Dissection of a quantitative trait locus for genetic hypertension on rat chromosome 10
| Autor: | G.M. Lathrop, Dominique Gauguier, Reinhold Kreutz, Norbert Hubner, Klaus Lindpaintner, Detlev Ganten, M. T. Bihoreau, Michael R. James |
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| Rok vydání: | 1995 |
| Předmět: |
Genetic Markers
Male Genotype Genetic Linkage Molecular Sequence Data Population Congenic Locus (genetics) Quantitative trait locus Biology Rats Inbred WKY Spontaneously hypertensive rat Genetic linkage Rats Inbred SHR Animals Selection Genetic education Gene Crosses Genetic Genetics education.field_of_study Multidisciplinary Base Sequence Chromosome Mapping Chromosome Molecular biology Rats Meiosis Phenotype Hypertension Female Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 92:8778-8782 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.92.19.8778 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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