PMID- 20561756
OWN - NLM
STAT- MEDLINE
DCOM- 20101202
LR  - 20100708
IS  - 1531-6564 (Electronic)
IS  - 0363-5023 (Linking)
VI  - 35
IP  - 7
DP  - 2010 Jul
TI  - Genome-wide high-resolution screening in Dupuytren's disease reveals common 
      regions of DNA copy number alterations.
PG  - 1172-1183.e7
LID - 10.1016/j.jhsa.2010.03.006 [doi]
AB  - PURPOSE: Dupuytren's disease (DD) is a familial disorder with a high genetic 
      susceptibility in white people; however, its etiopathogenesis remains unknown. 
      Previous comparative genomic hybridization studies using lower-resolution, 44-k 
      oligonucleotide-based arrays revealed no copy number variation (CNV) changes in 
      DD. In this study, we used a higher-resolution genome-wide screening 
      (next-generation microarrays) comprising 963,331 human sequences (3 kb spacing 
      between probes) for whole genome DNA variation analysis. The objective was to 
      detect cryptic chromosomal imbalances in DD. METHODS: Agilent SurePrint G3 
      microarrays, one million format (Agilent Technologies, Santa Clara, CA), were 
      used to detect CNV regions (CNVRs) in DNA extracted from nodules of 4 white men 
      with DD (age, 69 +/- 4 y). Reference samples were from the DNA of 10 men who 
      served as control patients. Copy number variations that were common to greater 
      than 3 assessed DD individuals (p < .05) were selected as candidate loci for DD 
      etiology. In addition, quantitative polymerase chain reactions (qPCR) assays were 
      designed for selected CNVRs on DNA from 13 DD patients and 11 control patients. 
      Independent t-tests and Fisher's exact tests were carried out for statistical 
      analysis. RESULTS: Three novel CNVs previously unreported in the phenotypically 
      normal population were detected in 3 DD cases, located at 10q22, 16p12.1, and 
      17p12. Nine polymorphic CNVRs potentially associated with DD were determined 
      using our strategic selection criteria, locating to chromosomes 1q31, 6p21, 7p14, 
      8p11, 12p13, 14q11, 17q21 and 20p13. More than 3 of the DD cases tested had a 
      CNVR located to a small region on 6p21 and 4 CNVRs within 6p21-22 of the human 
      leukocyte antigen (HLA) genes. CONCLUSIONS: Three novel copy number alterations 
      were observed in 3 unrelated patients with sporadic (no known family history) DD. 
      Nine polymorphic CNVRs were found to be common among the DD cases. These variants 
      might contain genes involved in DD formation, indicating that important gene 
      networks expressed within the palmar fascia might contribute to genetic 
      susceptibility of DD.
CI  - Copyright 2010. Published by Elsevier Inc.
FAU - Shih, Barbara B
AU  - Shih BB
AD  - Plastic and Reconstructive Surgery Research, School of Translational Medicine, 
      Manchester Interdisciplinary Biocentre, University of Manchester, Manchester 
      M17ND, UK.
FAU - Tassabehji, May
AU  - Tassabehji M
FAU - Watson, James S
AU  - Watson JS
FAU - McGrouther, Angus D
AU  - McGrouther AD
FAU - Bayat, Ardeshir
AU  - Bayat A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20100619
PL  - United States
TA  - J Hand Surg Am
JT  - The Journal of hand surgery
JID - 7609631
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Aged
MH  - Case-Control Studies
MH  - Comparative Genomic Hybridization
MH  - DNA/genetics
MH  - DNA Copy Number Variations/*genetics
MH  - Dupuytren Contracture/*genetics
MH  - *Genetic Predisposition to Disease
MH  - Genetic Testing
MH  - Genome, Human/genetics
MH  - Humans
MH  - Male
MH  - Microarray Analysis
MH  - Polymerase Chain Reaction/methods
MH  - Reference Values
EDAT- 2010/06/22 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/06/22 06:00
PHST- 2009/11/02 00:00 [received]
PHST- 2010/02/27 00:00 [revised]
PHST- 2010/03/03 00:00 [accepted]
PHST- 2010/06/22 06:00 [entrez]
PHST- 2010/06/22 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - S0363-5023(10)00268-6 [pii]
AID - 10.1016/j.jhsa.2010.03.006 [doi]
PST - ppublish
SO  - J Hand Surg Am. 2010 Jul;35(7):1172-1183.e7. doi: 10.1016/j.jhsa.2010.03.006. 
      Epub 2010 Jun 19.