Author ORCID Identifier

https://orcid.org/ 0000-0002-1152-9968

Document Type

Dissertation

Date of Award

2022

Degree Name

Doctor of Philosophy (PhD)

Department

Basic Biomedical Science

First Advisor

Erik A Ehli

Abstract

Twins have long been of interest for illuminating genetic and environmental influences on human traits and diseases. These explorations have been accelerated by the substantial amount of information collected from twins and their families participating in twin registers around the world. In this dissertation, I review what is known and what remains unknown about the biology and genetics of twins and the underlying twinning process. To elucidate additional genetic factors of the twinning process, I employed pedigree-based analysis to identify genetic regions shared among distantly related mothers of dizygotic twins. The shared regions may potentially contain rare genetic variants with substantial structural and functional implication in multiple ovulation events leading to the development of twins. With samples obtained from global twin-family populations, I demonstrated that Australian, Dutch, and Midwestern American populations are genetically similar and can be reasonably combined for joint genetic analysis. Aggregation of genetic and phenotypic data from twin registers provides insight into the role of genetics of human complex traits, such as birthweight. Meta-analysis of eight twin cohorts indicated that the same genetic variants underly birthweight in twins and non-twins and that future genome-wide studies might benefit from including data from large twin registers. Population-based association studies are also sensitive to variation in genetic ancestry. Employing two analytical approaches, I evaluated genetic ancestry estimates between twins and family members and across genotyping platforms. The findings from this work have important implication in data aggregation practices in twin and family-based studies. Overall, important scientific and medical findings involve global populations of twins and their relatives.

Subject Categories

Genetics | Molecular Genetics

Keywords

Twins, Molecular Genetics

Number of Pages

308

Publisher

University of South Dakota

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