title: Complete and overlapping congenics proving the existence of a quantitative trait locus for blood pressure on Dahl rat chromosome 17.
abstract: Linkage studies suggested that a quantitative trait locus (QTL) for blood pressure (BP) was present in a region on chromosome 17 (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 localization of a QTL by linkage followed by the use of a congenic strain made with an incomplete chromosome coverage. To resolve this issue, we constructed five 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 approximately 15 cM 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 thorough chromosome coverage, the necessity for a genome-wide screening, and the use of "negative" controls in physically mapping a QTL by congenic strains.
authors.affiliation: Research Centre, Centre Hospitalier de l'Universite de Montréal (CHUM), Montréal, Québec, Canada.
authors.forename: Myrian
authors.initials: M
authors.lastname: Grondin
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Eliopoulos
authors.forename: Raphaelle
authors.initials: R
authors.lastname: Lambert
authors.forename: Yishu
authors.initials: Y
authors.lastname: Deng
authors.forename: Anita
authors.initials: A
authors.lastname: Ariyarajah
authors.forename: Myriam
authors.initials: M
authors.lastname: Moujahidine
authors.forename: Julie
authors.initials: J
authors.lastname: Dutil
authors.forename: Sophie
authors.initials: S
authors.lastname: Charron
authors.forename: Alan Y
authors.initials: AY
authors.lastname: Deng
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure / Q000235:genetics*; D002874:Chromosome Mapping; D002875:Chromosomes / Q000648:ultrastructure; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D016678:Genome; D006720:Homozygote; D006973:Hypertension / Q000235:genetics*; D008126:Lod Score; D008957:Models, Genetic; D015233:Models, Statistical; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D051381:Rats; D020303:Rats, Inbred Dahl
chemical_list: D005819:Genetic Markers