TY - JOUR
T1 - Low-copy repeats mediate the common 3-Mb deletion in patients with velo- cardio-facial syndrome
AU - Edelmann, Lisa
AU - Pandita, Raj K.
AU - Morrow, Bernice E.
N1 - Funding Information:
We thank Drs. Raju Kucherlapati, Arthur Skoultchi, Anne Puech, Bruno Saint-Jore, and Steven Somlo for their helpful suggestions. We are grateful to Christine Carlson for her technical assistance in the initial stages of this project. B.E.M. is supported by National Institutes of Health (NIH) grant PO-1 HD 34980-01, an NARSAD Award (1996–98), an American Heart Association Grant-in-Aid, an American Heart Association Investigatorship Award, and March of Dimes grant FY98-0414. L.E. is supported by NIH grant T32 CA09060.
PY - 1999
Y1 - 1999
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=0033358588&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033358588&partnerID=8YFLogxK
U2 - 10.1086/302343
DO - 10.1086/302343
M3 - Article
C2 - 10090893
AN - SCOPUS:0033358588
SN - 0002-9297
VL - 64
SP - 1076
EP - 1086
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 4
ER -