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
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.