title: The intellectual disability of trisomy 21: differences in gene expression in a case series of patients with lower and higher IQ.
abstract: Trisomy 21 (T21), or Down syndrome (DS), is the most frequent and recognizable cause of intellectual disabilities. The level of disability, as evaluated by the intelligence quotient (IQ) test, varies considerably between patients independent of other factors. To determine the genetic or molecular basis of this difference, a high throughput transcriptomic analysis was performed on twenty T21 patients with high and low IQ, and 10 healthy controls using Digital Gene Expression. More than 90 millions of tags were sequenced in the three libraries. A total of 80 genes of potential interest were selected for the qPCR experiment validation, and three housekeeping genes were used for normalizing purposes. HLA DQA1 and HLA DRB1 were significantly downregulated among the patients with a low IQ, the values found in the healthy controls being intermediate between those noted in the IQ+ and IQ- T21 patients. Interestingly, the intergenic region between these genes contains a binding sequence for the CCCTC-binding factor, or CTCF, and cohesin (a multisubunit complex), both of which are essential for expression of HLA DQA1 and HLA DRB1 and numerous other genes. Our results might lead to the discovery of genes, or genetic markers, that are directly involved in several phenotypes of DS and, eventually, to the identification of potential targets for therapeutic interventions.
authors: 1] Institut Jérôme Lejeune, Paris, France [2] Unité de Génétique Médicale et Laboratoire Associé INSERM UMR_S910, Beirut, Lebanon.
authors: André
authors: A
authors: Mégarbané
authors: Florian
authors: F
authors: Noguier
authors: Samantha
authors: S
authors: Stora
authors: Laurent
authors: L
authors: Manchon
authors: Clotilde
authors: C
authors: Mircher
authors: Roman
authors: R
authors: Bruno
authors: Nathalie
authors: N
authors: Dorison
authors: Fabien
authors: F
authors: Pierrat
authors: Marie-Odile
authors: MO
authors: Rethoré
authors: Bernadette
authors: B
authors: Trentin
authors: Aimé
authors: A
authors: Ravel
authors: Marine
authors: M
authors: Morent
authors: Gerard
authors: G
authors: Lefranc
authors: David
authors: D
authors: Piquemal
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D004314:Down Syndrome / Q000097:blood / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000097:blood / Q000235:genetics*; D007361:Intelligence Tests; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D059811:HLA-DRB1 Chains; D012333:RNA, Messenger