Jacobs Journal of Genetics

Towards the Identification of Genetic Targets for Therapeutics of Intellectual Disability in Down syndrome

*Mohammed Rachidi
Molecular Genetics Of Human Diseases, University Paris 7 Denis Diderot, France

*Corresponding Author:
Mohammed Rachidi
Molecular Genetics Of Human Diseases, University Paris 7 Denis Diderot, France
Email:rachidi.med1@yahoo.com

Published on: 2018-11-02

Abstract

Down syndrome, or Trisomy 21, is the most frequent genetic cause of the intellectual disability, a cognitive disorder with hard impact on public health. The expression of this feature is due to the overexpression of the human chromosome 21 genes. The genetic dissection of the Down syndrome neurological phenotypes in trisomic mouse models greatly enhanced our understanding of cellular and molecular mechanisms of gene dosage effects and the associated signalling pathways involved in the morphological and functional brain alterations, and in the pathogenesis of intellectual disability towards the identification of molecular targets for clinical therapeutics.

Keywords

Introduction

Trisomy of human chromosome 21 (HSA21) is the most frequent genetic cause of mental retardation or intellectual disability and other variable phenotypic expression, including developmental defects, dysmorphic features, cognitive impairments and similar neurologic disorders seen in Alzheimer’s disease, collectively known as Down Syndrome (DS) affecting 1 in 700 live births [1]. In the most cases, DS results from an extra copy of chromosome 21 in all cells of the afflicted individuals. In some rare cases, DS results from a partial trisomy 21 showing variable phenotypes depending of triplicated region. Clinical, cytogenetic and molecular analysis of such patients allowed the identification of the minimal region or Down Syndrome Chromosomal Region (DSCR), at 21q22.2 sub-band, responsible for many features of DS, including intellectual disability [2,3]. Therefore, intellectual disability is the most prominent and invariable feature of DS and the most invalidating neuropathological aspect, with hard impact on public health, caused by the overdosage of HSA21 genes. Consequently, the transcriptional map of the DSCR [4], the complete sequencing of human chromosome 21 [5], the analysis of the transcriptional activity of HSA21 [6], the gene expression map of human chromosome 21 genes orthologues in the mouse [7], and the transcriptome analysis in DS patients and trisomic mouse models [8,9] facilitated the identification of DS candidate genes involved in functional brain alterations and intellectual disability [10].