Novel Sequence Variants in exon11.3 of BRCA1 gene in Breast and Ovarian Cancer Patients of Madhya Pradesh (India)

Study was carried out onpatients (N=100) of different age group and menopausal condition, diagnosed with breast (n=60) and ovarian (n=30) cancer of Gwalior region, Madhya Pradesh (India). Blood sample collection, DNA isolation, DNA polymerization and sequencing of exon11.3 region of BRCA1 gene was carried out with standard protocol. Sequences were analyzed for mutation through various computation methods and comparative analysis with reference sequence of BRCA1 gene. Multiple sequence alignment highlighted the conserved pattern and mutation in patients sequences. 5 critical mutations were identified comprised of one frameshift (c.1378delA, 1382delA) and 4 missense (1334A>T, 1335A>T, 1336A>T; c.1386A>G, 1369A>T; c.1394T>C, 1397A>T, 1398G>T; c.1582C>A) type. Each mutation was observedto be 1.11% in population. Deleterious frameshift mutation was found to be homozygous and out of 4 missense mutations, 3 were heterozygousand one washomozygous type. Predicted pathogenic nature of mutations are due to change in splicing signal, change in chemical nature of DNA binding domain of BRCA1 protein. Entries of these mutations are not found in BIC, therefore considered as novel one.