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From syndromes to normal variation: a candidate gene study of interorbital distances

Wesoly, Samantha (2017) From syndromes to normal variation: a candidate gene study of interorbital distances. Master's Thesis, University of Pittsburgh. (Unpublished)

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Hypertelorism and telecanthus are clinical phenotypes associated with many genetic syndromes. To date, research is limited regarding whether disease-causing genes are related to normal craniofacial development in unaffected individuals. The aim of this study is to determine whether common genetic variation in forty selected genes implicated in hypertelorism/telecanthus-related syndromes contribute to normal variation of intercanthal and outer-canthal distances of the orbits. Hypertelorism/telecanthus-related genes were selected based on significant prevalence of the phenotype in the described genetic syndrome. Using the 3D Facial Norms (TDFN) Repository, genomic and anthropometric data were utilized to test genetic association for common variants in two phenotypes: intercanthal and outer-canthal distances. Suggestive SNPs with evidence of association were annotated for relevant gene function related to craniofacial development. For the intercanthal distance measurement, one statistically significant SNP (p<4.05x10-6) in LINC00482 and two suggestive SNPs (p<10-4), one in HMGCS2 and another within 200kB of FAM58A, were observed. For the outer-canthal distance measurement, five suggestive SNPs (p<10-4) were observed near ADAMTS18, GLI3, ACTG1, MEGF11, and SPECC1L. We hypothesize that identified SNPs have regulatory effects on the expression of these genes and contribute to interorbital distances in unaffected individuals.
Identifying genetic determinants of craniofacial development in the normal population is important for the understanding of mechanisms underlying craniofacial dysmorphology. In addition, understanding the mechanisms that contribute to the transition from normal variation to a disease state in a population is important to public health because most genetic diseases exist on a spectrum. With better understanding the unaffected side of the spectrum allows us to better identify the disease side of the spectrum, allowing for better diagnosis and treatment for individuals with craniofacial anomalies. This study attempts to identify these risk loci and hypothesize what impact these loci might have on craniofacial development.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Wesoly, Samanthaslw77@pitt.eduslw77
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWeinberg,
Committee MemberShaffer,
Committee MemberLeslie,
Committee MemberGrubs,
Date: 29 June 2017
Date Type: Publication
Defense Date: 14 April 2017
Approval Date: 29 June 2017
Submission Date: 3 April 2017
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 56
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Genetic Counseling
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: hypertelorism, telecanthus, craniofacial development, candidate gene study
Date Deposited: 29 Jun 2017 23:35
Last Modified: 29 Jun 2017 23:35


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