A large data resource of genomic copy number variation across neurodevelopmental disorders

被引：111

作者：

Zarrei, Mehdi ^{[1
,2
]}

Burton, Christie L. ^{[3
]}

Engchuan, Worrawat ^{[1
,2
]}

Young, Edwin J. ^{[4
]}

Higginbotham, Edward J. ^{[1
,2
,5
]}

MacDonald, Jeffrey R. ^{[1
]}

Trost, Brett ^{[1
,2
]}

Chan, Ada J. S. ^{[1
,2
,5
]}

Walker, Susan ^{[1
]}

Lamoureux, Sylvia ^{[1
]}

Heung, Tracy ^{[6
]}

Mojarad, Bahareh A. ^{[2
]}

Kellam, Barbara ^{[1
]}

Paton, Tara ^{[1
]}

Faheem, Muhammad ^{[1
,2
]}

Miron, Karin ^{[1
,2
]}

Lu, Chao ^{[1
]}

Wang, Ting ^{[1
]}

Samler, Kozue ^{[1
]}

Wang, Xiaolin ^{[1
]}

Costain, Gregory ^{[7
,8
]}

Hoang, Ny ^{[2
,5
,9
]}

Pellecchia, Giovanna ^{[1
]}

Wei, John ^{[1
]}

Patel, Rohan, V ^{[1
]}

Thiruvahindrapuram, Bhooma ^{[1
]}

Roifman, Maian ^{[7
,10
,11
]}

Merico, Daniele ^{[1
,12
]}

Goodale, Tara ^{[3
]}

Drmic, Irene ^{[13
]}

Speevak, Marsha ^{[14
]}

Howe, Jennifer L. ^{[1
]}

Yuen, Ryan K. C. ^{[1
,2
]}

Buchanan, Janet A. ^{[1
]}

Vorstman, Jacob A. S. ^{[15
,16
]}

Marshall, Christian R. ^{[1
,4
,17
]}

Wintle, Richard F. ^{[1
]}

Rosenberg, David R. ^{[18
,19
]}

Hanna, Gregory L. ^{[20
]}

Woodbury-Smith, Marc ^{[1
,21
]}

Cytrynbaum, Cheryl ^{[2
,5
,7
,22
,23
]}

Zwaigenbaum, Lonnie ^{[24
]}

Elsabbagh, Mayada ^{[25
]}

Flanagan, Janine ^{[11
]}

Fernandez, Bridget A. ^{[26
]}

Carter, Melissa T. ^{[27
]}

Szatmari, Peter ^{[15
,28
,29
]}

Roberts, Wendy ^{[16
]}

Lerch, Jason ^{[30
,31
]}

Liu, Xudong ^{[32
]}

机构：

[1] Hosp Sick Children, Ctr Appl Genom, Toronto, ON, Canada

[2] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON, Canada

[3] Hosp Sick Children, Neurosci & Mental Hlth Program, Toronto, ON, Canada

[4] Hosp Sick Children, Dept Paediat Lab Med, Genome Diagnost, Toronto, ON, Canada

[5] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[6] Ctr Addict & Mental Hlth, Clin Genet Res Program, Toronto, ON, Canada

[7] Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON, Canada

[8] Univ Toronto, Med Genet Residency Training Program, Toronto, ON, Canada

[9] Hosp Sick Children, Dept Genet Counselling, Toronto, ON, Canada

[10] Mt Sinai Hosp, Dept Obstet & Gynecol, Prenatal Diag & Med Genet Program, Toronto, ON, Canada

[11] Univ Toronto, Dept Paediat, Toronto, ON, Canada

[12] Deep Genom Inc, Toronto, ON, Canada

[13] Ron Joyce Childrens Hlth Ctr, Hamilton Hlth Sci, Hamilton, ON, Canada

[14] Trillium Hlth Partners Credit Valley Site, Mississauga, ON, Canada

[15] Univ Toronto, Dept Psychiat, Toronto, ON, Canada

[16] Hosp Sick Children, Autism Res Unit, Toronto, ON, Canada

[17] Univ Toronto, Lab Med & Pathobiol, Toronto, ON, Canada

[18] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48207 USA

[19] Childrens Hosp Michigan, Detroit, MI 48201 USA

[20] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA

[21] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne, Tyne & Wear, England

[22] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada

[23] Univ Toronto, Dept Family & Community Med, Toronto, ON, Canada

[24] Univ Alberta, Dept Pediat, Edmonton, AB, Canada

[25] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada

[26] Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF, Canada

[27] Childrens Hosp Eastern Ontario, Reg Genet Program, Ottawa, ON, Canada

[28] Ctr Addict & Mental Hlth, Toronto, ON, Canada

[29] Hosp Sick Children, Dept Psychiat, Toronto, ON, Canada

[30] Hosp Sick Children, Mouse Imaging Ctr, Toronto, ON, Canada

[31] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[32] Queens Univ, Dept Psychiat, Kinston, ON, Canada

[33] Childrens Hlth Res Inst, London, ON, Canada

[34] Western Univ, London, ON, Canada

[35] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada

[36] Univ Calgary, Mathison Ctr Mental Hlth Res & Educ, Calgary, AB, Canada

[37] Univ Calgary, Cumming Sch Med, Dept Psychiat, Calgary, AB, Canada

[38] Univ Calgary, Cumming Sch Med, Dept Med Genet, Calgary, AB, Canada

[39] Toronto Gen Hosp, Dalglish Family Clin 22q, Toronto, ON, Canada

[40] Univ Toronto, Inst Med Sci, Toronto, ON, Canada

[41] Univ Toronto, Holland Bloorview Kids Rehabil Hosp, Toronto, ON, Canada

[42] Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada

来源：

NPJ GENOMIC MEDICINE | 2019年 / 4卷 / 1期

基金：

加拿大健康研究院; 美国国家卫生研究院; 加拿大创新基金会;

关键词：

AUTISM SPECTRUM DISORDER; CANDIDATE GENES; IDENTIFICATION; INDIVIDUALS; MICROARRAY; DELETIONS; VARIANTS; MAP;

D O I：

10.1038/s41525-019-0098-3

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents. We identified rare CNVs, defined as those found in <0.1% of 10,851 population control samples. We found clinically relevant CNVs (broadly defined) in 284 (10.5%) of total subjects, including 22 (10.8%) among subjects with SCZ, 209 (11.4%) with ASD, 40 (9.4%) with ADHD, and 13 (5.6%) with OCD. Among all NDD subjects, we identified 17 (0.63%) with aneuploidies and 115 (43%) with known genomic disorder variants. We searched further for genes impacted by different CNVs in multiple disorders. Examples of NDD-associated genes linked across more than one disorder (listed in order of occurrence frequency) are NRXN1, SEH1L, LDLRAD4, GNAL, GNG13, MKRN1, DCTN2, KNDC1, PCMTD2, KIF5A, SYNM, and long non-coding RNAs: AK127244 and PTCHD1-AS. We demonstrated that CNVs impacting the same genes could potentially contribute to the etiology of multiple NDDs. The CNVs identified will serve as a useful resource for both research and diagnostic laboratories for prioritization of variants.

引用

页数：13

共 50 条

[1] A large data resource of genomic copy number variation across neurodevelopmental disorders
Mehdi Zarrei
Christie L. Burton
Worrawat Engchuan
Edwin J. Young
Edward J. Higginbotham
Jeffrey R. MacDonald
Brett Trost
Ada J. S. Chan
Susan Walker
Sylvia Lamoureux
Tracy Heung
Bahareh A. Mojarad
Barbara Kellam
Tara Paton
Muhammad Faheem
Karin Miron
Chao Lu
Ting Wang
Kozue Samler
Xiaolin Wang
Gregory Costain
Ny Hoang
Giovanna Pellecchia
John Wei
Rohan V. Patel
Bhooma Thiruvahindrapuram
Maian Roifman
Daniele Merico
Tara Goodale
Irene Drmic
Marsha Speevak
Jennifer L. Howe
Ryan K. C. Yuen
Janet A. Buchanan
Jacob A. S. Vorstman
Christian R. Marshall
Richard F. Wintle
David R. Rosenberg
Gregory L. Hanna
Marc Woodbury-Smith
Cheryl Cytrynbaum
Lonnie Zwaigenbaum
Mayada Elsabbagh
Janine Flanagan
Bridget A. Fernandez
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