title: A physical and transcript map based upon refinement of the critical interval for PPH1, a gene for familial primary pulmonary hypertension. The International PPH Consortium.
abstract: Primary pulmonary hypertension (PPH), an often fatal disorder, is characterized by sustained elevation of pulmonary artery pressure of unknown cause. In its familial form (FPPH), the disorder segregates as an autosomal dominant and displays markedly reduced penetrance. A gene for FPPH was previously localized to a 25-cM interval on the long arm of chromosome 2 (2q31-q33). We now report a complete yeast artificial chromosome (YAC) and bacterial artificial chromosome (BAC)/P1 artificial chromosome contig (PAC), assembled by STS content mapping, across a newly identified minimum nonrecombinant interval containing the gene designated PPH1. The physical map has served to establish polymorphic marker order unequivocally, enabling the establishment of detailed haplotypes for the region. Together with the identification of novel recombination events in affected individuals from six newly ascertained kindreds, these data have allowed the significant reduction of the minimum PPH1 critical interval to a 4.8-cM region. The region, flanked by the polymorphic markers D2S115 (centromeric) and D2S1384 (telomeric), corresponds to a minimum physical distance of 5.8 Mb at 2q33. Numerous expressed sequence tags and known genes were placed on the YAC/BAC contig spanning the PPH1 gene critical region.
authors.affiliation: Division of Medical Genetics, University of Leicester, Leicester, LE1 7RH, England.
authors.forename: R D
authors.initials: RD
authors.lastname: Machado
authors.forename: M W
authors.initials: MW
authors.lastname: Pauciulo
authors.forename: N
authors.initials: N
authors.lastname: Fretwell
authors.forename: C
authors.initials: C
authors.lastname: Veal
authors.forename: J R
authors.initials: JR
authors.lastname: Thomson
authors.forename: C
authors.initials: C
authors.lastname: Vilariño Güell
authors.forename: M
authors.initials: M
authors.lastname: Aldred
authors.forename: C A
authors.initials: CA
authors.lastname: Brannon
authors.forename: R C
authors.initials: RC
authors.lastname: Trembath
authors.forename: W C
authors.initials: WC
authors.lastname: Nichols
mesh_terms: D017101:Bacteriophage P1 / Q000235:genetics; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002876:Chromosomes, Bacterial / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D020451:Contig Mapping; D004247:DNA / Q000235:genetics; D020224:Expressed Sequence Tags; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D020161:Physical Chromosome Mapping; D016324:Sequence Tagged Sites; D014158:Transcription, Genetic
chemical_list: D004247:DNA