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Using genome-scale bioinformatics platforms to investigate the role of single nucleotide polymorphisms in the BRCA1 gene in key molecular pathways of disease / REBECCA WALL

Swansea University Author: REBECCA WALL

Abstract

Single nucleotide polymorphisms (SNPs) are often associated with conferring risk for disease, and are associated with many complex diseases such as breast and ovarian cancer. The BRCA1 gene is known to carry mutations that can predispose an individual to such diseases. Currently, the clinical signif...

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Published: Swansea 2022
Institution: Swansea University
Degree level: Master of Research
Degree name: MSc by Research
Supervisor: Mullins, Jonathan
URI: https://cronfa.swan.ac.uk/Record/cronfa60377
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first_indexed 2022-07-04T12:06:42Z
last_indexed 2023-01-13T19:20:27Z
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spelling 2022-07-04T13:13:48.9236637 v2 60377 2022-07-04 Using genome-scale bioinformatics platforms to investigate the role of single nucleotide polymorphisms in the BRCA1 gene in key molecular pathways of disease a55bd26f2989727f4bac9d4334dac6ea REBECCA WALL REBECCA WALL true false 2022-07-04 Single nucleotide polymorphisms (SNPs) are often associated with conferring risk for disease, and are associated with many complex diseases such as breast and ovarian cancer. The BRCA1 gene is known to carry mutations that can predispose an individual to such diseases. Currently, the clinical significance of most SNPs remains unknown due to the lack of successful and reliable classification tools, leading to the possibility that many pathogenic SNPs are not considered during genetic screening. In order to investigate the role of SNPs within crucial pathways and the structural effects of SNPs, a database and data collection pipeline was constructed that sourced information from Reactome, ClinVar, and UniProt. A second pipeline was created that allowed for the modelling of variant proteins. Through querying the database, direct pathway associations with BRCA1 were identified. Protein variant modelling revealed a novel approach to structural analysis of SNPs, allowing for differences in heuristic structural functions to be measured between pathogenic and benign variants. Of particular interest, the heuristic functions that showed the most significant differences were the van der Waals contacts and strict hydrogen bonds. Identification of SNPs within genes linked to complex diseases, such as BRCA1, can inform better targets of genetic screening and potentially provide new drug targets. E-Thesis Swansea 27 5 2022 2022-05-27 COLLEGE NANME COLLEGE CODE Swansea University Mullins, Jonathan Master of Research MSc by Research 2022-07-04T13:13:48.9236637 2022-07-04T13:04:17.5634242 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine REBECCA WALL 1 60377__24442__23ab6d6fa7b64c108a244f894d26883f.pdf Wall_Rebecca_MSc_Research_Thesis_Final_Cronfa.pdf 2022-07-04T13:09:10.6673327 Output 1715694 application/pdf E-Thesis – open access true Copyright: The author, Rebecca Wall, 2022. true eng
title Using genome-scale bioinformatics platforms to investigate the role of single nucleotide polymorphisms in the BRCA1 gene in key molecular pathways of disease
spellingShingle Using genome-scale bioinformatics platforms to investigate the role of single nucleotide polymorphisms in the BRCA1 gene in key molecular pathways of disease
REBECCA WALL
title_short Using genome-scale bioinformatics platforms to investigate the role of single nucleotide polymorphisms in the BRCA1 gene in key molecular pathways of disease
title_full Using genome-scale bioinformatics platforms to investigate the role of single nucleotide polymorphisms in the BRCA1 gene in key molecular pathways of disease
title_fullStr Using genome-scale bioinformatics platforms to investigate the role of single nucleotide polymorphisms in the BRCA1 gene in key molecular pathways of disease
title_full_unstemmed Using genome-scale bioinformatics platforms to investigate the role of single nucleotide polymorphisms in the BRCA1 gene in key molecular pathways of disease
title_sort Using genome-scale bioinformatics platforms to investigate the role of single nucleotide polymorphisms in the BRCA1 gene in key molecular pathways of disease
author_id_str_mv a55bd26f2989727f4bac9d4334dac6ea
author_id_fullname_str_mv a55bd26f2989727f4bac9d4334dac6ea_***_REBECCA WALL
author REBECCA WALL
author2 REBECCA WALL
format E-Thesis
publishDate 2022
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description Single nucleotide polymorphisms (SNPs) are often associated with conferring risk for disease, and are associated with many complex diseases such as breast and ovarian cancer. The BRCA1 gene is known to carry mutations that can predispose an individual to such diseases. Currently, the clinical significance of most SNPs remains unknown due to the lack of successful and reliable classification tools, leading to the possibility that many pathogenic SNPs are not considered during genetic screening. In order to investigate the role of SNPs within crucial pathways and the structural effects of SNPs, a database and data collection pipeline was constructed that sourced information from Reactome, ClinVar, and UniProt. A second pipeline was created that allowed for the modelling of variant proteins. Through querying the database, direct pathway associations with BRCA1 were identified. Protein variant modelling revealed a novel approach to structural analysis of SNPs, allowing for differences in heuristic structural functions to be measured between pathogenic and benign variants. Of particular interest, the heuristic functions that showed the most significant differences were the van der Waals contacts and strict hydrogen bonds. Identification of SNPs within genes linked to complex diseases, such as BRCA1, can inform better targets of genetic screening and potentially provide new drug targets.
published_date 2022-05-27T04:18:26Z
_version_ 1763754226693963776
score 11.01297

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