Applicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2.
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...
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| Format: | Conference item |
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2000
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| _version_ | 1797065027114500096 |
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| author | Jeffs, B Negrin, C Graham, D Clark, J Anderson, N Gauguier, D Dominiczak, A |
| author_facet | Jeffs, B Negrin, C Graham, D Clark, J Anderson, N Gauguier, D Dominiczak, A |
| author_sort | Jeffs, B |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T21:22:45Z |
| format | Conference item |
| id | oxford-uuid:42076546-11b6-482d-9212-9d0f2c3b7af3 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T21:22:45Z |
| publishDate | 2000 |
| record_format | dspace |
| spelling | oxford-uuid:42076546-11b6-482d-9212-9d0f2c3b7af32022-03-26T14:47:06ZApplicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2.Conference itemhttp://purl.org/coar/resource_type/c_5794uuid:42076546-11b6-482d-9212-9d0f2c3b7af3Symplectic Elements at Oxford2000Jeffs, BNegrin, CGraham, DClark, JAnderson, NGauguier, DDominiczak, AThe 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. |
| spellingShingle | Jeffs, B Negrin, C Graham, D Clark, J Anderson, N Gauguier, D Dominiczak, A Applicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2. |
| title | Applicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2. |
| title_full | Applicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2. |
| title_fullStr | Applicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2. |
| title_full_unstemmed | Applicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2. |
| title_short | Applicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2. |
| title_sort | applicability of a speed congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2 |
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