RGD Reference Report - Multiple blood pressure loci with opposing blood pressure effects on rat chromosome 1 in a homologous region linked to hypertension on human chromosome 15. - Rat Genome Database

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Multiple blood pressure loci with opposing blood pressure effects on rat chromosome 1 in a homologous region linked to hypertension on human chromosome 15.

Authors: Mell, B  Abdul-Majeed, S  Kumarasamy, S  Waghulde, H  Pillai, R  Nie, Y  Joe, B 
Citation: Mell B, etal., Hypertens Res. 2015 Jan;38(1):61-7. doi: 10.1038/hr.2014.134. Epub 2014 Sep 18.
RGD ID: 9685377
Pubmed: PMID:25231251   (View Abstract at PubMed)
DOI: DOI:10.1038/hr.2014.134   (Journal Full-text)

Genetic dissection of blood pressure (BP) quantitative trait loci (QTLs) in rats has facilitated the fine-mapping of regions linked to the inheritance of hypertension. The goal of the current study was to further fine-map one such genomic region on rat chromosome 1 (BPQTL1b1), the homologous region of which on human chromosome 15 harbors BP QTLs, as reported by four independent studies. Of the six substrains constructed and studied, the systolic BP of two of the congenic strains were significantly lower by 36 and 27 mm Hg than that of the salt-sensitive (S) rat (P<0.0001, P=0.0003, respectively). The congenic segments of these two strains overlapped between 135.12 and 138.78 Mb and contained eight genes and two predicted miRNAs. None of the annotations had variants within expressed sequences. These data taken together with the previous localization resolved QTL1b1 with a 70% improvement from the original 7.39 Mb to the current 2.247 Mb interval. Furthermore, the systolic BP of one of the congenic substrains was significantly higher by 20 mm Hg (P<0.0001) than the BP of the S rat. The limits of this newly identified QTL with a BP increasing effect (QTL1b1a) were between 134.12 and 135.76 Mb, spanning 1.64 Mb, containing two protein-coding genes, Mctp2 and Rgma, and a predicted miRNA. There were four synonymous variants within Mctp2. These data provide evidence for two independent BP QTLs with opposing BP effects within the previously identified BP QTL1b1 region. Additionally, these findings illustrate the complexity underlying the genetic mechanisms of BP regulation, wherein inherited elements beyond protein-coding sequences or known regulatory regions could be operational.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  IDA 9685377as compared to parental SSRGD 
hypertension inducedIAGPcontrolled sodium content diet9685377compared to SS/JrRGD 
Hypotension  IDA 9685377as compared to parental SSRGD 

Phenotype Annotations    Click to see Annotation Detail View

Objects Annotated

QTLs
Bp375  (Blood pressure QTL 375)
Bp376  (Blood pressure QTL 376)

Objects referenced in this article
Marker D1Mco131 D1Mco131 Rattus norvegicus
Marker D1Mco132 D1Mco132 Rattus norvegicus
Marker D1Mco133 D1Mco133 Rattus norvegicus
Marker D1Mco134 D1Mco134 Rattus norvegicus
Marker D1Mco135 D1Mco135 Rattus norvegicus
Marker D1Mco136 D1Mco136 Rattus norvegicus
Marker D1Mco137 D1Mco137 Rattus norvegicus
QTL Bp313 Blood pressure QTL 313 Rattus norvegicus
QTL Bp344 Blood pressure QTL 344 Rattus norvegicus
QTL Bp93 Blood pressure QTL 93 Rattus norvegicus
Strain SS.LEW-(D1Mco36-D1Mco101)/Mco null Rattus norvegicus
Strain SS.LEW-(D1Mco36-D1Mco54)/Bj null Rattus norvegicus
Strain SS.LEW-(D1Mco36-D1Rat200)/Bj null Rattus norvegicus

Additional Information