Browsing by Author "MUHAMMAD SAQIB NAWAZ"

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    Insilico analysis of SNP pathogenesis in THYROGLOBULIN (TG) gene and its role in onset and propagation of thyroid cancer
    (UMT Lahore, 2022-04-28) MUHAMMAD SAQIB NAWAZ
    Thyroid cancer is a thyroid gland related disease and mainly arise due to hormonal imbalance of thyroid glands. Its symptoms include a lump or swelling in neck, voice change, difficulty in swallowing and a continuous cough. Thyroid cancer can be differentiated (Papillary, Follicular and Medullary) or undifferentiated (Anaplastic) in nature. Papillary cancer is the most common among the types almost 80%. Other thyroid related disorders like congenital hypothyroidism, thyroid dyshormogenesis and goitre are also seen along with thyroid tumor. Protein of Thyroglobulin (TG) gene act as a precursor of thyroid hormones (T3 and T4) and store Iodine which is required in biosynthesis of thyroid hormones. Aim of my study is to study all the pathogenic, functional and missense SNPs mutations in this gene which can trigger or have a role in thyroid cancer. The non-synonymous SNPs (nsSNPs) dataset of respected gene retrieved from gnomAD is the first step in step-wise functional characterization including sequence homology based analysis, machine learning based analysis, evolutionary conservation study and sequence based stability analysis. Four mutations (R169C, R2242H, G2319S and R2336Q) were filtered out after functional analysis were termed as highly unstable and conserved and selected for further analysis. Structure based stability analysis of wild-type and mutant 3D protein models reveal a clear difference in Gibbs free energies between wild type and mutant protein models. Possible disease association pathway was proposed by studying literature and assessing Pathway analysis databases which revealed that thyroglobulin was involved in biosynthesis of thyroid hormones and when normal functioning of this protein disturbs it causes thyroid related disorders and may possibly be involved in cancer development.