PMID- 15834244
OWN - NLM
STAT- MEDLINE
DCOM- 20050811
LR  - 20191109
IS  - 1098-3600 (Print)
IS  - 1098-3600 (Linking)
VI  - 7
IP  - 4
DP  - 2005 Apr
TI  - Detection and calibration of microdeletions and microduplications by array-based 
      comparative genomic hybridization and its applicability to clinical genetic 
      testing.
PG  - 264-71
AB  - PURPOSE: Genome-wide telomere screening by fluorescence in situ hybridization 
      (FISH) has revealed that approximately 6% of unexplained mental retardation is 
      due to submicroscopic telomere imbalances. However, the use of FISH for telomere 
      screening is labor intensive and time consuming, given that 41 telomeres are 
      interrogated. We have evaluated the use of array-based Comparative Genomic 
      Hybridization (aCGH) as a more efficient tool for identifying telomere 
      rearrangements. METHODS: In this study, 102 individuals with unexplained mental 
      retardation, with either normal or abnormal FISH results, were selected for a 
      blinded retrospective study using aCGH. Results between the two methodologies 
      were compared to ascertain the ability of aCGH to be used in a clinical 
      diagnostics setting. RESULTS: We detected 100% of all imbalances previously 
      identified by FISH (n = 17) and identified two additional abnormalities, a 10q 
      telomere duplication and an interstitial duplication of 22q11. Interphase FISH 
      analysis verified all abnormal array results. We also demonstrated that aCGH can 
      accurately calibrate the size of telomere imbalances by using an array with 
      "molecular rulers" for the telomeric regions of 1p, 16p, 17p, and 22q. 
      CONCLUSION: This study demonstrates that aCGH is an equivalent methodology to 
      telomere FISH for detecting submicroscopic deletions. In addition, small 
      duplications that are not easily visible by FISH can be accurately detected using 
      aCGH. Because aCGH allows simultaneous interrogation of hundreds to thousands of 
      DNA probes and is more amenable to automation, it offers an efficient and 
      high-throughput alternative for detecting and calibrating unbalanced 
      rearrangements, both of the telomere region, as well as other genomic locations.
FAU - Wong, Andrew
AU  - Wong A
AD  - Department of Human Genetics, Emory University School of Medicine, Atlanta, 
      Georgia 30322, USA.
FAU - Lese Martin, Christa
AU  - Lese Martin C
FAU - Heretis, Konstantina
AU  - Heretis K
FAU - Ruffalo, Teresa
AU  - Ruffalo T
FAU - Wilber, Kim
AU  - Wilber K
FAU - King, Walter
AU  - King W
FAU - Ledbetter, David H
AU  - Ledbetter DH
LA  - eng
GR  - 5 R01 HD36715-03/HD/NICHD NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genet Med
JT  - Genetics in medicine : official journal of the American College of Medical 
      Genetics
JID - 9815831
SB  - IM
MH  - Chromosome Aberrations/*statistics & numerical data
MH  - Cytogenetic Analysis/*methods
MH  - Evaluation Studies as Topic
MH  - Genetic Testing/*methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Intellectual Disability/*genetics
MH  - Nucleic Acid Hybridization/methods
MH  - Retrospective Studies
MH  - Telomere/*genetics
EDAT- 2005/04/19 09:00
MHDA- 2005/08/12 09:00
CRDT- 2005/04/19 09:00
PHST- 2005/04/19 09:00 [pubmed]
PHST- 2005/08/12 09:00 [medline]
PHST- 2005/04/19 09:00 [entrez]
AID - 00125817-200504000-00006 [pii]
AID - 10.1097/01.gim.0000160076.14102.ec [doi]
PST - ppublish
SO  - Genet Med. 2005 Apr;7(4):264-71. doi: 10.1097/01.gim.0000160076.14102.ec.