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Alleles of a S.LEW congenic rat spanning 320.6kb further increases the BP of the hypertensive Dahl S rat: Evidence for Rffl and/or two miRNAs as potential QTL effectors
Author(s) -
Gopalakrishnan Kathirvel,
Thangavel Jayakumar,
Kumarasamy Sivarajan,
YergaWoolwine Shane,
Farms Phyllis,
Morgan Eric,
Kalinoski Andrea,
Liu Lijun,
Joe Bina
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.792.3
Subject(s) - congenic , biology , quantitative trait locus , spontaneously hypertensive rat , genetics , allele , gene , transcriptome , candidate gene , microbiology and biotechnology , gene expression , blood pressure , endocrinology
Individuals with normal blood pressure (BP) may possess susceptibility to the development of high BP, but the expression of these alleles is masked by the existence of other alleles conferring resistance to high BP. This phenomenon is exhibited in a congenic model of the hypertensive Dahl (S) rat with a <320.6Kb segment from the normotensive LEW rat. The BP of this congenic strain was higher than that of the S rat. In this report the genetic element causing this increase in BP was fine mapped to a region with a single gene Rffl with in 42.496 Kb. There were no coding sequence variants within Rffl , but significant cardiac differential expression was observed. Interestingly higher intrinsic cardiac hypertrophy was also evident in the congenic rats compared with S. Possibilities for the observed differential expression of Rffl were explored with a comprehensive genomic sequence miRNA analysis and transcriptome analysis of the critical region combined with functional analysis of Rffl . The data obtained through this study 1) identified a total of 171 variants within the critical region; 2) identified that 13 out of 110 predicted rat miRNAs within the critical region contained variants; 3) detected multiple gene networks perturbed between S and congenic rats; and 4) provided preliminary evidence for the functional significance of Rffl as a QTL effector.