First Advisor

Deborah Duffield

Term of Graduation

2011

Date of Publication

1-1-2011

Document Type

Thesis

Degree Name

Master of Science (M.S.) in Biology

Department

Biology

Language

English

Subjects

Asymmetrical organ development, Atrioventricular septal defects, Heterotaxy, Congenital heart disease -- Molecular diagnosis, Heart -- Diseases -- Genetic aspects, Heart septum -- Abnormalities

DOI

10.15760/etd.410

Physical Description

1 online resource (x, 62 pages)

Abstract

Heterotaxy refers to the abnormal arrangement of internal organs in relation to each other. Model organism studies have shown that functions of more than eighty genes are required for normal asymmetric left-right organ development. CRELD1 has been shown to be necessary for proper heart development and mutations in CRELD1 are known to increase risk of cardiac atrioventricular septal defects (AVSD). AVSD is the most common form of heart defect associated with heterotaxy, and we have previously shown that some individuals heterotaxy-related AVSD have mutations in CRELD1.

Therefore, we propose to examine the CRELD1 gene in a large sample of patients with heterotaxy syndrome. Our goal was to determine if mutations in CRELD1 are associated with other manifestations of heterotaxy or if they only coincide with AVSD. To achieve this aim, a sample size of 126 patients with heterotaxy collected by Dr. Belmont, Baylor college of Medicine, Texas, with approximately 66% of the heterotaxy population with different types of heart defects, were used for this study. Ten exons, promoter regions, and regulatory elements in the introns of CRELD1 gene were sequenced and analyzed.

In this study three different heterozygous missense mutations in CRELD1 were identified in three unrelated individuals. These three individuals were diagnosed with different forms of heart defects in addition to AVSD. All three mutations were identified in highly conserved regions of CRELD1 possibly altering the CRELD1 properties. This demonstrates that mutations in CRELD1 may increase the susceptibility of AVSD in heterotaxy population. This information can help us to find factors effecting disease susceptibility in heterotaxy patients since the heart defects are a complex trait with incomplete penetrance.

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Persistent Identifier

http://archives.pdx.edu/ds/psu/7367

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