Journal article
Analysis of two translocation breakpoints and identification of a negative regulatory element in patients with Rieger's syndrome
Birth defects research. A Clinical and molecular teratology, Vol.70(2), pp.82-91
2004
DOI: 10.1002/bdra.10154
PMID: 14991915
Abstract
BACKGROUND
Rieger's syndrome is an autosomal dominant disorder characterized by eye, tooth, and umbilical anomalies. A gene responsible for Rieger's syndrome, PITX2, has previously been cloned using two patients with balanced translocations, t(4;16) and t(4;11), with breakpoints that lie near the gene, but which do not interrupt it.
METHODS
We sequenced both breakpoint regions on chromosome 4 and screened this area for novel genes. Fluorescence in situ hybridization (FISH) was used to determine if PITX2 was still present on the 4:16 chromosome. Both the chromosome 16 and chromosome 11 breakpoints were cloned and sequenced using panhandle polymerase chain reaction (PHPCR). Transient transfection studies were performed to compare effects on a reporter gene between native chromosome 4 sequence and chromosome 11 sequence.
RESULTS
The region surrounding PITX2 on chromosome 4 is rich in repetitive elements, but no novel genes were identified. FISH demonstrated that PITX2 was intact on the 4:16 translocation chromosome. The PHPCR experiments demonstrated that the translocated regions of chromosomes 16 and 11 were repeat‐rich, and transfection studies revealed a slight enhancer effect with the chromosome 4 sequence, and a strong silencer effect when the chromosome 11 sequence was present.
CONCLUSIONS
Given the lack of any novel genes near either breakpoint, changes in potential regulatory elements may be the best model to explain the loss of PITX2 expression in these patients and hence the Rieger's syndrome phenotype.
Details
- Title: Subtitle
- Analysis of two translocation breakpoints and identification of a negative regulatory element in patients with Rieger's syndrome
- Creators
- Dimitri G TREMBATH - Department of Pediatrics, The University of Iowa, Iowa City, Iowa, United StatesElena V SEMINA - Department of Pediatrics, The University of Iowa, Iowa City, Iowa, United StatesDouglas H JONES - Department of Psychiatry, The University of Iowa, Iowa City, Iowa, United StatesShivanand R PATIL - Department of Pediatrics, The University of Iowa, Iowa City, Iowa, United StatesQining Qian - Department of Pediatrics, The University of Iowa, Iowa City, Iowa, United StatesBrad A AMENDT - Department of Biological Science, The University of Tulsa, Tulsa, Oklahoma, United StatesAndrew F RUSSO - Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa, United StatesJeffrey C MURRAY - Department of Pediatrics, The University of Iowa, Iowa City, Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Birth defects research. A Clinical and molecular teratology, Vol.70(2), pp.82-91
- DOI
- 10.1002/bdra.10154
- PMID
- 14991915
- NLM abbreviation
- Birth Defects Res A Clin Mol Teratol
- ISSN
- 1542-0752
- eISSN
- 1542-0760
- Publisher
- Wiley; Hoboken, NJ
- Language
- English
- Date published
- 2004
- Academic Unit
- Neurology; Orthodontics; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Iowa Neuroscience Institute; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984014018402771
Metrics
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