Searching for genes for cleft lip and/or palate based on breakpoint analysis of a balanced translocation t(9;17)(q32;q12).
Cleft Palate Craniofac J
; 46(5): 532-40, 2009 Sep.
Article
en En
| MEDLINE
| ID: mdl-19929093
ABSTRACT
OBJECTIVE:
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.METHODS:
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.RESULTS:
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.CONCLUSIONS:
The data support previous reports that genes on chromosomal regions of 9q and 17q play an important role in facial development.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Translocación Genética
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Cromosomas Humanos Par 9
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Cromosomas Humanos Par 17
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Labio Leporino
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Fisura del Paladar
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Rotura Cromosómica
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Puntos de Rotura del Cromosoma
Tipo de estudio:
Prognostic_studies
Límite:
Humans
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Male
/
Newborn
Idioma:
En
Revista:
Cleft Palate Craniofac J
Asunto de la revista:
ODONTOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Japón