Dissection of a quantitative trait locus for genetic hypertension on rat chromosome 10.
We have previously identified a locus on rat chromosome 10 as carrying a major hypertension gene, BP/SP-1. The 100:1 odds support interval for this gene extended over a 35-centimorgan (cM) region of the chromosome that included the angiotensin I-converting enzyme (ACE) locus as demonstrated in a cross between the stroke-prone spontaneously hypertensive rat (SHRSPHD) and the normotensive Wistar-Kyoto (WKY-0HD) rat. Here we report on the further characterization of BP/SP-1, using a congenic strain, WKY-1HD. WKY-1HD animals carry a 6-cM chromosomal fragment genotypically identical with SHRSPHD on chromosome 10, 26 cM away from the ACE locus. Higher blood pressures in the WKY-1HD strain compared with the WKY-0HD strain, as well as absence of linkage of the chromosome 10 region to blood pressure in an F2 (WKY-1HD x SHRSPHD) population suggested the existence of a quantitative trait locus, termed BP/SP-1a, that lies within the SHRSP-congenic region in WKY-1HD. Linkage analysis in the F2 (WKY-0HD x SHRSPHD) cross revealed that BP/SP-1a is linked to basal blood pressure, whereas a second locus on chromosome 10, termed BP/SP-1b, that maps closer to the ACE locus cosegregates predominantly with blood pressure after exposure to excess dietary NaCl. Thus, we hypothesize that the previously reported effect of BP/SP-1 represents a composite phenotype that can be dissected into at least two specific components on the basis of linkage data and congenic experimentation. One of the loci identified, BP/SP-1a, represents the most precisely mapped locus affecting blood pressure that has so far been characterized by random-marker genome screening.
Kreutz
R
R
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Hübner
N
N
James
M R
MR
Bihoreau
M T
MT
Gauguier
D
D
Lathrop
G M
GM
Ganten
D
D
Lindpaintner
K
K
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008540:Meiosis; D008969:Molecular Sequence Data; D010641:Phenotype; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012641:Selection, Genetic
D005819:Genetic Markers