Relative Burden of Large CNVs on a Range of Neurodevelopmental Phenotypes 英文参考文献.docVIP

RelativeBurdenofLargeCNVsonaRangeof NeurodevelopmentalPhenotypes SanthoshGirirajan1,ZoranBrkanac2,BradleyP.Coe1,CarlBaker1,LauraVives1,TiffanyH.Vu1 ,Neil Shafer1,RaphaelBernier2,GiovanniB.Ferrero3,MargheritaSilengo3,StephenT.Warren4,CarlosS. Moreno5,MarcoFichera6,CorradoRomano6,WendyH.Raskind2,7,EvanE.Eichler1,8 * 1 Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, United States of America, 2 Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, United States of America,3 Department of Pediatrics, University of Torino, Turin, Italy,4 Departments of Human Genetics, Biochemistry, and Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America,5 Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America,6 IRCCS Associazione Oasi Maria Santissima, Troina, Italy,7 Department of Medicine, Division of Medical Genetics, University of Washington School of Medicine, Seattle, Washington, United States of America, 8 Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, Washington, United States of America Abstract While numerous studies have implicated copy number variants (CNVs) in a range of neurological phenotypes, the impact relative to disease severity has been difficult to ascertain due to small sample sizes, lack of phenotypic details, and heterogeneity in platforms used for discovery. Using a customized microarray enriched for genomic hotspots, we assayed for large CNVs among 1,227 individuals with various neurological deficits including dyslexia (376), sporadic autism (350), and intellectual disability (ID) (501), as well as 337 controls. We show that the frequency of large CNVs (.1 Mbp) is significantly greater