Applicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2

Hypertension. 2000 Jan;35(1 Pt 2):179-87. doi: 10.1161/01.hyp.35.1.179.

Abstract

The identification of any quantitative trait locus (QTL) via a genome scan is only the first step toward the ultimate goal of gene identification. The next step is the production of congenic strains by which the existence of a QTL may be verified and the implicated chromosomal region be reduced to a size applicable to positional cloning of the causal gene. We used a speed congenic breeding protocol previously verified in mice for 2 blood pressure QTLs on rat chromosome 2. Four congenic strains were produced through introgression of various segments of chromosome 2 from Wistar-Kyoto rats from Glasgow colonies [WKY((Gla)) rats] into the recipient stroke-prone spontaneously hypertensive rats from Glasgow colonies [SHRSP((Gla))], and vice versa. The number of backcross generations required for each strain to achieve complete homozygosity at 83 background genetic markers in a "best" male varied between 3 and 4. Transfer of the region of rat chromosome 2 containing both QTLs from WKY((Gla)) into an SHRSP((Gla)) genetic background lowered both baseline and salt-loaded systolic blood pressure by approximately 20 and approximately 40 mm Hg in male congenic rats compared with the SHRSP parental strain (F=53.4, P<0.005; F=28.0, P< 0.0005, respectively). In contrast, control animals for stowaway heterozygosity presented no deviation from the blood pressure values recorded for the SHRSP((Gla)), indicating that if such heterozygosity exists, its effect on blood pressure is negligible. A reciprocal strategy in which 1 or both QTLs on rat chromosome 2 were transferred from SHRSP((Gla)) into a WKY((Gla)) genetic background resulted in statistically significant but smaller blood pressure increases for 1 of these QTLs. These results confirm the existence of blood pressure QTLs on rat chromosome 2 and demonstrate the applicability of a speed congenic strategy in the rat and emphasize the important role of the genetic background.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / genetics*
  • Chromosome Mapping
  • Circadian Rhythm
  • DNA, Satellite / analysis
  • Female
  • Genetic Markers
  • Genotype
  • Homozygote
  • Hypertension / genetics*
  • Male
  • Quantitative Trait, Heritable*
  • Rats
  • Rats, Inbred SHR / genetics*
  • Rats, Inbred WKY
  • Species Specificity
  • Stroke / genetics

Substances

  • DNA, Satellite
  • Genetic Markers