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. 1996 Feb 1;97(3):777–788. doi: 10.1172/JCI118477

Genetic mapping of two blood pressure quantitative trait loci on rat chromosome 1.

L Gu 1, H Dene 1, A Y Deng 1, B Hoebee 1, M T Bihoreau 1, M James 1, J P Rapp 1
PMCID: PMC507116  PMID: 8609235

Abstract

A genetic map for rat chromosome 1 was constructed using 66 microsatellite markers typed on either or both of two populations derived from inbred Dahl salt-sensitive (S) rats: F2(LEW x S) n = 151, and F2(WKY x S) n = 159. These populations had been raised on a high salt (8% NaCl) diet. Systolic blood pressure and heart weight were found to be genetically linked to two separate regions on rat chromosome 1 in the F2(LEW x S) population. One region was centered around the anonymous SA locus and accounted for 24 mmHg of blood pressure. The other region was 55 cM from the SA locus centered around a cluster of cytochromes P450 loci, and accounted for 30 mmHg of blood pressure. Since blood pressure and heart weight were highly correlated these same regions were also linked to heart weight. These results were cross-specific as linkage of these chromosome 1 regions to blood pressure and heart weight was not observed in several other F2 populations derived by crossing S and other normotensive control strains. This is presumably due to different alleles and/or different genetic backgrounds in the various populations. The SA region of chromosome 1 was found to influence body weight in F2(LEW x S) rats. Combining the present data with our previously published data on the F2(LEW x S) population showed that four separate quantitative trait loci with additive effects accounted for 106 mmHg and 38% of the total variance of blood pressure and for 506 mg and 34% of the total variance of heart wt.

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Selected References

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  1. Blin N., Stafford D. W. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976 Sep;3(9):2303–2308. doi: 10.1093/nar/3.9.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buñag R. D., Butterfield J. Tail-cuff blood pressure measurement without external preheating in awake rats. Hypertension. 1982 Nov-Dec;4(6):898–903. doi: 10.1161/01.hyp.4.6.898. [DOI] [PubMed] [Google Scholar]
  3. Cicila G. T., Rapp J. P., Bloch K. D., Kurtz T. W., Pravenec M., Kren V., Hong C. C., Quertermous T., Ng S. C. Cosegregation of the endothelin-3 locus with blood pressure and relative heart weight in inbred Dahl rats. J Hypertens. 1994 Jun;12(6):643–651. [PubMed] [Google Scholar]
  4. Collins F. S. Positional cloning moves from perditional to traditional. Nat Genet. 1995 Apr;9(4):347–350. doi: 10.1038/ng0495-347. [DOI] [PubMed] [Google Scholar]
  5. Darvasi A., Weinreb A., Minke V., Weller J. I., Soller M. Detecting marker-QTL linkage and estimating QTL gene effect and map location using a saturated genetic map. Genetics. 1993 Jul;134(3):943–951. doi: 10.1093/genetics/134.3.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Deng A. Y., Dene H., Pravenec M., Rapp J. P. Genetic mapping of two new blood pressure quantitative trait loci in the rat by genotyping endothelin system genes. J Clin Invest. 1994 Jun;93(6):2701–2709. doi: 10.1172/JCI117284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Deng A. Y., Dene H., Rapp J. P. Mapping of a quantitative trait locus for blood pressure on rat chromosome 2. J Clin Invest. 1994 Jul;94(1):431–436. doi: 10.1172/JCI117341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deng A. Y., Rapp J. P. Locus for the inducible, but not a constitutive, nitric oxide synthase cosegregates with blood pressure in the Dahl salt-sensitive rat. J Clin Invest. 1995 May;95(5):2170–2177. doi: 10.1172/JCI117906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Deng Y., Rapp J. P. Cosegregation of blood pressure with angiotensin converting enzyme and atrial natriuretic peptide receptor genes using Dahl salt-sensitive rats. Nat Genet. 1992 Jul;1(4):267–272. doi: 10.1038/ng0792-267. [DOI] [PubMed] [Google Scholar]
  10. Goldmuntz E. A., Remmers E. F., Zha H., Cash J. M., Mathern P., Crofford L. J., Wilder R. L. Genetic map of 12 polymorphic loci on rat chromosome 1. Genomics. 1993 Jun;16(3):761–764. doi: 10.1006/geno.1993.1261. [DOI] [PubMed] [Google Scholar]
  11. Gu L., Dene H., Rapp J. P. Three microsatellites defining four alleles for the rat SA gene. Mamm Genome. 1994 Dec;5(12):833–833. doi: 10.1007/BF00292032. [DOI] [PubMed] [Google Scholar]
  12. Hansson J. H., Nelson-Williams C., Suzuki H., Schild L., Shimkets R., Lu Y., Canessa C., Iwasaki T., Rossier B., Lifton R. P. Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. Nat Genet. 1995 Sep;11(1):76–82. doi: 10.1038/ng0995-76. [DOI] [PubMed] [Google Scholar]
  13. Harris E. L., Dene H., Rapp J. P. SA gene and blood pressure cosegregation using Dahl salt-sensitive rats. Am J Hypertens. 1993 Apr;6(4):330–334. doi: 10.1093/ajh/6.4.330. [DOI] [PubMed] [Google Scholar]
  14. Hirt D. L., Jacobson H. R. Functional effects of cytochrome P450 arachidonate metabolites in the kidney. Semin Nephrol. 1991 Mar;11(2):148–155. [PubMed] [Google Scholar]
  15. Hoebee B., de Stoppelaar J. M., Suijkerbuijk R. F., Monard S. Isolation of rat chromosome-specific paint probes by bivariate flow sorting followed by degenerate oligonucleotide primed-PCR. Cytogenet Cell Genet. 1994;66(4):277–282. doi: 10.1159/000133712. [DOI] [PubMed] [Google Scholar]
  16. Iwai N., Inagami T. Identification of a candidate gene responsible for the high blood pressure of spontaneously hypertensive rats. J Hypertens. 1992 Oct;10(10):1155–1157. doi: 10.1097/00004872-199210000-00007. [DOI] [PubMed] [Google Scholar]
  17. Iwai N., Inagami T. Isolation of preferentially expressed genes in the kidneys of hypertensive rats. Hypertension. 1991 Feb;17(2):161–169. doi: 10.1161/01.hyp.17.2.161. [DOI] [PubMed] [Google Scholar]
  18. Iwai N., Ohmichi N., Hanai K., Nakamura Y., Kinoshita M. Human SA gene locus as a candidate locus for essential hypertension. Hypertension. 1994 Mar;23(3):375–380. doi: 10.1161/01.hyp.23.3.375. [DOI] [PubMed] [Google Scholar]
  19. Jacob H. J., Brown D. M., Bunker R. K., Daly M. J., Dzau V. J., Goodman A., Koike G., Kren V., Kurtz T., Lernmark A. A genetic linkage map of the laboratory rat, Rattus norvegicus. Nat Genet. 1995 Jan;9(1):63–69. doi: 10.1038/ng0195-63. [DOI] [PubMed] [Google Scholar]
  20. Kunieda T., Kobayashi E., Tachibana M., Ikadai H., Imamichi T. Polymorphic microsatellite loci of the rat (Rattus norvegicus). Mamm Genome. 1992;3(10):564–567. doi: 10.1007/BF00350622. [DOI] [PubMed] [Google Scholar]
  21. Lander E. S., Botstein D. Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics. 1989 Jan;121(1):185–199. doi: 10.1093/genetics/121.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lander E. S., Green P., Abrahamson J., Barlow A., Daly M. J., Lincoln S. E., Newberg L. A., Newburg L. MAPMAKER: an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations. Genomics. 1987 Oct;1(2):174–181. doi: 10.1016/0888-7543(87)90010-3. [DOI] [PubMed] [Google Scholar]
  23. Lander E. S., Schork N. J. Genetic dissection of complex traits. Science. 1994 Sep 30;265(5181):2037–2048. doi: 10.1126/science.8091226. [DOI] [PubMed] [Google Scholar]
  24. Lindpaintner K., Hilbert P., Ganten D., Nadal-Ginard B., Inagami T., Iwai N. Molecular genetics of the SA-gene: cosegregation with hypertension and mapping to rat chromosome 1. J Hypertens. 1993 Jan;11(1):19–23. doi: 10.1097/00004872-199301000-00004. [DOI] [PubMed] [Google Scholar]
  25. McGiff J. C. Cytochrome P-450 metabolism of arachidonic acid. Annu Rev Pharmacol Toxicol. 1991;31:339–369. doi: 10.1146/annurev.pa.31.040191.002011. [DOI] [PubMed] [Google Scholar]
  26. Nabika T., Bonnardeaux A., James M., Julier C., Jeunemaitre X., Corvol P., Lathrop M., Soubrier F. Evaluation of the SA locus in human hypertension. Hypertension. 1995 Jan;25(1):6–13. doi: 10.1161/01.hyp.25.1.6. [DOI] [PubMed] [Google Scholar]
  27. Rapp J. P., Dene H., Deng A. Y. Seven renin alleles in rats and their effects on blood pressure. J Hypertens. 1994 Apr;12(4):349–355. [PubMed] [Google Scholar]
  28. Rapp J. P., Dene H. Development and characteristics of inbred strains of Dahl salt-sensitive and salt-resistant rats. Hypertension. 1985 May-Jun;7(3 Pt 1):340–349. [PubMed] [Google Scholar]
  29. Rapp J. P., Deng A. Y. Detection and positional cloning of blood pressure quantitative trait loci: is it possible? Identifying the genes for genetic hypertension. Hypertension. 1995 Jun;25(6):1121–1128. doi: 10.1161/01.hyp.25.6.1121. [DOI] [PubMed] [Google Scholar]
  30. Samani N. J., Lodwick D., Vincent M., Dubay C., Kaiser M. A., Kelly M. P., Lo M., Harris J., Sassard J., Lathrop M. A gene differentially expressed in the kidney of the spontaneously hypertensive rat cosegregates with increased blood pressure. J Clin Invest. 1993 Aug;92(2):1099–1103. doi: 10.1172/JCI116616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Serikawa T., Kuramoto T., Hilbert P., Mori M., Yamada J., Dubay C. J., Lindpainter K., Ganten D., Guénet J. L., Lathrop G. M. Rat gene mapping using PCR-analyzed microsatellites. Genetics. 1992 Jul;131(3):701–721. doi: 10.1093/genetics/131.3.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shimkets R. A., Warnock D. G., Bositis C. M., Nelson-Williams C., Hansson J. H., Schambelan M., Gill J. R., Jr, Ulick S., Milora R. V., Findling J. W. Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell. 1994 Nov 4;79(3):407–414. doi: 10.1016/0092-8674(94)90250-x. [DOI] [PubMed] [Google Scholar]
  33. Szpirer C., Rivière M., Szpirer J., Levan G., Guo D. F., Iwai N., Inagami T. Chromosomal assignment of human and rat hypertension candidate genes: type 1 angiotensin II receptor genes and the SA gene. J Hypertens. 1993 Sep;11(9):919–925. doi: 10.1097/00004872-199309000-00005. [DOI] [PubMed] [Google Scholar]
  34. Tanksley S. D. Mapping polygenes. Annu Rev Genet. 1993;27:205–233. doi: 10.1146/annurev.ge.27.120193.001225. [DOI] [PubMed] [Google Scholar]
  35. Telenius H., Carter N. P., Bebb C. E., Nordenskjöld M., Ponder B. A., Tunnacliffe A. Degenerate oligonucleotide-primed PCR: general amplification of target DNA by a single degenerate primer. Genomics. 1992 Jul;13(3):718–725. doi: 10.1016/0888-7543(92)90147-k. [DOI] [PubMed] [Google Scholar]
  36. Telenius H., Pelmear A. H., Tunnacliffe A., Carter N. P., Behmel A., Ferguson-Smith M. A., Nordenskjöld M., Pfragner R., Ponder B. A. Cytogenetic analysis by chromosome painting using DOP-PCR amplified flow-sorted chromosomes. Genes Chromosomes Cancer. 1992 Apr;4(3):257–263. doi: 10.1002/gcc.2870040311. [DOI] [PubMed] [Google Scholar]

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