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We explore the possibility that defects in genes associated with the response and repair of DNA double strand breaks predispose oral potentially malignant disorders (OPMD) to undergo malignant transformation to oral squamous cell carcinoma (OSCC). Defects in the homologous recombination/Fanconi anemia (HR/FA), but not in the non-homologous end joining, causes the DNA repair pathway to appear to be consistent with features of familial conditions that are predisposed to OSCC (FA, Bloom's syndrome, Ataxia Telangiectasia); this is true for OSCC that occurs in young patients, sometimes with little/no exposure to classical risk factors. Even in Dyskeratosis Congenita, a disorder of the telomerase complex that is also predisposed to OSCC, attempts at maintaining telomere length involve a pathway with shared HR genes. Defects in the HR/FA pathway therefore appear to be pivotal in conditions that are predisposed to OSCC. There is also some evidence that abnormalities in the HR/FA pathway are associated with malignant transformation of sporadic cases OPMD and OSCC. We provide data showing overexpression of HR/FA genes in a cell-cycle-dependent manner in a series of OPMD-derived immortal keratinocyte cell lines compared to their mortal counterparts. The observations in this study argue strongly for an important role of the HA/FA DNA repair pathway in the development of OSCC. [ABSTRACT FROM AUTHOR]

Microsatellite DNA variation was examined in rainbow trout (Oncorhynchus mykiss) populations from throughout British Columbia, Canada, to address the roles of historical isolation, postglacial dispersal, and contemporary geomorphology in structuring genetic variation and differentiation. We detected signatures of historical isolation and postglacial recolonization in the form of 'interior' and 'coastal' population groupings, a decline in genetic variation as distance increased from putative glacial refugia, and different extents of isolation-by-distance in different regions. Rainbow trout populations were structured genetically into major regions and into smaller watersheds and then into drainages. Within drainages, high levels of dispersal and gene flow were inferred between geographically proximate and contiguous lakes. Elevation, stream branching points (nodes), fluvial distance, migration barriers, and stream and lake order influenced genetic diversity within, and differentiation among, populations. Habitat characteristics, particularly lake surface area and perimeter, were poor predictors of genetic variation. Although founder events and postglacial dispersal influenced broadscale patterns of genetic diversity in rainbow trout, our results suggest that contemporary factors can strongly modulate historical patterns. Resume: L'etude de la variation de l'ADN des microsatellites chez des populations de truites arc-en-ciel (Oncorhynchus mykiss) dans l'ensemble de la Colombie-Britannique nous permet de determiner les roles de l'isolement passe, de la dispersion postglaciaire et de la geomorphologie contemporaine sur la structuration et la differenciation de la variation gene- tique. Nous decelons des signatures de l'isolement passe et de la recolonisation postglaciaire sous forme de groupements de populations ≪ interieures ≫ et ≪ cotieres ≫, de declin de la variation genetique en fonction de la distance croissante des refuges glaciaires putatifs et d'isolements par la distance d'importances diverses dans les differentes regions. Les populations de truites arc-en-ciel se structurent genetiquement en regions majeures, puis en reseaux hydrographiques plus petits et finalement en bassins de drainage. Dans les bassins, on concluon un haut niveau de dispersion et de flux genique entre les lacs contigus et rapproches geographiquement. L'altitude, les points (n[??]uds) de branchement des cours d'eau, la distance fluviale, les barrieres a la migration et l'ordre des cours d'eau et des lacs influencent la diversite genetique au sein des populations et la differenciation entre les populations. Les caracteristiques de l'habitat, particulierement la superficie et le perimetre des lacs, sont de mauvaises variables predictives de la variation genetique. Bien que les evenements du fondateur et la dispersion postglaciaire influencent les patrons de diversite genetique a grande echelle chez la truite arc-en-ciel, nos resultats indiquent que les facteurs actuels peuvent fortement moduler les patrons du passe. [Traduit par la Redaction], Introduction Understanding the influences of environmental and geographical factors, whether they be historical or contemporary in nature, on the distribution of genetic variation in populations is an important aspect of [...]