Génétique moléculaire du glaucome primaire à angle ouvert au sein de la population québécoise

Authors: Faucher, Mathieu
Advisor: Raymond, Vincent
Abstract: The Québec population (~7 million residents) is constituted of approximately six million individuals that descended from an estimated genetic pool of 8500 founders. Utilizing the unique features of this population, this thesis is about the molecular genetics glaucoma, an insidious ocular disease that is a worldwide leading cause of blindness. To study the genetic factors involved in this disorder, we recruited families segregating primary open-angle glaucoma (POAG), and unrelated individuals also affected by glaucoma or ocular hypertension (OHT). Mutations of the TIGR/myocilin (MYOC) gene, until recently the only known genetic cause for juvenile and adult-onset POAG, have been screened in 18 families, representing 180 affected individuals, and 422 sporadic cases. Mutational analysis of this gene showed mutation prevalences of 22,2 and 3,8%, respectively, in families and unrelated patients. Genotype/phenotype correlations of some of the mutations found were established, revealing that the Gly367Arg and Lys423Glu mutations were the most severe. Characterization of allelic signatures surrounding the TIGR/MYOC gene allowed an estimation of the number of founders that may have disseminated the mutations found in the Québec population sample and an evaluation of the possible application of this technique to similar disorders. Eight families with enough individuals to undertake a preliminary linkage study were genotyped on six known glaucoma susceptibility regions. The genotyping of these families aimed the reduction of the genetic intervals of one or more of these known regions to eventually find a new glaucoma-causing gene. One family, representing a strong linkage potential to the GLC1B locus, was extended to have a higher number of affected individuals harboring the candidate disease haplotype linked to this region positioned at chromosome 2cen-q13. Although some interesting candidate genes were identified in this locus, the saturation of the chromosomal region with polymorphic markers revealed the absence of a common haplotype between all the affected individuals of this family. Additional recruiting of large families segregating POAG and the extension of some pedigrees already investigated will be necessary to the identification of new genetic factors closely involved in this common ocular pathology.
Document Type: Thèse de doctorat
Issue Date: 2003
Open Access Date: 11 April 2018
Permalink: http://hdl.handle.net/20.500.11794/17798
Grantor: Université Laval
Collection:Thèses et mémoires

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