title: 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.
abstract: 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.
authors.affiliation: University Children's Hospital Freiburg, Freiburg; University Hospital for Ear, Nose and Throat, Freiburg, Germany. omran@kkl200.ukl.uni-freiburg.de
authors.forename: H
authors.initials: H
authors.lastname: Omran
authors.forename: K
authors.initials: K
authors.lastname: Häffner
authors.forename: A
authors.initials: A
authors.lastname: Völkel
authors.forename: J
authors.initials: J
authors.lastname: Kuehr
authors.forename: U P
authors.initials: UP
authors.lastname: Ketelsen
authors.forename: U H
authors.initials: UH
authors.lastname: Ross
authors.forename: N
authors.initials: N
authors.lastname: Konietzko
authors.forename: T
authors.initials: T
authors.lastname: Wienker
authors.forename: M
authors.initials: M
authors.lastname: Brandis
authors.forename: F
authors.initials: F
authors.lastname: Hildebrandt
mesh_terms: D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D002925:Ciliary Motility Disorders / Q000235:genetics*; D004398:Dyneins / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D016415:Sequence Alignment
chemical_list: D005819:Genetic Markers; D004398:Dyneins