Journal article
Searching for genes for cleft lip and/or palate based on breakpoint analysis of a balanced translocation t(9;17)(q32;q12)
The Cleft palate-craniofacial journal, Vol.46(5), pp.532-540
09/2009
DOI: 10.1597/08-047.1
PMCID: PMC2945731
PMID: 19929093
Abstract
Identification of the breakpoints of disease-associated chromosome rearrangements can provide informative clues to a positional cloning approach for genes responsible for inherited diseases. Recently, we found a three-generation Japanese family segregating balanced chromosome translocation t(9;17)(q32;q12). One of the subjects had cleft lip and palate. We examined whether regions near the breakpoint could be associated with cleft lip and/or palate.
We determined the breakpoints involved in the translocation by fluorescence in situ hybridization analysis and subsequent long-range polymerase chain reaction. In order to study the role of these disrupted regions in nonsyndromic cleft lip and/or palate, we performed mutation analysis and a haplotype-based transmission disequilibrium test using tagging single-nucleotide polymorphisms in the flanking regions of the breakpoints in white and Filipino nonsyndromic cleft lip and/or palate populations.
Sequence analysis demonstrated that two genes, SLC31A1 (solute carrier family 31 member 1) on chromosome 9 and CCL2 (chemokine ligand 2) on chromosome 17, were rearranged with the breaks occurring within their introns. It is interesting that SLC31A1 lies closed to BSPRY (B-box and SPRY domain), which is a candidate for involvement with cleft lip and/or palate. Some of the variants in BSPRY and CCL2 showed significant p values in the cleft lip and/or palate population compared with the control population. There was also statistically significant evidence of transmission distortion for haplotypes on both chromosomes 9 and 17.
The data support previous reports that genes on chromosomal regions of 9q and 17q play an important role in facial development.
Details
- Title: Subtitle
- Searching for genes for cleft lip and/or palate based on breakpoint analysis of a balanced translocation t(9;17)(q32;q12)
- Creators
- Junichiro Machida - Department of Maxillofacial Surgery, Aichi-Gakuin University, Nagoya, Japan. jmachida@dpc.aichi-gakuin.ac.jpTêmis M FélixJeffrey C MurrayKoh-ichiro YoshiuraMitsuyo TanemuraMunefumi KamamotoKazuo ShimozatoShin-ichi SontaTakao Ono
- Resource Type
- Journal article
- Publication Details
- The Cleft palate-craniofacial journal, Vol.46(5), pp.532-540
- DOI
- 10.1597/08-047.1
- PMID
- 19929093
- PMCID
- PMC2945731
- NLM abbreviation
- Cleft Palate Craniofac J
- ISSN
- 1055-6656
- eISSN
- 1545-1569
- Publisher
- SAGE Publications; United States
- Grant note
- P50 DE016215-01 / NIDCR NIH HHS P50 DE016215 / NIDCR NIH HHS R37 DE008559-18 / NIDCR NIH HHS R01 DE008559 / NIDCR NIH HHS R37 DE008559 / NIDCR NIH HHS DE016215 / NIDCR NIH HHS DE08559 / NIDCR NIH HHS R37 DE008559-17 / NIDCR NIH HHS
- Language
- English
- Date published
- 09/2009
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025466302771
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