PMID- 16307865
OWN - NLM
STAT- MEDLINE
DCOM- 20060703
LR  - 20191210
IS  - 0888-7543 (Print)
IS  - 0888-7543 (Linking)
VI  - 87
IP  - 2
DP  - 2006 Feb
TI  - Computational analysis and refinement of sequence structure on chromosome 22q11.2 
      region: application to the development of quantitative real-time PCR assay for 
      clinical diagnosis.
PG  - 290-7
AB  - The low-copy repeat (LCR) is a new class of repetitive DNA element and has been 
      implicated in many human disorders, including DiGeorge/velocardiofacial syndrome 
      (DGS/VCFS). It is now recognized that nonallelic homologous recombination (NAHR) 
      through LCRs flanking the chromosome 22q11.2 region leads to genome 
      rearrangements and results in the DGS/VCFS. To refine the structure and content 
      of chromosome 22q11.2 LCRs, we applied computational analysis to dissect 
      region-specific LCRs using publicly available sequences. Nine distinct duplicons 
      between 1.6 and 65 kb long and sharing >95% sequence identity were identified. 
      The presence of these sequence motifs supports the NAHR mechanism. Further 
      sequence analysis suggested that the previously defined 3-Mb deletion may 
      actually comprise two deletion intervals of similar size close to each other and 
      thus indistinguishable when using fluorescence in situ hybridization (FISH) 
      analysis. The differentially deleted regions contain several hypothetical 
      proteins and UniGene clusters and may partially explain the clinical 
      heterogeneity observed in DGS/VCFS patients with the 3-Mb common deletion. To 
      implement further sequence information in molecular medicine, we designed a 
      real-time quantitative PCR assay and validated the method in 122 patients with 
      suspected DGS/VCFS. The assay detected 28 patients with chromosome 22q11.2 
      deletion later confirmed using FISH. Our results indicated that the developed 
      assay is reliable as well as time and cost effective for clinical diagnosis of 
      chromosome 22q11.2 deletion. They also suggest that this methodology can be 
      applied to develop a molecular approach for clinical detection and diagnosis of 
      other genomic disorders.
FAU - Chen, Ying-Fan
AU  - Chen YF
AD  - Institute of Basic Medical Sciences, National Cheng Kung University Medical 
      College, Tainan 70101, Taiwan.
FAU - Kou, Po-Lin
AU  - Kou PL
FAU - Tsai, Shaw-Jenq
AU  - Tsai SJ
FAU - Chen, Ko-Fan
AU  - Chen KF
FAU - Chan, Hsiang-Han
AU  - Chan HH
FAU - Chen, Chung-Ming
AU  - Chen CM
FAU - Sun, H Sunny
AU  - Sun HS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20051122
PL  - United States
TA  - Genomics
JT  - Genomics
JID - 8800135
SB  - IM
MH  - *Chromosomes, Human, Pair 22
MH  - DiGeorge Syndrome/*genetics
MH  - Humans
MH  - Molecular Diagnostic Techniques/*methods
MH  - Polymerase Chain Reaction/*methods
EDAT- 2005/11/26 09:00
MHDA- 2006/07/04 09:00
CRDT- 2005/11/26 09:00
PHST- 2005/08/25 00:00 [received]
PHST- 2005/09/29 00:00 [revised]
PHST- 2005/10/06 00:00 [accepted]
PHST- 2005/11/26 09:00 [pubmed]
PHST- 2006/07/04 09:00 [medline]
PHST- 2005/11/26 09:00 [entrez]
AID - S0888-7543(05)00292-2 [pii]
AID - 10.1016/j.ygeno.2005.10.002 [doi]
PST - ppublish
SO  - Genomics. 2006 Feb;87(2):290-7. doi: 10.1016/j.ygeno.2005.10.002. Epub 2005 Nov 
      22.