Human chromosome 21 sequence: impact for the molecular genetics of Down syndrome

Abstract

More than one century after the discovery of trisomy 21, the molecular mechanisms underlying the complex phenotype associated with Down syndrome (DS) remain unknown. Up to now, the molecular consequences of gene-dosage imbalance have been mainly investigated by the definition of DS critical regions, based on phenotype-genotype correlations established for rare cases of partial trisomy 21. Recently, the generation of trisomic mouse models has opened interesting possibilities for studying components of the DS phenotype, addressing in particular the cerebellar pathology. The complete DNA sequence, clone map, and gene catalogue of chromosome 21 offers new molecular tools for revisiting phenotype-genotype correlations and for dissecting the molecular bases of DS pathogenesis, using strategic technologies that will allow to define molecular profiles of trisomy 21.