PMID- 18374296
OWN - NLM
STAT- MEDLINE
DCOM- 20080513
LR  - 20230513
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 82
IP  - 4
DP  - 2008 Apr
TI  - FISH mapping of de novo apparently balanced chromosome rearrangements identifies 
      characteristics associated with phenotypic abnormality.
PG  - 916-26
LID - 10.1016/j.ajhg.2008.02.007 [doi]
AB  - We report fluorescence in situ hybridization (FISH) mapping of 152, mostly de 
      novo, apparently balanced chromosomal rearrangement (ABCR) breakpoints in 76 
      individuals, 30 of whom had no obvious phenotypic abnormality (control group) and 
      46 of whom had an associated disease (case group). The aim of this study was to 
      identify breakpoint characteristics that could discriminate between these groups 
      and which might be of predictive value in de novo ABCR (DN-ABCR) cases detected 
      antenatally. We found no difference in the proportion of breakpoints that 
      interrupted a gene, although in three cases, direct interruption or deletion of 
      known autosomal-dominant or X-linked recessive Mendelian disease genes was 
      diagnostic. The only significant predictor of phenotypic abnormality in the group 
      as a whole was the localization of one or both breakpoints to an R-positive 
      (G-negative) band with estimated predictive values of 0.69 (95% CL 0.54-0.81) and 
      0.90 (95% CL 0.60-0.98), respectively. R-positive bands are known to contain more 
      genes and have a higher guanine-cytosine (GC) content than do G-positive 
      (R-negative) bands; however, whether a gene was interrupted by the breakpoint or 
      the GC content in the 200 kB around the breakpoint had no discriminant ability. 
      Our results suggest that the large-scale genomic context of the breakpoint has 
      prognostic utility and that the pathological mechanism of mapping to an R-band 
      cannot be accounted for by direct gene inactivation.
FAU - Fantes, J A
AU  - Fantes JA
AD  - Medical and Developmental Genetics Section, Medical Research Council (MRC), Human 
      Genetics Unit, Edinburgh EH4 2XU, Scotland, UK.
FAU - Boland, E
AU  - Boland E
FAU - Ramsay, J
AU  - Ramsay J
FAU - Donnai, D
AU  - Donnai D
FAU - Splitt, M
AU  - Splitt M
FAU - Goodship, J A
AU  - Goodship JA
FAU - Stewart, H
AU  - Stewart H
FAU - Whiteford, M
AU  - Whiteford M
FAU - Gautier, P
AU  - Gautier P
FAU - Harewood, L
AU  - Harewood L
FAU - Holloway, S
AU  - Holloway S
FAU - Sharkey, F
AU  - Sharkey F
FAU - Maher, E
AU  - Maher E
FAU - van Heyningen, V
AU  - van Heyningen V
FAU - Clayton-Smith, J
AU  - Clayton-Smith J
FAU - Fitzpatrick, D R
AU  - Fitzpatrick DR
FAU - Black, G C M
AU  - Black GC
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - MC_U127527199/MRC_/Medical Research Council/United Kingdom
GR  - MC_U127561093/MRC_/Medical Research Council/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080327
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
SB  - IM
EIN - Am J Hum Genet. 2008 Apr;82(4):1019
MH  - Case-Control Studies
MH  - *Chromosome Aberrations
MH  - *Chromosome Mapping
MH  - Genetic Diseases, Inborn/*diagnosis
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Phenotype
MH  - Prognosis
MH  - Sequence Deletion
PMC - PMC2491339
EDAT- 2008/04/01 09:00
MHDA- 2008/05/14 09:00
PMCR- 2008/10/11
CRDT- 2008/04/01 09:00
PHST- 2007/11/19 00:00 [received]
PHST- 2008/02/03 00:00 [revised]
PHST- 2008/02/05 00:00 [accepted]
PHST- 2008/04/01 09:00 [pubmed]
PHST- 2008/05/14 09:00 [medline]
PHST- 2008/04/01 09:00 [entrez]
PHST- 2008/10/11 00:00 [pmc-release]
AID - S0002-9297(08)00161-4 [pii]
AID - AJHG100 [pii]
AID - 10.1016/j.ajhg.2008.02.007 [doi]
PST - ppublish
SO  - Am J Hum Genet. 2008 Apr;82(4):916-26. doi: 10.1016/j.ajhg.2008.02.007. Epub 2008 
      Mar 27.