STUDY ON IMPLICATIONS OF COPY NUMBER VARIATIONS (CNVs) IN HUMAN POPULATION
Objective: To investigate the role and implications of copy number variations (CNVs) in different diseases found in the human population using various computational tools and databases.
Methods: Five different diseases were taken into consideration namely Autism, Type-II Diabetes, Rheumatoid Arthritis, Breast Cancer, and Psoriasis. To validate the CNV's associated with various human diseases different tools and databases were used such as CNV annotator, DECIPHER, Database of Genomic Variants (DGV), CNVD, CNV Workshop, CNV Web store. Finally, the results were analysed to identify the extent of CNVs association in selected diseases.
Results: Among all the selected diseases, the maximum numbers of CNVâ€™s were found in the case of breast cancer which in total 3851 at chromosome number one. Among all the selected diseases, minimum numbers of CNVâ€™s were found in the case of psoriasis, and a significant amount of CNVs are present in all the selected diseases.
Conclusion: CNVs constitutes a substantial fraction of total genetic variability and it has the importance in modulating human diseases. This study has shown a significant presence of CNVs in all the selected diseases. Hence it can be concluded that CNVs can be major causing factors in many other life threatening diseases as well and a specific study designed to identify these variations can open a new dimension in the development of novel therapy for those diseases.
2. Zhao M, Zhao Z. CN Vannotator: A comprehensive annotation server for copy number variation in the human genome. Plos One 2013;8. https://doi.org/10.1371/journal.pone.0080170
3. Hollox EJ, Barber JCK, Brookes AJ, Armour JAL. Defensins and the dynamic Genome: what we can learn from structural vari-ation at human chromosome band 8p23.1. Genome Res 2016;18:1686-97.
4. Shishido E, Aleksic B, Ozaki N. Copy number variations in the pathogenesis of autism spectrum disorder. Psychiatry Clin Neurosci 2013;68:456-64.
5. Jonah DH, Logan RB, Maynard R, Jennifer EA, Brian CB, David JR, et al. VISA-vector integration site analysis server: a web-based server to rapidly identify retroviral integration sites from next-generation sequencing. BMC Bioinf 2015;16:212.
6. Almal S, Padh H. Frequency distribution of autoimmunity associated fcgr3b gene copy number in indian population. Im-munogenetics 2016;1:2.
7. Willer CJ, Speliotes EK, Loos RJ. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009;41:25â€“34.
8. Masson LA, Talseth-Palmer BA, Evans EJ, Grice MD, Hannan NG, Scott RJ. Expanding the genetics basis of copy number var-iation in familial breast cancer. Hered Cancer Clin Practice 2014;12:15-25.
9. Hollox EJ, Huffmeier U, Zeeuwen PLJM, Raquel P, Lascorz J, Olthuis DR, et al. Psoriasis is associated with increased beta-defensins genomic copy number. Nat Genet 2008;40:23-5.
10. Bae JS, Cheong SH, Kim JH, Park BL, Kim HJ, Park JT, et al. The genetic effect of copy number variations on the risk of type 2 diabetes in a korean population. Plos One 2016;22:e19091.
11. Zilina O, Koltsina M, Raid R, Kurg A, Tonisson N, Salumets A. Somatic mosaicism for copy-neutral loss of heterozygosity and DNA copy number variations in the human genome. BMC Genomics 2015;16:703.
12. Qiu F, Xu Y, Li K, Li Z, Liu Y, DuanMu H, et al. CNVD: text mining-based copy number variation in disease database. Hum Mutat 2012;33:2375-81.
13. Helen VF, Shola MR, Bevan AP, Stephen C, Manuel C, Diana R, et al. Decipher: a database of chromosomal imbalance and phenotype in humans using ensembl resources. Am J Hum Genet 2016;84:524-33.
14. MacDonald JR, Robert Z, Ryan KCY, Lars F, Stephen WS. The database of genomic variants: a curated collection of structur-al variation in the human genome. Nucleic Acids Res 2014;42:986-92.
15. Marshall CR, Scherer SW. Detection and characterization of copy number variation in autism spectrum disorder. Methods Mol Biol 2012;838:115-35.
16. Duffin KC, Woodcock J, Krueger GG. Genetic variations associ-ated with psoriasis and psoriatic arthritis found by genome-wide association. Dermatol Ther 2010;23:101-13.
17. Chen JY, Wang CM, Chang SW, Cheng CH, Wu YJ, Lin JC, et al. Association of FCGR3A and FCGR3B copy number variations with systemic lupus erythematosus and rheumatoid arthritis in taiwanese patients. Arthritis Rheumatol 2014;66:3113-21.
18. Prabhanjan M, Suresh RV, Murthy MN, Ramachandra NB. Type 2 diabetes mellitus disease risk genes identified by genome wide copy number variation scan in normal populations. Dia-betes Res Clin Pract 2016;113:160-70.
19. Walker LC, Wiggins GAR, Pearson JF. The role of constitutional copy number variants in breast cancer. Microarray 2015;4:407-23.
20. Shlien A, Malkin D. Copy number variations and cancer. Ge-nome Med 2009;1:62.