Identification of non-recurrent submicroscopic genome imbalances: the advantage of genome-wide microarrays over targeted approaches.
Genome-wide analysis of DNA copy-number changes using microarray-based technologies has enabled the detection of de novo cryptic chromosome imbalances in approximately 10% of individuals with mental retardation. So far, the majority of these submicroscopic microdeletions/duplications appear to be unique, hampering clinical interpretation and genetic counselling. We hypothesised that the genomic regions involved in these de novo submicroscopic aberrations would be candidates for recurrent copy-number changes in individuals with mental retardation. To test this hypothesis, we used multiplex ligation-dependent probe amplification (MLPA) to screen for copy number changes at eight genomic candidate regions in a European cohort of 710 individuals with idiopathic mental retardation. By doing so, we failed to detect additional submicroscopic rearrangements, indicating that the anomalies tested are non-recurrent in this cohort of patients. The break points flanking the candidate regions did not contain low copy repeats and/or sequence similarities, thus providing an explanation for its non-recurrent nature. On the basis of these data, we propose that the use of genome-wide microarrays is indicated when testing for copy-number changes in individuals with idiopathic mental retardation.
Koolen
David A
DA
Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Sistermans
Erik A
EA
Nilessen
Willy
W
Knight
Samantha J L
SJ
Regan
Regina
R
Liu
Yan T
YT
Kooy
R Frank
RF
Rooms
Liesbeth
L
Romano
Corrado
C
Fichera
Marco
M
Schinzel
Albert
A
Baumer
Alessandra
A
Anderlid
Britt-Marie
BM
Schoumans
Jacqueline
J
van Kessel
Ad Geurts
AG
Nordenskjold
Magnus
M
de Vries
Bert B A
BB
D001483:Base Sequence; D002874:Chromosome Mapping; D015331:Cohort Studies; D017931:DNA Primers; D015894:Genome, Human; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D022521:Ligase Chain Reaction; D020411:Oligonucleotide Array Sequence Analysis
D017931:DNA Primers