A physical and transcript map based upon refinement of the critical interval for PPH1, a gene for familial primary pulmonary hypertension

Citation
Rd. Machado et al., A physical and transcript map based upon refinement of the critical interval for PPH1, a gene for familial primary pulmonary hypertension, GENOMICS, 68(2), 2000, pp. 220-228
Citations number
41
Categorie Soggetti
Molecular Biology & Genetics
Journal title
GENOMICS
ISSN journal
08887543 → ACNP
Volume
68
Issue
2
Year of publication
2000
Pages
220 - 228
Database
ISI
SICI code
0888-7543(20000901)68:2<220:APATMB>2.0.ZU;2-X
Abstract
Primary pulmonary hypertension (PPH), an often fatal disorder, is character ized by sustained elevation of pulmonary artery pressure of unknown cause. In its familial form (FPPH), the disorder segregates as an autosomal domina nt 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 ar tificial chromosome (BAC)/P1 artificial chromosome contig (PAC), assembled by STS content mapping, across a newly identified minimum nonrecombinant in terval containing the gene designated PPH1. The physical map has served to establish polymorphic marker order unequivocally, enabling the establishmen t of detailed haplotypes for the region. Together with the identification o f novel recombination events in affected individuals from six newly ascerta ined kindreds, these data have allowed the significant reduction of the min imum PPH1 critical interval to a 4.8-cM region. The region, flanked by the polymorphic markers D2S115 (centromeric) and D2S1384 (telomeric), correspon ds to a minimum physical distance of 5.8 Mb at 2q33. Numerous expressed seq uence tags and known genes were placed on the YAC/BAC contig spanning the P PH1 gene critical region. (C) 2000 Academic Press.