DESCRIPTION:

QTL Associated with Blood pressure. On Chromosome 17 with a LOD score= , p-value =0.001. From a(n) of

LABEL:

QTL-Bp369-Rat-Chr 17

SCORE TYPE:

Binary

DATE ADDED:

2015-06-10

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Chauvet C, Crespo K, Ménard A, Roy J, Deng AY

TITLE:

Modularization and epistatic hierarchy determine homeostatic actions of multiple blood pressure quantitative trait loci.

JOURNAL:

Human molecular genetics None None, Vol 22, pp. 4451-9

ABSTRACT:

1. Hum Mol Genet. 2013 Nov 15;22(22):4451-9. doi: 10.1093/hmg/ddt294. Epub 2013 Jun 28. Modularization and epistatic hierarchy determine homeostatic actions of multiple blood pressure quantitative trait loci. Chauvet C(1), Crespo K, Ménard A, Roy J, Deng AY. Author information: (1)Département de Medicine, Centre de Recherche, Centre Hospitalier de L'Université de Montréal (CRCHUM), Université de Montréal, Montréal, Québec, Canada. Comment in Physiol Genomics. 2013 Dec 15;45(24):1196-8. Physiol Genomics. 2013 Dec 15;45(24):1193-5. Hypertension, the most frequently diagnosed clinical condition world-wide, predisposes individuals to morbidity and mortality, yet its underlying pathological etiologies are poorly understood. So far, a large number of quantitative trait loci (QTLs) have been identified in both humans and animal models, but how they function together in determining overall blood pressure (BP) in physiological settings is unknown. Here, we systematically and comprehensively performed pair-wise comparisons of individual QTLs to create a global picture of their functionality in an inbred rat model. Rather than each of numerous QTLs contributing to infinitesimal BP increments, a modularized pattern arises: two epistatic 'blocks' constitute basic functional 'units' for nearly all QTLs, designated as epistatic module 1 (EM1) and EM2. This modularization dictates the magnitude and scope of BP effects. Any EM1 member can contribute to BP additively to that of EM2, but not to those of the same module. Members of each EM display epistatic hierarchy, which seems to reflect a related functional pathway. Rat homologues of 11 human BP QTLs belong to either EM1 or EM2. Unique insights emerge into the novel genetic mechanism and hierarchy determining BP in the Dahl salt-sensitive SS/Jr (DSS) rat model that implicate a portion of human QTLs. Elucidating the pathways underlying EM1 and EM2 may reveal the genetic regulation of BP. PMID: 23814039 [PubMed - indexed for MEDLINE] PUBMED: 23814039
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