PMID- 10090893
OWN - NLM
STAT- MEDLINE
DCOM- 20000405
LR  - 20190515
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 64
IP  - 4
DP  - 1999 Apr
TI  - Low-copy repeats mediate the common 3-Mb deletion in patients with
      velo-cardio-facial syndrome.
PG  - 1076-86
AB  - Velo-cardio-facial syndrome (VCFS) is the most common microdeletion syndrome in
      humans. It occurs with an estimated frequency of 1 in 4, 000 live births. Most
      cases occur sporadically, indicating that the deletion is recurrent in the
      population. More than 90% of patients with VCFS and a 22q11 deletion have a
      similar 3-Mb hemizygous deletion, suggesting that sequences at the breakpoints
      confer susceptibility to rearrangements. To define the region containing the
      chromosome breakpoints, we constructed an 8-kb-resolution physical map. We
      identified a low-copy repeat in the vicinity of both breakpoints. A set of
      genetic markers were integrated into the physical map to determine whether the
      deletions occur within the repeat. Haplotype analysis with genetic markers that
      flank the repeats showed that most patients with VCFS had deletion breakpoints in
      the repeat. Within the repeat is a 200-kb duplication of sequences, including a
      tandem repeat of genes/pseudogenes, surrounding the breakpoints. The genes in the
      repeat are GGT, BCRL, V7-rel, POM121-like, and GGT-rel. Physical mapping and
      genomic fingerprint analysis showed that the repeats are virtually identical in
      the 200-kb region, suggesting that the deletion is mediated by homologous
      recombination. Examination of two three-generation families showed that meiotic
      intrachromosomal recombination mediated the deletion.
FAU - Edelmann, L
AU  - Edelmann L
AD  - Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New
      York 10461, USA.
FAU - Pandita, R K
AU  - Pandita RK
FAU - Morrow, B E
AU  - Morrow BE
LA  - eng
GR  - P0-1 HD 34980-01/HD/NICHD NIH HHS/United States
GR  - T32 CA09060/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Genetic Markers)
SB  - IM
MH  - Abnormalities, Multiple/*genetics
MH  - Base Sequence
MH  - Chromosome Breakage/*genetics
MH  - *Chromosome Deletion
MH  - Chromosomes, Human, Pair 22/*genetics
MH  - DNA Fingerprinting
MH  - DiGeorge Syndrome/genetics
MH  - Female
MH  - Genetic Markers/genetics
MH  - Genetic Predisposition to Disease
MH  - Haplotypes/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Multigene Family/genetics
MH  - Pedigree
MH  - Physical Chromosome Mapping
MH  - Pseudogenes/genetics
MH  - Recombination, Genetic/*genetics
MH  - Repetitive Sequences, Nucleic Acid/*genetics
MH  - Sequence Homology, Nucleic Acid
MH  - Syndrome
PMC - PMC1377832
EDAT- 1999/03/26 03:02
MHDA- 2001/07/04 10:01
CRDT- 1999/03/26 03:02
PHST- 1999/03/26 03:02 [pubmed]
PHST- 2001/07/04 10:01 [medline]
PHST- 1999/03/26 03:02 [entrez]
AID - AJHG981003 [pii]
AID - 10.1086/302343 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Apr;64(4):1076-86. doi: 10.1086/302343.