FINDbase: a relational database recording frequencies of genetic defects leading to inherited disorders worldwide

Frequency of INherited Disorders database (FINDbase) () is a relational database, derived from the ETHNOS software, recording frequencies of causative mutations leading to inherited disorders worldwide. Database records include the population and ethnic group, the disorder name and the related gene, accompanied by links to any corresponding locus-specific mutation database, to the respective Online Mendelian Inheritance in Man entries and the mutation together with its frequency in that population. The initial information is derived from the published literature, locus-specific databases and genetic disease consortia. FINDbase offers a user-friendly query interface, providing instant access to the list and frequencies of the different mutations. Query outputs can be either in a table or graphical format, accompanied by reference(s) on the data source. Registered users from three different groups, namely administrator, national coordinator and curator, are responsible for database curation and/or data entry/correction online via a password-protected interface. Databaseaccess is free of charge and there are no registration requirements for data querying. FINDbase provides a simple, web-based system for population-based mutation data collection and retrieval and can serve not only as a valuable online tool for molecular genetic testing of inherited disorders but also as a non-profit model for sustainable database funding, in the form of a ‘database-journal’

Measurement of Phenyllactate, Phenylacetate, and Phenylpyruvate by Negative Ion Chemical Ionization-Gas Chromatography/Mass Spectrometry in Brain of Mouse Genetic Models of Phenylketonuria and Non-Phenylketonuria Hyperphenylalaninemia

Phenylketonuria (PKU) (OMIM 261600) is the first to stable PLA, which is labeled with a single deuterium and discriminated from endogenous PLA in the mass spectrometer on that basis. The method demonstrates that these metabolites are easily measured in normal mouse brain and are elevated moderately in HPA mice and greatly in PKU mice. However, their concentrations are not sufficient in PKU to be "toxic"; phenylalanine itself remains the chemical candidate causing impaired cognitive development

Étude démographique et généalogique de deux maladies héréditaires au Saguenay

La population du Saguenay est depuis longtemps reconnue pour l’ampleur des problèmes génétiques auxquels elle fait face. S’agissant en particulier de maladies récessives comme la tyrosinémie, l’ataxie de Friedreich (forme Charlevoix-Saguenay), le rachitisme ou l’agénésie du corps calleux, on a imputé les fortes incidences observées à divers facteurs comme les nombreux mariages consanguins, la stabilité de la population, un effet fondateur particulièrement accentué, un modèle particulier d’immigration, etc. Cependant, les analyses que nous avons commencé à réaliser à l’aide du fichier de population construit par SOREP obligent à réviser ces énoncés. La construction des généalogies par ordinateur et l’étude des comportements démographiques à l’aide de la reconstitution automatique des familles permettent en effet des analyses rétrospectives très approfondies et livrent des aperçus qui étaient hors de portée jusqu’à ce jour. L’enquête que nous rapportons ici revêt un caractère expérimental ; c'était la première fois que nous tentions une utilisation rigoureuse du fichier de population dans cette direction. Les résultats obtenus ont d’ores et déjà des retombées sur le conseil génétique et, en outre, ils modifient substantiellement notre perception de la dynamique démographique au Saguenay.The population of the Saguenay has long been known for the magnitude of the genetic problems it faces. In particular, since the problem is one of recessive illnesses such as tyrosinemia, Friedreich's ataxia (Charlevoix-Saguenay type), rickets or agenesis of corpus callosum, the strong observed effects have been ascribed to several factors such as the numerous mariages between blood relatives, the stability of the population, a particularly strong founder effect, a specific model of immigration, etc. However, the analysis we have begun to carry out with the aid of SOREP's population data base, forces us to revise these statements. The computer construction of genealogies and the study of demographic behaviour using automatic family reconstruction allow, indeed, for very thorough retrospective analyses, and deliver insights that, to this day, were out of reach. The survey on which we report is of an experimental nature; it was the first time we attempted a rigorous use of the population data base, for such purposes. The results obtained have already had an impact on underlying assumptions in the field of genetics, and moreover, they have substantially changed our perception of the demographic dynamics of the Saguenay.Hace tiempo que la población saguenayense es reputada por la envergadura de los problemas genéticos que enfrenta. Se trata particularmente de las enfermedades recesivas como la tirosinemia, la ataxia de Friedreich (tipo Charlevoix-Saguenay), el raquitismo o la agenesia del cuerpo calloso, cuya alta frecuencia se ha atribuido a diversos factores tales como el alto numero de uniones consanguíneas, la estabilidad de la población, un efecto "fundador" especialmente acentuado, un patrón particular de migración, etc. No obstante, los análisis que hemos comenzado a realizar gracias al archivo de población elaborado por SOREP (Sociedad de Investigaciones acerca de las Poblaciones), compelen a examinar de nuevo estos enunciados. La creación de genealogías por medio del computador y el estudio de los coiportamientos demográficos a través de la reconstitución automática de las familias, permiten elaborar análisis retrospectivos refinados que ofrecen una visión que antes estaba fuera de nuestro alcance. La investigación, de la cual damos cuenta en este articulo, es de carácter experimental; por primera ocasión intentamos el uso minucioso del archivo de población en este sentido. Los resultados obtenidos tienen ya su resonancia en la orientación que prodigan los genetistas, además de que modifican substancialmente nuestra percepción acerca de la dinámica demográfica del Saguenay