Découvertes de variations du nombre de copies rares chez les personnes avec un diagnostic de "trouble du spectre de l'autisme"

Aperçu: G.M.  

L'indentification d'une variation du nombre de copies de novo rare et non héritée (CNVs) chez une personne est une approche productive qui souligne le risque génétique dans le "trouble du spectre de l'autisme" (TSA).

Une variété de micro-puces à ADN est capable de détecter des CNVs, incluant des matrices de polymorphisme de simple nucleotide (SNP) et des matrices d'hydridation génémique comparatives (CGH).

Ici, l'équipe examine une cohorte de 696 personnes avec un diagnostic de TSA non liés en utilisant une micro-puce à haute résolution d'un million CGH.

Cette cohorte clinique TSA largement phénotypée et génotypée sert de ressource inestimable pour la prochaine étape du séquençage du génome pour la détection complète de la variation génétique.

G3 (Bethesda). 2012 Dec;2(12):1665-85. doi: 10.1534/g3.112.004689. 

A discovery resource of rare copy number variations in individuals with autism spectrum disorder

Prasad A, Merico D, Thiruvahindrapuram B, Wei J, Lionel AC, Sato D, Rickaby J, Lu C, Szatmari P, Roberts W, Fernandez BA, Marshall CR, Hatchwell E, Eis PS,Scherer SW.

Source

The Centre for Applied Genomics, Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto M5G 1L7, Canada.

 Our objective was to discover new CNVs in ASD cases that were not detected by SNP microarray analysis and to delineate novel ASD risk loci via combined analysis of CGH and SNP array data sets on the ASD cohort and CGH data on an additional 1000 control samples. Of the 615 ASD cases analyzed on both SNP and CGH arrays, we found that 13,572 of 21,346 (64%) of the CNVs were exclusively detected by the CGH array. Several of the CGH-specific CNVs are rare in population frequency and impact previously reported ASD genes (e.g., NRXN1, GRM8, DPYD), as well as novel ASD candidate genes (e.g., CIB2, DAPP1, SAE1), and all were inherited except for a de novo CNV in the GPHN gene. A functional enrichment test of gene-sets in ASD cases over controls revealed nucleotide metabolism as a potential novel pathway involved in ASD, which includes several candidate genes for follow-up (e.g., DPYD, UPB1, UPP1, TYMP). Finally, this extensively phenotyped and genotyped ASD clinical cohort serves as an invaluable resource for the next step of genome sequencing for complete genetic variation detection.

Abstract

Source