A copy number variation morbidity map of developmental delay

被引：999

作者：

Cooper, Gregory M. ^{[1
]}

Coe, Bradley P. ^{[1
]}

Girirajan, Santhosh ^{[1
]}

Rosenfeld, Jill A. ^{[2
]}

Vu, Tiffany H. ^{[1
]}

Baker, Carl ^{[1
]}

Williams, Charles ^{[3
]}

Stalker, Heather ^{[3
]}

Hamid, Rizwan ^{[4
]}

Hannig, Vickie ^{[4
]}

Abdel-Hamid, Hoda ^{[5
]}

Bader, Patricia ^{[6
]}

McCracken, Elizabeth ^{[7
]}

Niyazov, Dmitriy ^{[8
]}

Leppig, Kathleen ^{[9
]}

Thiese, Heidi ^{[9
]}

Hummel, Marybeth ^{[10
]}

Alexander, Nora ^{[10
]}

Gorski, Jerome ^{[11
]}

Kussmann, Jennifer ^{[11
]}

Shashi, Vandana ^{[12
]}

Johnson, Krys ^{[13
]}

Rehder, Catherine ^{[14
]}

Ballif, Blake C. ^{[1
,2
]}

Shaffer, Lisa G. ^{[2
]}

Eichler, Evan E. ^{[15
]}

机构：

[1] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[2] Signature Genom Labs LLC, Spokane, WA USA

[3] Univ Florida, Dept Pediat, Div Genet, Gainesville, FL USA

[4] Vanderbilt Univ, Med Ctr, Nashville, TN USA

[5] Univ Pittsburgh, Dept Pediat, Div Child Neurol, Pittsburgh, PA 15260 USA

[6] NE Indiana Genet Counseling Ctr, Ft Wayne, IN USA

[7] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA

[8] Ochsner Clin & Alton Ochsner Med Fdn, New Orleans, LA USA

[9] Grp Hlth Cooperat Puget Sound, Seattle, WA USA

[10] W Virginia Univ, Morgantown, WV 26506 USA

[11] Univ Missouri, Columbia, MO USA

[12] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA

[13] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA

[14] Duke Univ Hlth Syst, Clin Mol Diagnost Lab, Durham, NC USA

[15] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA

来源：

NATURE GENETICS | 2011年 / 43卷 / 09期

基金：

美国国家卫生研究院; 加拿大健康研究院; 英国惠康基金;

关键词：

RARE CHROMOSOMAL DELETIONS; HOLT-ORAM SYNDROME; HUMAN GENOME; STRUCTURAL VARIATION; INCREASE RISK; ARRAY CGH; SCHIZOPHRENIA; COMMON; MICRODELETION; GENES;

D O I：

10.1038/ng.909

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

To understand the genetic heterogeneity underlying developmental delay, we compared copy number variants (CNVs) in 15,767 children with intellectual disability and various congenital defects (cases) to CNVs in 8,329 unaffected adult controls. We estimate that similar to 14.2% of disease in these children is caused by CNVs >400 kb. We observed a greater enrichment of CNVs in individuals with craniofacial anomalies and cardiovascular defects compared to those with epilepsy or autism. We identified 59 pathogenic CNVs, including 14 new or previously weakly supported candidates, refined the critical interval for several genomic disorders, such as the 17q21.31 microdeletion syndrome, and identified 940 candidate dosage-sensitive genes. We also developed methods to opportunistically discover small, disruptive CNVs within the large and growing diagnostic array datasets. This evolving CNV morbidity map, combined with exome and genome sequencing, will be critical for deciphering the genetic basis of developmental delay, intellectual disability and autism spectrum disorders.

引用

页码：838 / U44

页数：11

共 60 条

[1]

Effect of statin therapy on C-reactive protein levels - The Pravastatin Inflammation/CRP Evaluation (PRINCE): A randomized trial and cohort study [J].

Albert, MA ;

Danielson, E ;

Rifai, N ;

Ridker, PM .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2001, 286 (01) :64-70

[2]

Human Cleft Lip and Palate Fibroblasts and Normal Nicotine-Treated Fibroblasts Show Altered In Vitro Expressions of Genes Related to Molecular Signaling Pathways and Extracellular Matrix Metabolism [J].

Baroni, Tiziano ;

Bellucci, Catia ;

Lilli, Cinzia ;

Pezzetti, Furio ;

Carinci, Francesco ;

Lumare, Eleonora ;

Palmieri, Annalisa ;

Stabellini, Giordano ;

Bodo, Maria .

JOURNAL OF CELLULAR PHYSIOLOGY, 2010, 222 (03) :748-756

[3]

Mutations in human cause limb and cardiac malformation in Holt-Oram syndrome [J].

Basson, CT ;

Bachinsky, DR ;

Lin, RC ;

Levi, T ;

Elkins, JA ;

Soults, J ;

Grayzel, D ;

Kroumpouzou, E ;

Traill, TA ;

LeblancStraceski, J ;

Renault, B ;

Kucherlapati, R ;

Seidman, JG ;

Seidman, CE .

NATURE GENETICS, 1997, 15 (01) :30-35

[4]

Large, rare chromosomal deletions associated with severe early-onset obesity [J].

Bochukova, Elena G. ;

Huang, Ni ;

Keogh, Julia ;

Henning, Elana ;

Purmann, Carolin ;

Blaszczyk, Kasia ;

Saeed, Sadia ;

Hamilton-Shield, Julian ;

Clayton-Smith, Jill ;

O'Rahilly, Stephen ;

Hurles, Matthew E. ;

Farooqi, I. Sadaf .

NATURE, 2010, 463 (7281) :666-670

[5]

Detection of Clinically Relevant Exonic Copy-Number Changes by Array CGH [J].

Boone, Philip M. ;

Bacino, Carlos A. ;

Shaw, Chad A. ;

Eng, Patricia A. ;

Hixson, Patricia M. ;

Pursley, Amber N. ;

Kang, Sung-Hae L. ;

Yang, Yaping ;

Wiszniewska, Joanna ;

Nowakowska, Beata A. ;

del Gaudio, Daniela ;

Xia, Zhilian ;

Simpson-Patel, Gayle ;

Immken, LaDonna L. ;

Gibson, James B. ;

Tsai, Anne C. -H. ;

Bowers, Jennifer A. ;

Reimschisel, Tyler E. ;

Schaaf, Christian P. ;

Potocki, Lorraine ;

Scaglia, Fernando ;

Gambin, Tomasz ;

Sykulski, Maciej ;

Bartnik, Magdalena ;

Derwinska, Katarzyna ;

Wisniowiecka-Kowalnik, Barbara ;

Lalani, Seema R. ;

Probst, Frank J. ;

Bi, Weimin ;

Beaudet, Arthur L. ;

Patel, Ankita ;

Lupski, James R. ;

Cheung, Sau Wai ;

Stankiewicz, Pawel .

HUMAN MUTATION, 2010, 31 (12) :1326-1342

[6]

Altered gene expression in the superior temporal gyrus in schizophrenia [J].

Bowden, Nikola A. ;

Scott, Rodney J. ;

Tooney, Paul A. .

BMC GENOMICS, 2008, 9 (1)

[7]

Comprehensive proteomic analysis of human par protein complexes reveals an interconnected protein network [J].

Brajenovic, M ;

Joberty, G ;

Küster, B ;

Bouwmeester, T ;

Drewes, G .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (13) :12804-12811

[8]

PRENATAL ULTRASOUND DIAGNOSIS OF THE HOLT-ORAM SYNDROME [J].

BRONS, JTJ ;

VANGEIJN, HP ;

WLADIMIROFF, JW ;

VANDERHARTEN, JJ ;

KWEE, ML ;

SOBOTKAPLOJHAR, M ;

ARTS, NFT .

PRENATAL DIAGNOSIS, 1988, 8 (03) :175-181

[9]

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[10]

Clinical report - De Novo trisomy 20p of paternal origin [J].

Chaabouni, Myriam ;

Turleau, Catherine ;

Karboul, Lotfi ;

Ben Jemaa, Lamia ;

Maazoul, Faouzi ;

Attie-Bitach, Tania ;

Romana, Serge ;

Chaabouni, Habiba .

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2007, 143A (10) :1100-1103

← 1 2 3 4 5 6 →