bayesian statistical analysis of protein side‐chain rotamer preferences

Roland L. Dunbrack, Fred E. Cohen

Protein Science 10.1002/pro.5560060807

[42]

Canonical structures for the hypervariable regions of immunoglobulins

Cyrus Chothia, Arthur M. Lesk

Journal of Molecular Biology 10.1016/0022-2836(87)90412-8

[43]

Conformations of immunoglobulin hypervariable regions

Cyrus Chothia, Arthur M. Lesk, Anna Tramontano et al.

Nature 10.1038/342877a0

[44]

10.1006/jmbi.1999.3358

[45]

A Mathematical Theory of Communication

C. E. Shannon

Bell System Technical Journal 10.1002/j.1538-7305.1948.tb01338.x

[46]

Classical Electrostatics in Biology and Chemistry

Barry Honig, Anthony Nicholls

Science 10.1126/science.7761829

[47]

An Evolutionary Trace Method Defines Binding Surfaces Common to Protein Families

Olivier Lichtarge, Henry R. Bourne, Fred E. Cohen

Journal of Molecular Biology 10.1006/jmbi.1996.0167

[48]

10.1016/s0161-5890(99)00032-2

[49]

10.1007/bf00166831

[50]

10.1016/s0952-7915(01)00300-4

Showing 50 of 56 references

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Details

Published: Oct 01, 2003
Vol/Issue: 53(3)
Pages: 748-757
License: View

Authors

Qinghai University

Research Institute for Bioscience and Biotechnology

Cite This Article

Zheng Wang, John Moult (2003). Three‐dimensional structural location and molecular functional effects of missense SNPs in the T cell receptor Vβ domain. Proteins: Structure, Function, and Bioinformatics, 53(3), 748-757. https://doi.org/10.1002/prot.10522

Three‐dimensional structural location and molecular functional effects of missense SNPs in the T cell receptor Vβ domain

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