Exploring the camouflaged and non-coding genome: analysing difficult genomic regions in human disease genetics

The main objective of this thesis is to highlight the importance of investigating camouflaged regions, specifically segmental duplications, and non-coding regions, in the human genome. These regions, often overlooked due to their complexity, hold immense potential for uncovering novel insights into disease genetics. In pursuit of this objective, this thesis first focused on the study of camouflaged and non-coding regions in the context of schizophrenia. Schizophrenia is a complex psychiatric disorder specific to humans characterized by a combination of altered cognitive function, distorted perception, and disrupted social behaviour. Understanding the genetic underpinnings of schizophrenia is crucial for advancing our knowledge of its aetiology and developing more effective diagnostic and therapeutic approaches. Through comprehensive genomic analyses, novel insights were gained, which identified a novel duplication in a locus affecting a dopamine receptor implicated in neurotransmission. Additionally, small deletions in constrained non-coding regulatory regions were implicated in schizophrenia for the first time. Moreover, this thesis characterizes a long non-coding RNA (lncRNA) originating from the segmentally duplicated Pregnancy-Specific Glycoprotein locus. The lncRNA was expressed exclusively in oligodendrocytes, implicating it in the regulation of myelination processes in the brain. This lncRNA is human-specific, further emphasizing the biological relevance of camouflaged and non-coding regions in the context of human evolution. Throughout this thesis, a human-specific perspective was adopted, recognizing the unique genomic features that shape our species. By expanding our knowledge of difficult genomic regions, such as camouflaged and non-coding regions, this thesis aims to close the gap in the missing heritability problem and to gain a comprehensive understanding of the genetic architecture underlying complex disorders and uniquely human traits like schizophrenia.

Grantor dc:publisher

University College Cork

Year dc:date.issued

2023

Author dc:creator

• Becerra Rodríguez , Maria de los Ángeles

Advisors dc:contributor.advisor

• Moore, Thomas F.
• Baranov, Pavel V.

• Camouflaged
• Genome
• Non-coding
• Schizophrenia
• Human
• PSG8-AS1
• Copy number variants

Statement dc:rights

• © 2023, Maria de los Ángeles Becerra Rodríguez.

Licence dc:rights.uri

• https://creativecommons.org/licenses/by-nc-nd/4.0/

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10468/14996

OAI identifier oai:identifier

oai:cora.ucc.ie:10468/14996