Role of EMG1 in Bowen-Conradi syndrome and in ribosome biogenesis
| dc.contributor.author | Armistead, D. Joy | |
| dc.contributor.examiningcommittee | Duckworth, Mary Lynn (Physiology) Rockman-Greenberg, Cheryl (Pediatrics and Child Health) Ding, Hao (Biochemistry and Medical Genetics) Rommens, Johanna (University of Toronto) | en_US |
| dc.contributor.supervisor | Triggs-Raine, Barbara (Biochemistry and Medical Genetics) | en_US |
| dc.date.accessioned | 2014-04-07T14:53:14Z | |
| dc.date.available | 2014-04-07T14:53:14Z | |
| dc.date.issued | 2009-06 | en_US |
| dc.date.issued | 2013 | en_US |
| dc.degree.discipline | Biochemistry and Medical Genetics | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | Bowen-Conradi syndrome is a lethal autosomal recessive disorder affecting Hutterite infants, characterized by severe growth and psychomotor retardation, and leading to death at an average age of thirteen months. Linkage analysis and sequencing identified an A>G mutation in EMG1 as the probable cause of the disease. This gene is implicated in ribosome biogenesis, and the mutation results in an unstable EMG1 protein. The reduction in available EMG1 causes a transient delay in processing of the ribosomal small subunit 18S rRNA, leading to cell cycle delay at G2/M and a subsequent reduction in cell proliferation rates in patient lymphoblasts. A mouse model of Bowen-Conradi syndrome also displayed severe developmental delay, with prominent effects in the cranial central nervous system. Embryos died prematurely during development, probably due to decreased proliferation rates accompanied by apoptosis. These results shed light on the etiology of Bowen-Conradi syndrome, and open the door for development of treatments. | en_US |
| dc.description.note | May 2014 | en_US |
| dc.identifier.citation | Joy Armistead, Sunita Khatkar, Britta Meyer, Brian Mark, Nehal Patel, Peter Koetter, Gail Coghlan, Ryan E.Lamont, Shuangbo Liu, Jill Wiechert, Peter A. Cattini, Yvonne Myal, Klaus Wrogemann, Cheryl Greenberg, Karl-Dieter Entian, Teresa Zelinski, Barbara Triggs-Raine. Mutation of a gene essential for ribosome biogenesis, EMG1, causes Bowen-Conradi Syndrome. American Journal of Human Genetics. 2009 Jun;84(6):728-39. | en_US |
| dc.identifier.citation | Joy Armistead and Barbara Triggs-Raine. EMG1 harbouring the Bowen-Conradi syndrome D86G substitution localizes normally but has reduced stability. In Ribosomes: Molecular structure, role in biological functions and implications for genetic diseases, Zhou Lin and Wang Liu, eds. Nova Science Publishers, New York. 2013. | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/23413 | |
| dc.language.iso | eng | en_US |
| dc.publisher | The American Society of Human Genetics | en_US |
| dc.publisher | Nova Science Publishers | en_US |
| dc.rights | open access | en_US |
| dc.subject | Bowen-Conradi syndrome | en_US |
| dc.subject | EMG1 | en_US |
| dc.subject | ribosome | en_US |
| dc.subject | Hutterite | en_US |
| dc.subject | mouse model | en_US |
| dc.title | Role of EMG1 in Bowen-Conradi syndrome and in ribosome biogenesis | en_US |
| dc.type | doctoral thesis | en_US |
| local.subject.manitoba | yes | en_US |