Physiol. Genomics Journal of Applied Physiology
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Physiol. Genomics (January 4, 2005). doi:10.1152/physiolgenomics.00275.2004
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Submitted on November 18, 2004
Accepted on December 18, 2004

Complete and overlapping congenics proving the existence of a quantitative trait locus for blood pressure on Dahl rat Chromosome 17

Myrian Grondin1, Vasiliki Eliopoulos1, Raphaelle Lambert1, Yishu Deng2, Anita Ariyarajah1, Myriam Moujahidine1, Julie Dutil1, Sophie Charron1, and Alan Y Deng1*

1 Research Centre-CHUM, Montreal, Quebec, Canada
2 # 3 Peoples Hospital of Yunnan, Kunming, Yunnan, China

* To whom correspondence should be addressed. E-mail: alan.deng{at}umontreal.ca.

Linkage studies suggested that a quantitative trait locus (QTL) for blood pressure (BP) was present in a region on Chromosome (Chr) 17 of Dahl salt-sensitive (DSS) rats. A subsequent congenic strain targeting this QTL, however, could not confirm it. These conflicting results called into question the validity of localising a QTL by linkage followed by the use of congenic strain made with an incomplete chromosome coverage. To resolve this issue, we constructed 5 new congenic strains, designated C17S.L1 to C17S.L5, that completely spanned the ± 2 LOD confidence interval supposedly containing the QTL. Each congenic strain was made by replacing a segment of the DSS rat by that of the normotensive Lewis (LEW) rat. The only section to be LL homozygous is the region on Chr 17 specified in a congenic strain as evidenced by a total genome scan. The results showed that BPs of C17S.L1 and C17S.L2 were lower (p< 0.04) than that of DSS rats. In contrast, BPs of C17S.L3, C17S.L4 and C17S.L5 were not different (p>0.6) from that of DSS rats. Consequently a BP QTL must be located in an interval of about 15 centiMorgans shared between C17S.L1 and C17S.L2 and unique to them both, as opposed to C17S.L3, C17S.L4 and C17S.L5. The present study illustrates the importance of a thorough chromosome coverage, the necessity for a genome wide screening, and the use of 'negative' controls in physically mapping a QTL by congenic strains.




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