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Positional mapping of a rat blood pressure QTL to a congenic segment spanning <82kb with no rat gene predictions
Author(s) -
Joe Bina,
Gopalakrishnan Kathirvel,
Saikumar Jagannath,
Toland Edward J,
Farms Phyllis,
YergaWoolwine Shane,
Thangavel Jayakumar,
Kumarasamy Sivarajan
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.792.2
Subject(s) - congenic , quantitative trait locus , biology , genetics , locus (genetics) , gene , genomic dna , chromosome , candidate gene , allele , chromosome 4 , chromosomal region , bacterial artificial chromosome , genome
Genome‐wide association studies in humans suggest that a large number of alleles, each without a major effect, contribute to the genetics of blood pressure (BP). Our laboratory is focused on establishing a cause‐effect relationship between alleles and BP using rat genetic models of hypertension. Previously, a BP quantitative trait locus (QTL) was mapped within a congenic strain of the Dahl salt‐sensitive (S) rat containing 1.41Mb of rat chromosome 9 (RNO9) introgressed from the Dahl salt‐resistant (R) rat. High resolution mapping was conducted with this congenic strain as the progenitor. Eleven substrains with introgressed segments from 81.8kb to 1.33Mb were developed and tested for BP. The congenic strain with the shortest introgressed segment, S.R(9)INHx3x2Bx1x8 spanning 81.8kb had a significant BP lowering effect (−25, p<0.001) compared to the S rat. The BP of S.R(9)INHx3x2Bx1x8 was further confirmed by both telemetry and tail‐cuff methods. The mean survival of S.R(9)INHx3x2Bx1x8 congenic rats was longer than that of the S by 44 days. Sequencing of the 81.8kb region revealed 371 DNA variants. The 81.8kb segment does not contain any known rat genes. The critical region contains 658bp which is 99.39% identical to a genomic segment on rat chromosome 2 and contains 4 SNPs. Transcripts and proteins encoded by the gene Tns1 located at the 3′ end of this genomic segment on RNO9 and the gene Nup155 located at the 3′ end of the identical genomic segment on RNO2 were both expressed lower in S compared to S.R(INHx3x2Bx1x8). This data suggests that a common regulatory element of Tns1 and Nup155 located within S.R (INHx3x2Bx1x8) could be a candidate BP QTL.