Evaluation and Identification of Damaged Single Nucleotide Polymorphisms in COL1A1 Gene Involved in Osteoporosis

Overview

Journal Arch Med Sci

Specialty General Medicine

Date 2013 Nov 26

PMID 24273577

Citations 2

Authors

Tariq Ahmad Masoodi

Mohammed A Alsaif

Sulaiman A Al Shammari

Adel A Alhamdan

Affiliations

Soon will be listed here.

Abstract

Introduction: Single-nucleotide polymorphisms (SNPs) are biomarkers for exploring the genetic basis of many complex human diseases. The prediction of SNPs is promising in modern genetic analysis but it is still a great challenge to identify the functional SNPs in a disease-related gene. The computational approach has overcome this challenge and an increase in the successful rate of genetic association studies and reduced cost of genotyping have been achieved. The objective of this study is to identify deleterious non-synonymous SNPs (nsSNPs) associated with the COL1A1 gene.

Material And Methods: The SNPs were retrieved from the Single Nucleotide Polymorphism Database (dbSNP). Using I-Mutant, protein stability change was calculated. The potentially functional nsSNPs and their effect on proteins were predicted by PolyPhen and SIFT respectively. FASTSNP was used for estimation of risk score.

Results: Our analysis revealed 247 SNPs as non-synonymous, out of which 5 nsSNPs were found to be least stable by I-Mutant 2.0 with a DDG value of > -1.0. Four nsSNPs, namely rs17853657, rs17857117, rs57377812 and rs1059454, showed a highly deleterious tolerance index score of 0.00 with a change in their physicochemical properties by the SIFT server. Seven nsSNPs, namely rs1059454, rs8179178, rs17853657, rs17857117, rs72656340, rs72656344 and rs72656351, were found to be probably damaging with a PSIC score difference between 2.0 and 3.5 by the PolyPhen server. Three nsSNPs, namely rs1059454, rs17853657 and rs17857117, were found to be highly polymorphic with a risk score of 3-4 with a possible effect of non-conservative change and splicing regulation by FASTSNP.

Conclusions: Three nsSNPs, namely rs1059454, rs17853657 and rs17857117, are potential functional polymorphisms that are likely to have a functional impact on the COL1A1 gene.

Citing Articles

Comprehensive Computational Analysis of Protein Phenotype Changes Due to Plausible Deleterious Variants of Human SPTLC1 Gene.

Sadaf T, John P, Bhatti A Int J Mol Cell Med. 2020; 8(1):67-84.

PMID: 32195206 PMC: 7073263. DOI: 10.22088/IJMCM.BUMS.8.1.67.

Association of insulin-like growth factor I gene polymorphisms with the risk of osteoporosis in a Chinese population.

Fan Y, Zhang S, Liang F, Zhou Y Int J Clin Exp Pathol. 2020; 10(8):8443-8451.

PMID: 31966696 PMC: 6965436.

References

Sunyaev S, Ramensky V, Bork P . Towards a structural basis of human non-synonymous single nucleotide polymorphisms. Trends Genet. 2000; 16(5):198-200. DOI: 10.1016/s0168-9525(00)01988-0. View

Sherry S, Ward M, Kholodov M, Baker J, Phan L, Smigielski E . dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2000; 29(1):308-11. PMC: 29783. DOI: 10.1093/nar/29.1.308. View

Thomas R, McConnell R, Whittacker J, Kirkpatrick P, Bradley J, Sandford R . Identification of mutations in the repeated part of the autosomal dominant polycystic kidney disease type 1 gene, PKD1, by long-range PCR. Am J Hum Genet. 1999; 65(1):39-49. PMC: 1378073. DOI: 10.1086/302460. View

Yoshida A, Huang I, Ikawa M . Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals. Proc Natl Acad Sci U S A. 1984; 81(1):258-61. PMC: 344651. DOI: 10.1073/pnas.81.1.258. View

Stover D, Verrelli B . Comparative vertebrate evolutionary analyses of type I collagen: potential of COL1a1 gene structure and intron variation for common bone-related diseases. Mol Biol Evol. 2010; 28(1):533-42. DOI: 10.1093/molbev/msq221. View

George Priya Doss C, Sethumadhavan R . Investigation on the role of nsSNPs in HNPCC genes--a bioinformatics approach. J Biomed Sci. 2009; 16:42. PMC: 2682794. DOI: 10.1186/1423-0127-16-42. View

Ramensky V, Bork P, Sunyaev S . Human non-synonymous SNPs: server and survey. Nucleic Acids Res. 2002; 30(17):3894-900. PMC: 137415. DOI: 10.1093/nar/gkf493. View

Dryja T, McGee T, Hahn L, Cowley G, Olsson J, Reichel E . Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa. N Engl J Med. 1990; 323(19):1302-7. DOI: 10.1056/NEJM199011083231903. View

Altschul S, Madden T, Schaffer A, Zhang J, Zhang Z, Miller W . Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997; 25(17):3389-402. PMC: 146917. DOI: 10.1093/nar/25.17.3389. View

10.

Barroso I, Gurnell M, Crowley V, Agostini M, Schwabe J, Soos M . Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature. 2000; 402(6764):880-3. DOI: 10.1038/47254. View

11.

Xi T, Jones I, Mohrenweiser H . Many amino acid substitution variants identified in DNA repair genes during human population screenings are predicted to impact protein function. Genomics. 2004; 83(6):970-9. DOI: 10.1016/j.ygeno.2003.12.016. View

12.

Johnson M, Houck J, Chen C . Screening for deleterious nonsynonymous single-nucleotide polymorphisms in genes involved in steroid hormone metabolism and response. Cancer Epidemiol Biomarkers Prev. 2005; 14(5):1326-9. DOI: 10.1158/1055-9965.EPI-04-0815. View

13.

Capriotti E, Fariselli P, Casadio R . I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure. Nucleic Acids Res. 2005; 33(Web Server issue):W306-10. PMC: 1160136. DOI: 10.1093/nar/gki375. View

14.

Ng P, Henikoff S . SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003; 31(13):3812-4. PMC: 168916. DOI: 10.1093/nar/gkg509. View

15.

Rajasekaran R, Sudandiradoss C, George Priya Doss C, Sethumadhavan R . Identification and in silico analysis of functional SNPs of the BRCA1 gene. Genomics. 2007; 90(4):447-52. DOI: 10.1016/j.ygeno.2007.07.004. View

16.

Aronow W . Osteoporosis, osteopenia, and atherosclerotic vascular disease. Arch Med Sci. 2012; 7(1):21-6. PMC: 3258682. DOI: 10.5114/aoms.2011.20599. View

17.

Dolan P, Torgerson D . The cost of treating osteoporotic fractures in the United Kingdom female population. Osteoporos Int. 1999; 8(6):611-7. DOI: 10.1007/s001980050107. View

18.

Sjolander K, Karplus K, Brown M, Hughey R, KROGH A, Mian I . Dirichlet mixtures: a method for improved detection of weak but significant protein sequence homology. Comput Appl Biosci. 1996; 12(4):327-45. DOI: 10.1093/bioinformatics/12.4.327. View

19.

Smith E, Boyd J, Frank G, Takahashi H, Cohen R, Specker B . Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med. 1994; 331(16):1056-61. DOI: 10.1056/NEJM199410203311604. View

20.

Sadat-Ali M, Alelq A . Osteoporosis among male Saudi Arabs: a pilot study. Ann Saudi Med. 2006; 26(6):450-4. PMC: 6074334. DOI: 10.5144/0256-4947.2006.450. View