Copies of author's previously published articles inserted. / Errata pasted onto front end-paper. / Bibliography: leaves 111-139. / xii, 139, [34] leaves, [25] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Defines the origin of ring extra structurally abnormal chromosomes (ESACs), relates the genetic content of different ring ESACs derived from the same chromosome with the patient's pheuotype, generates probes for diagnostic use and refines the critical region of Wolf-Hirschhorn syndrome. / Thesis (Ph.D.)--University of Adelaide, Dept. of Paediatrics, 1998

Thesis (Ph. D.)--University of Adelaide, Dept. of Paediatrics, 1998. / Copies of author's previously published articles inserted. Errata pasted onto front end-paper. Includes bibliographical references (leaves 111-139).

Thesis advisor: Laura Anne Lowery / Wolf Hirschhorn Syndrome (WHS) is a neurodevelopmental disorder characterized by craniofacial malformations, heart and skeletal defects, intellectual disability as well as seizure disorders. While this disorder is thought to arise from a deletion of a region on the short arm of chromosome 4, which includes the four genes WHSC1, WHSC2, LETM1 and TACC3, the mechanism by which loss of these genes results in WHS is not understood. Given that these genes have been linked to cell migration and that affected tissues include those derived from the neural crest, we propose that WHS results from a defect in neural crest cell migration. Here, we show that WHSC1, WHSC2, TACC3 and LETM1 are all expressed along the neural tube and developing neural folds during Xenopus embryonic development. These genes are additionally enriched in the pharyngeal arches, which are migrating neural crest cells. The knockdown of these WHS-related genes leads to variable defects in craniofacial and cartilage morphology. Moreover, the loss of WHS gene expression causes defects in forebrain and midbrain development. This implicates these four genes in the WHS phenotype. Further analysis of both WHSC1 and TACC3 function show that their individual knockdown causes defective neural crest cell migration both in vivo and in vitro. This supports the notion that the WHS phenotype is a result of erroneous neural crest cell motility. Our analysis shows that the WHS related genes; WHSC1, WHSC2, LETM1 and TACC3, play a role in the WHS phenotype of craniofacial malformation, skeletal abnormality, and microcephaly. Further analysis of these genes will determine the combinatorial effects of their knockdown on neural crest cell migration during embryonic development to further elucidate the mechanism through which WHS develops. / Thesis (BS) — Boston College, 2018. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Departmental Honors. / Discipline: Biology.