title: Fine mapping of PPH1, a gene for familial primary pulmonary hypertension, to a 3-cM region on chromosome 2q33.
abstract: Familial primary pulmonary hypertension (PPH) is a rare autosomal dominant disease characterized by distinctive changes in pulmonary arterioles that lead to increased pulmonary artery pressures, right ventricular failure, and death. Our previous studies had mapped the disease locus, PPH1, to a 27-cM region on chromosome 2q31-q33, with a maximum multipoint logarithm of the odds favoring genetic linkage score of 3.87 with markers D2S350 and D2S364. To narrow the minimal genetic region for PPH, we physically mapped 33 highly polymorphic microsatellite markers and used them to genotype 44 affected individuals and 133 unaffected individuals from 17 families with PPH. We observed recombination events that substantially reduced the interval for PPH1 to the approximately 3-cM region that separates D2S311 and D2S1384. This entire region lies within chromosome 2q33. A maximum two-point lod score of 7.23 at a recombination fraction of zero was obtained for marker D2S307. A maximum multipoint lod score of 7.41 was observed close to marker D2S1367. The current minimal genetic region contains multiple candidate genes for PPH, including a locus thought to play a role in lung cancer.
authors.affiliation: Department of Genetics and Development, Columbia Genome Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Deng
authors.forename: F
authors.initials: F
authors.lastname: Haghighi
authors.forename: L
authors.initials: L
authors.lastname: Helleby
authors.forename: K
authors.initials: K
authors.lastname: Vanterpool
authors.forename: E M
authors.initials: EM
authors.lastname: Horn
authors.forename: R J
authors.initials: RJ
authors.lastname: Barst
authors.forename: S E
authors.initials: SE
authors.lastname: Hodge
authors.forename: J H
authors.initials: JH
authors.lastname: Morse
authors.forename: J A
authors.initials: JA
authors.lastname: Knowles
mesh_terms: D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D010375:Pedigree
chemical_list: D005819:Genetic Markers