期刊
HYPERTENSION RESEARCH
卷 38, 期 1, 页码 61-67出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/hr.2014.134
关键词
BP QTL; Dahl S rat; HSA15; RNO1
资金
- National Heart Lung and Blood Institute of the National Institutes of Health [HL020176, HL112641]
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 27mmHg 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 138.78Mb 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 7.39Mb to the current 2.247Mb interval. Furthermore, the systolic BP of one of the congenic substrains was significantly higher by 20mmHg (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.
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