Homozygosity mapping of a gene locus for primary ciliary dyskinesia on chromosome 5p and identification of the heavy dynein chain DNAH5 as a candidate gene.
Am J Respir Cell Mol Biol
; 23(5): 696-702, 2000 Nov.
Article
en En
| MEDLINE
| ID: mdl-11062149
Reduced mucociliary clearance in primary ciliary dyskinesia (PCD) causes recurrent infections of the upper and lower respiratory tract. The disease is usually inherited as an autosomal recessive trait. To identify a gene locus for PCD, we studied a large consanguineous family of Arabic origin. Direct examination of the respiratory cilia revealed ciliary akinesia. Electron microscopic examination of cilia showed absence of the outer dynein arms. Two of four affected individuals exhibited a situs inversus, typical for Kartagener syndrome, due to randomization of the left/right body axis. A total genome scan with 340 highly polymorphic microsatellites was performed. We localized a new gene locus for PCD to a region of homozygosity by descent on chromosome 5p15-p14 with a parametric multipoint logarithm of odds ratio (LOD) score of Zmax = 3.51 flanked by markers D5S2095 and D5S502 within an interval of 20 centimorgans sex-averaged genetic distance. Applying a polymerase chain reaction-based approach, we identified a 1.5-kb partial complementary DNA of DNAH5 encoding a Chlamydomonas-related axonemal heavy dynein chain within the critical disease interval of this new PCD locus. On the basis of the Chlamydomonas model for PCD, this gene represents an excellent candidate for PCD.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cromosomas Humanos Par 5
/
Mapeo Cromosómico
/
Trastornos de la Motilidad Ciliar
/
Dineínas
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Am J Respir Cell Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2000
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Estados Unidos