Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form
D-Scholarship @ Pitt Banner and Links to Homepage

Analysis of Somatic Mutations in the Brain Regions of Alzheimer Disease Cases Using Whole-genome Sequencing

Acharya, Vibha (2024) Analysis of Somatic Mutations in the Brain Regions of Alzheimer Disease Cases Using Whole-genome Sequencing. Master's Thesis, University of Pittsburgh. (Unpublished)

[img] PDF
Restricted to University of Pittsburgh users only until 2 January 2026.
Download (2MB) | Request a Copy
[img] Microsoft Excel (Supplementary Material)
Supplemental Material
Restricted to University of Pittsburgh users only until 2 January 2026.
Download (116kB) | Request a Copy

Abstract

Alzheimer’s disease (AD) is the seventh leading cause of death worldwide and the most prevalent dementia . Age is the most significant risk factor for AD. With the shift in global demographics from younger to older adults, the age-related diseases such as AD will pose a huge public health burden. Genetic studies using human populations have identified the risk and protective genes, and cell and animal models have illustrated the pathways and the underlying biology of the AD. However, these findings do not offer a complete understanding of genetic susceptibility to AD. Somatic mutations, the well-known causative risk factors of neoplasm, have also been implicated in non-cancerous diseases and these somatic mutations could contribute to liability of AD. We explored the burden of somatic mutations in four brain regions (hippocampus, entorhinal cortex, cingulate gyrus and cerebellum) of 6 AD cases along with their corresponding blood as the control. We found that somatic mutations were mostly present in intergenic and intronic regions with the greatest number of mutations present in an immune related gene, LILBR1 and a synaptic vesicle related gene , SYN3. We observed several pathogenic mutations in the MMP9, CALCR1, and NPAP1. Gene set-enrichment analysis showed that these genes are involved in response to amyloid beta . Our study shows that pathogenic mutations in the AD brain could increase the risk of developing AD. Future studies in cell models might help in understanding the precise role of these pathogenic somatic variants in AD.

Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Acharya, Vibhavia16@pitt.eduvia160000-0001-6598-0052
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorKamboh, MIkamboh@pitt.eduKAMBOH
Committee MemberFeingold, Efeingold@pitt.eduFEINGOLD
Committee MemberFan, Kang-Hsienfrank.fan@pitt.edufrank.fan
Committee MemberKofler, Juliakoflerjk@upmc.edu
Date: 2 January 2024
Date Type: Publication
Defense Date: 15 November 2023
Approval Date: 2 January 2024
Submission Date: 6 December 2023
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 80
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Human Genetics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Somatic mutation, Alzheimer's disease, brain regions, MMP9, CALCR
Date Deposited: 02 Jan 2024 15:11
Last Modified: 02 Jan 2024 15:11
URI: http://d-scholarship.pitt.edu/id/eprint/45557

Metrics

Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item