High-resolution mapping and analysis of copy number variations in the human genome: a data resource for clinical and research applications.
We present a database of copy number variations (CNVs) detected in 2026 disease-free individuals, using high-density, SNP-based oligonucleotide microarrays. This large cohort, comprised mainly of Caucasians (65.2%) and African-Americans (34.2%), was analyzed for CNVs in a single study using a uniform array platform and computational process. We have catalogued and characterized 54,462 individual CNVs, 77.8% of which were identified in multiple unrelated individuals. These nonunique CNVs mapped to 3272 distinct regions of genomic variation spanning 5.9% of the genome; 51.5% of these were previously unreported, and >85% are rare. Our annotation and analysis confirmed and extended previously reported correlations between CNVs and several genomic features such as repetitive DNA elements, segmental duplications, and genes. We demonstrate the utility of this data set in distinguishing CNVs with pathologic significance from normal variants. Together, this analysis and annotation provides a useful resource to assist with the assessment of CNVs in the contexts of human variation, disease susceptibility, and clinical molecular diagnostics.
Shaikh
Tamim H
TH
Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Gai
Xiaowu
X
Perin
Juan C
JC
Glessner
Joseph T
JT
Xie
Hongbo
H
Murphy
Kevin
K
O'Hara
Ryan
R
Casalunovo
Tracy
T
Conlin
Laura K
LK
D'Arcy
Monica
M
Frackelton
Edward C
EC
Geiger
Elizabeth A
EA
Haldeman-Englert
Chad
C
Imielinski
Marcin
M
Kim
Cecilia E
CE
Medne
Livija
L
Annaiah
Kiran
K
Bradfield
Jonathan P
JP
Dabaghyan
Elvira
E
Eckert
Andrew
A
Onyiah
Chioma C
CC
Ostapenko
Svetlana
S
Otieno
F George
FG
Santa
Erin
E
Shaner
Julie L
JL
Skraban
Robert
R
Smith
Ryan M
RM
Elia
Josephine
J
Goldmuntz
Elizabeth
E
Spinner
Nancy B
NB
Zackai
Elaine H
EH
Chiavacci
Rosetta M
RM
Grundmeier
Robert
R
Rappaport
Eric F
EF
Grant
Struan F A
SF
White
Peter S
PS
Hakonarson
Hakon
H
D000328:Adult; D044383:Black People / Q000235:genetics; D002648:Child; D002874:Chromosome Mapping / Q000379:methods*; D030541:Databases, Genetic; D018628:Gene Dosage / Q000235:genetics*; D020440:Gene Duplication; D014644:Genetic Variation; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012107:Research Design; D044465:White People / Q000235:genetics; D001741:Black or African American