RGD Reference Report - Isolation and high-throughput sequencing of two closely linked epistatic hypertension susceptibility loci with a panel of bicongenic strains. - Rat Genome Database

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Isolation and high-throughput sequencing of two closely linked epistatic hypertension susceptibility loci with a panel of bicongenic strains.

Authors: Pillai, R  Waghulde, H  Nie, Y  Gopalakrishnan, K  Kumarasamy, S  Farms, P  Garrett, MR  Atanur, SS  Maratou, K  Aitman, TJ  Joe, B 
Citation: Pillai R, etal., Physiol Genomics. 2013 Aug 15;45(16):729-36. doi: 10.1152/physiolgenomics.00077.2013. Epub 2013 Jun 11.
RGD ID: 7495753
Pubmed: PMID:23757393   (View Abstract at PubMed)
PMCID: PMC3742915   (View Article at PubMed Central)
DOI: DOI:10.1152/physiolgenomics.00077.2013   (Journal Full-text)

Interactions or epistasis between genetic factors may contribute to "missing heritability." While linkage analyses detect epistasis, defining the limits of the interacting segments poses a significant challenge especially when the interactions are between loci in close proximity. The goal of the present study was to isolate two such epistatic blood pressure (BP) loci on rat chromosome 5. A panel of S.LEW bicongenic strains along with the corresponding monocongenic strains was constructed. BP of each set comprising of one bicongenic and two corresponding monocongenic strains were determined along with the parental Salt-sensitive (S) strain. Epistasis was observed in one out of four sets of congenic strains, wherein systolic blood pressures (SBP) of the two monocongenic strains S.LEW(5)x6Bx9x5a and S.LEW(5)x6Bx9x5b were comparable to that of S, but the SBP of the bicongenic strain S.LEW(5)x6Bx9x5 (157 +/- 4.3 mmHg) was significantly lower than that of S (196 +/- 6.8 mmHg, P < 0.001). A two-way ANOVA indicated significant interactions between the LEW alleles at the two loci. The interacting loci were 2.02 Mb apart and located within genomic segments spanning 7.77 and 4.18 Mb containing 7,360 and 2,753 candidate variants, respectively. The current study demonstrates definitive evidence for epistasis and provides genetic tools for further dissection of the isolated epistatic BP loci.




Objects Annotated

QTLs
Bp372  (Blood pressure QTL 372)
Bp373  (Blood pressure QTL 373)

Objects referenced in this article
Marker D5Mco48 D5Mco48 Rattus norvegicus
Marker D5Mco49 D5Mco49 Rattus norvegicus
Marker D5Mco50 D5Mco50 Rattus norvegicus
Marker D5Mco51 D5Mco51 Rattus norvegicus
Marker D5Mco52 D5Mco52 Rattus norvegicus
Marker D5Mco55 D5Mco55 Rattus norvegicus
Marker D5Mco56 D5Mco56 Rattus norvegicus
Marker D5Mco57 D5Mco57 Rattus norvegicus
Marker D5Mco58 D5Mco58 Rattus norvegicus
Marker D5Mco39 D5Mco39 Rattus norvegicus
Marker D5Mco40 D5Mco40 Rattus norvegicus
Marker D5Mco41 D5Mco41 Rattus norvegicus
Marker D5Mco42 D5Mco42 Rattus norvegicus
Marker D5Mco43 D5Mco43 Rattus norvegicus
Marker D5Mco44 D5Mco44 Rattus norvegicus
Marker D5Mco45 D5Mco45 Rattus norvegicus
Marker D5Mco46 D5Mco46 Rattus norvegicus
Marker D5Mco47 D5Mco47 Rattus norvegicus
QTL Bp156 Blood pressure QTL 156 Rattus norvegicus
QTL Bp157 Blood pressure QTL 157 Rattus norvegicus
Strain SS.LEW-(D5Mco39-D5Mco57)(D5Mco41-D5Mco47)/Mco null Rattus norvegicus
Strain SS.LEW-(D5Mco39-D5Mco57)(D5Mco42-D5Mco47)/Mco null Rattus norvegicus
Strain SS.LEW-(D5Mco39-D5Mco57)(D5Mco43-D5Mco47)/Mco null Rattus norvegicus
Strain SS.LEW-(D5Mco39-D5Mco57)/1Mco null Rattus norvegicus
Strain SS.LEW-(D5Mco39-D5Mco57)/2Mco null Rattus norvegicus
Strain SS.LEW-(D5Mco39-D5Mco57)/3Mco null Rattus norvegicus
Strain SS.LEW-(D5Mco41-D5Mco47)/Mco null Rattus norvegicus
Strain SS.LEW-(D5Mco42-D5Mco47)/1Mco null Rattus norvegicus
Strain SS.LEW-(D5Mco43-D5Mco47)/Mco null Rattus norvegicus

Additional Information