Abstracts
Résumé
Les méthodes modernes d’analyse du génome ont permis d’aborder des questions posées de longue date telles que les bases moléculaires des anomalies chromosomiques de structure ou la diathèse (prédisposition) aux aneuploïdies. L’architecture du génome révélée par le séquençage permet d’expliquer la récurrence de microremaniements par échange homologue non-allélique entre des répétitions segmentaires formées au cours de l’évolution des primates. Cette particularité structurale du génome a conduit à l’individualisation d’une nouvelle classe de maladies génétiques appelées désordres génomiques par opposition aux maladies géniques dues à des mutations intragéniques. L’étude de l’origine parentale et cellulaire des aneuploïdies éclaire d’un jour nouveau les mécanismes de contrôle de la méiose différents chez l’homme et chez la femme, ainsi que le rôle majeur de l’âge maternel et de la recombinaison pour la répartition méiotique correcte des chromosomes. Ces nouvelles données apportent des clés essentielles pour la compréhension des pathologies chromosomiques chez l’homme.
Summary
Novel methods allowing to analyze the human genome make it possible to assess old questions such as the molecular basis of structural chromosome anomalies and the diathesis to aneuploidy. The architecture of the human genome as unravelled by the human genome sequencing project allows to explain the recurrence of microdeletions and microduplications caused by a non allelic homologous recombination involving segmental duplications created during the evolution of primates. This structural feature of the human genome is associated with a novel class of genetic diseases called genomic disorders as opposed to genetic diseases due to gene mutations. The study of the parental and cellular origin of aneuploidy shed new light on the different mechanisms controlling meiosis in man and woman. In addition it contributes to define the role of maternal age and genetic recombination on the behavior of chromosomes during meiosis. These new data greatly contribute to our understanding of human chromosomal diseases.
Appendices
Références
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