PMID- 10699172
OWN - NLM
STAT- MEDLINE
DCOM- 20000414
LR  - 20220409
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 9
IP  - 4
DP  - 2000 Mar 1
TI  - Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: 
      genomic organization and deletion endpoint analysis.
PG  - 489-501
AB  - The 22q11.2 deletion syndrome, which includes DiGeorge and velocardiofacial 
      syndromes (DGS/VCFS), is the most common microdeletion syndrome. The majority of 
      deleted patients share a common 3 Mb hemizygous deletion of 22q11.2. The 
      remaining patients include those who have smaller deletions that are nested 
      within the 3 Mb typically deleted region (TDR) and a few with rare deletions that 
      have no overlap with the TDR. The identification of chromosome 22-specific 
      duplicated sequences or low copy repeats (LCRs) near the end-points of the 3 Mb 
      TDR has led to the hypothesis that they mediate deletions of 22q11.2. The entire 
      3 Mb TDR has been sequenced, permitting detailed investigation of the LCRs and 
      their involvement in the 22q11.2 deletions. Sequence analysis has identified four 
      LCRs within the 3 Mb TDR. Although the LCRs differ in content and organization of 
      shared modules, those modules that are common between them share 97-98% sequence 
      identity with one another. By fluorescence in situ hybridization (FISH) analysis, 
      the end-points of four variant 22q11.2 deletions appear to localize to the LCRs. 
      Pulsed-field gel electrophoresis and Southern hybridization have been used to 
      identify rearranged junction fragments from three variant deletions. Analysis of 
      junction fragments by PCR and sequencing of the PCR products implicate the LCRs 
      directly in the formation of 22q11.2 deletions. The evolutionary origin of the 
      duplications on chromosome 22 has been assessed by FISH analysis of non-human 
      primates. Multiple signals in Old World monkeys suggest that the duplication 
      events may have occurred at least 20-25 million years ago.
FAU - Shaikh, T H
AU  - Shaikh TH
AD  - Division of Human Genetics and Molecular Biology, The Children's Hospital of 
      Philadelphia, Philadelphia, PA 19104, USA.
FAU - Kurahashi, H
AU  - Kurahashi H
FAU - Saitta, S C
AU  - Saitta SC
FAU - O'Hare, A M
AU  - O'Hare AM
FAU - Hu, P
AU  - Hu P
FAU - Roe, B A
AU  - Roe BA
FAU - Driscoll, D A
AU  - Driscoll DA
FAU - McDonald-McGinn, D M
AU  - McDonald-McGinn DM
FAU - Zackai, E H
AU  - Zackai EH
FAU - Budarf, M L
AU  - Budarf ML
FAU - Emanuel, B S
AU  - Emanuel BS
LA  - eng
GR  - CA39926/CA/NCI NIH HHS/United States
GR  - DC02027/DC/NIDCD NIH HHS/United States
GR  - HD26979/HD/NICHD NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
SB  - IM
MH  - Animals
MH  - *Chromosome Deletion
MH  - Chromosomes, Human, Pair 22/*genetics
MH  - Contig Mapping
MH  - Gene Amplification
MH  - Gene Dosage
MH  - *Gene Duplication
MH  - Gorilla gorilla
MH  - Humans
MH  - Macaca mulatta
MH  - Pan paniscus
MH  - Sequence Analysis, DNA
MH  - Syndrome
EDAT- 2000/03/04 09:00
MHDA- 2000/04/25 09:00
CRDT- 2000/03/04 09:00
PHST- 2000/03/04 09:00 [pubmed]
PHST- 2000/04/25 09:00 [medline]
PHST- 2000/03/04 09:00 [entrez]
AID - ddd064 [pii]
AID - 10.1093/hmg/9.4.489 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2000 Mar 1;9(4):489-501. doi: 10.1093/hmg/9.4.489.