PMID- 17632771
OWN - NLM
STAT- MEDLINE
DCOM- 20071109
LR  - 20200930
IS  - 1552-4825 (Print)
IS  - 1552-4825 (Linking)
VI  - 143A
IP  - 16
DP  - 2007 Aug 15
TI  - The clinical utility of enhanced subtelomeric coverage in array CGH.
PG  - 1850-7
AB  - Telomeric chromosome abnormalities are a substantial cause of mental retardation 
      and birth defects. Although subtelomeric fluorescence in situ hybridization 
      (FISH) probes have been widely used to identify submicroscopic telomeric 
      rearrangements, array-based comparative genomic hybridization (array CGH) has 
      emerged as a more efficient and comprehensive detection method. Due to the 
      clinical relevance of telomeric abnormalities, it has been proposed that array 
      CGH using panels of BAC clones that map to regularly spaced intervals along the 
      length of each telomere could be used to characterize subtelomeric aberrations 
      more precisely in a single experiment. We have added 1,120 FISH-mapped BAC clones 
      to our microarray to enhance the coverage of the 41 unique human subtelomeric 
      regions. Contigs of clones were selected in increments of approximately 0.5 Mb 
      beginning with the most distal unique sequence for each subtelomere and extending 
      on average approximately 5.7 Mb toward the centromere. We have used this 
      microarray to characterize 169 clinically significant subtelomeric abnormalities 
      identified out of nearly 7,000 consecutive clinical cases analyzed by array CGH 
      in our diagnostic laboratory. The expanded telomere coverage was sufficient to 
      define the breakpoints of over half (56%) of the chromosome abnormalities. 
      However, 44% of the subtelomeric aberrations extended beyond the size of this 
      expanded coverage suggesting that many subtelomeric abnormalities are >5 Mb in 
      size and that greater representation may be of even more value. In addition to 
      identifying 6 cases of complex rearrangements, we have identified 42 cases of 
      interstitial deletions that would have been missed by subtelomere FISH panels 
      that use a single clone to the most distal unique sequence for each region. 
      Microarrays designed to investigate regions known to be involved in chromosome 
      abnormalities will enhance the detection of cytogenetic abnormalities at 
      unprecedented resolution and frequency.
CI  - (c) 2007 Wiley-Liss, Inc.
FAU - Ballif, Blake C
AU  - Ballif BC
AD  - Signature Genomic Laboratories, LLC, Spokane, Washington 99202, USA. 
      ballif@signaturegenomics.com
FAU - Sulpizio, Scott G
AU  - Sulpizio SG
FAU - Lloyd, Richard M
AU  - Lloyd RM
FAU - Minier, Sara L
AU  - Minier SL
FAU - Theisen, Aaron
AU  - Theisen A
FAU - Bejjani, Bassem A
AU  - Bejjani BA
FAU - Shaffer, Lisa G
AU  - Shaffer LG
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
SB  - IM
MH  - Chromosome Disorders/*diagnosis/genetics
MH  - Female
MH  - Humans
MH  - Male
MH  - Oligonucleotide Array Sequence Analysis/*methods
MH  - Phenotype
MH  - Telomere/*genetics
EDAT- 2007/07/17 09:00
MHDA- 2007/11/10 09:00
CRDT- 2007/07/17 09:00
PHST- 2007/07/17 09:00 [pubmed]
PHST- 2007/11/10 09:00 [medline]
PHST- 2007/07/17 09:00 [entrez]
AID - 10.1002/ajmg.a.31842 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2007 Aug 15;143A(16):1850-7. doi: 10.1002/ajmg.a.31842.