Investigating the molecular effects of the 16P11.2 copy number variant using an induced pluripotent stem cell model
Abstract/Contents
- Abstract
- The 16p11.2 copy number variant (CNV) locus is known to increase the risks of autism spectrum disorders (ASD), schizophrenia, and many other developmental problems in humans. However, it not understood as to how the CNVs at this locus, which occur as a heterozygous deletion or duplication of ~600 kbp in size, contribute to the development of these disorders. Previous studies have generated possible gene targets and pathways of interest for further investigation but due to the early onset nature of the phenotypes of the 16p11.2 CNVs, the studies were done using cell types that are not directly applicable (e.g. LCLs) or animal model systems. Here, we investigate the changes to gene expression and DNA methylation using a 16p11.2 CNV patient-derived induced pluripotent stem cell (iPSC) to induced neuron (iN) cell model system. This revealed global alterations to both gene expression and to DNA methylation patterns which further yielded new leads of genes potentially contributing to known patient phenotypes. Specifically, PCSK9 is identified as a possible contributing factor in the development of facial abnormalities in patients, along with also being involved with the reciprocal head circumference and body mass index (BMI) phenotypes seen in the deletion and duplication patients. Additionally, the protocadherin (PCDH) gene family is seen to have significantly altered methylation patterns in the CNV patient samples which could implicate these genes in the etiology of neuropsychiatric disorders.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Ward, Thomas Ray |
|---|---|
| Degree supervisor | Urban, Alexander E |
| Thesis advisor | Urban, Alexander E |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Sherlock, Gavin |
| Thesis advisor | Snyder, Michael |
| Degree committee member | Bassik, Michael |
| Degree committee member | Sherlock, Gavin |
| Degree committee member | Snyder, Michael |
| Associated with | Stanford University, Department of Genetics. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Thomas Ward. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Thomas Ray Ward
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...