Oligonucleotide microarray analysis of genomic imbalance in children with mental retardation.
The cause of mental retardation in one-third to one-half of all affected individuals is unknown. Microscopically detectable chromosomal abnormalities are the most frequently recognized cause, but gain or loss of chromosomal segments that are too small to be seen by conventional cytogenetic analysis has been found to be another important cause. Array-based methods offer a practical means of performing a high-resolution survey of the entire genome for submicroscopic copy-number variants. We studied 100 children with idiopathic mental retardation and normal results of standard chromosomal analysis, by use of whole-genome sampling analysis with Affymetrix GeneChip Human Mapping 100K arrays. We found de novo deletions as small as 178 kb in eight cases, de novo duplications as small as 1.1 Mb in two cases, and unsuspected mosaic trisomy 9 in another case. This technology can detect at least twice as many potentially pathogenic de novo copy-number variants as conventional cytogenetic analysis can in people with mental retardation.
Friedman
J M
JM
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada. frid@interchange.ubc.ca
Baross
Agnes
A
Delaney
Allen D
AD
Ally
Adrian
A
Arbour
Laura
L
Armstrong
Linlea
L
Asano
Jennifer
J
Bailey
Dione K
DK
Barber
Sarah
S
Birch
Patricia
P
Brown-John
Mabel
M
Cao
Manqiu
M
Chan
Susanna
S
Charest
David L
DL
Farnoud
Noushin
N
Fernandes
Nicole
N
Flibotte
Stephane
S
Go
Anne
A
Gibson
William T
WT
Holt
Robert A
RA
Jones
Steven J M
SJ
Kennedy
Giulia C
GC
Krzywinski
Martin
M
Langlois
Sylvie
S
Li
Haiyan I
HI
McGillivray
Barbara C
BC
Nayar
Tarun
T
Pugh
Trevor J
TJ
Rajcan-Separovic
Evica
E
Schein
Jacqueline E
JE
Schnerch
Angelique
A
Siddiqui
Asim
A
Van Allen
Margot I
MI
Wilson
Gary
G
Yong
Siu-Li
SL
Zahir
Farah
F
Eydoux
Patrice
P
Marra
Marco A
MA
D002648:Child; D002869:Chromosome Aberrations; D018628:Gene Dosage; D015894:Genome, Human; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis*; D020411:Oligonucleotide Array Sequence Analysis; D017384:Sequence Deletion