hotspots of large rare deletions in the human genome热点地区的大型罕见的在人类基因组中删除.pdfVIP

Hotspots of Large Rare Deletions in the Human Genome 1 2. 2. ´ 2 ´ ` 2 W. Edward C. Bradley *, John V. Raelson , Daniel Y. Dubois , Eric Godin , Helene Fournier , Charles ´ 2 ´ 2 2 2 ´ 2 Prive , Rene Allard , Vadym Pinchuk , Micheline Lapalme , Rene J. A. Paulussen , Abdelmajid Belouchi1,2 ´ ´ ´ 1 Department of Medicine, Universite de Montreal, Montreal, Quebec, Canada, 2 Genizon Biosciences, Inc., St. Laurent, Quebec, Canada Abstract Background: We have examined the genomic distribution of large rare autosomal deletions in a sample of 440 parent- parent-child trios from the Quebec founder population (QFP) which was recruited for a study of Attention Deficit Hyperactivity Disorder. Methodology/Principal Findings: DNA isolated from blood was genotyped on Illumina Hap300 arrays. PennCNV combined with visual evaluation of images generated by the Beadstudio program was used to determine deletion boundary definition of sufficient precision to discern independent events, with near-perfect concordance between parent and child in about 98% of the 399 events detected in the offspring; the remaining 7 deletions were considered de novo. We defined several genomic regions of very high deletion frequency (‘hotspots’), usually of 0.4–0.6 Mb in length where independent rare deletions were found at frequencies of up to 100 fold higher than the average for the genome as a whole. Five of the 7 de novo deletions were in these hotspots. The same hotspots were also observed in thr