Title: Effect of single amino acid mutations on C-terminal domain of breast cancer susceptible protein 1

Authors: Satish Kumar; Lingaraja Jena; Maheswata Sahoo; Kanchan Mohod; Sangeeta Daf; Ashok K. Varma

Addresses: Bioinformatics Centre and Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram (Wardha) 442 102, Maharashtra, India ' Bioinformatics Centre and Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram (Wardha) 442 102, Maharashtra, India ' Bioinformatics Centre and Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram (Wardha) 442 102, Maharashtra, India ' Bioinformatics Centre and Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram (Wardha) 442 102, Maharashtra, India ' Obstetrics & Gynaecology Datta Meghe Institute of Medical Sciences, Mother Care Hospital, Umred Road, Nagpur 440017, Maharashtra, India ' Varma Lab, Advanced Centre for Treatment, Research and Education in Cancer, Khargar 410210, Navi Mumbai, India

Abstract: The most commonly diagnosed cancer in women is the breast cancer. Around 5-10% of breast cancer cases are hereditary, mainly due to the mutation in the breast cancer susceptible Breast Cancer 1 (BRCA1) and Breast Cancer 2 (BRCA2) tumour-suppressor genes. More than hundreds mutations are documented in BRCA1 C-terminal region (BRCT), mainly associated with repairing DNA damage and cell cycle control. In this study, we employed different mutation analysis system such as sorting intolerant from tolerant, MutPred, PON-P2, Meta-SNP, etc., to predict the pathological effects of 95 distinct miss sense mutation on BRCT domain. Out of which, 37 mutations were predicted to be deleterious by all mutation analysis systems affecting the protein stability and its normal function leading to causing cancer. The computational approach for finding out the impact of mutation on BRCA protein may provide a way in early detection and therapy in breast cancer patients.

Keywords: Bioinformatics; BRCA1; BRCT; breast cancer; mutation analysis; mutation.

DOI: 10.1504/IJBRA.2019.103783

International Journal of Bioinformatics Research and Applications, 2019 Vol.15 No.4, pp.305 - 323

Received: 20 Oct 2016
Accepted: 02 Sep 2017
Published online: 29 Nov 2019 *

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