Published online before print February 12, 2007, doi: 10.1161/01.HYP.0000259105.09235.56
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(Hypertension. 2007;49:740.)
© 2007 American Heart Association, Inc.
Brief Reviews |
Positional Cloning of Quantitative Trait Loci for Blood Pressure: How Close Are We?
A Critical Perspective
From the Research Centre, Centre Hospitalier de l’Université de Montréal, l’Université de Montréal Montréal, Québec, Canada.
Correspondence to Alan Y. Deng, Research Centre, Centre Hospitalier de l’Université de Montréal, Technopôle Angus, 2901 Rachel St East, Room 312, Montréal, Québec H1W 4A4, Canada. E-mail alan.deng@umontreal.ca
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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Introduction |
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Blood pressure (BP) in any human population exhibits as a continuous variable that fits a bell-shaped curve. Hypertensive individuals are those whose BP is maintained at one extreme of the curve and above a defined cutoff. Despite progress made in identifying the mechanisms underlying certain rare monogenic forms of hypertension,1,2 the etiology and pathogenesis of essential hypertension remain poorly understood.
Because existing human populations are genetically heterogeneous, and because environmental factors impacting on the pathogenesis of hypertension cannot be controlled in a given population, it is difficult to identify the molecular mechanisms that transduce the sequela of essential hypertension via direct human studies.3 To alleviate the drawbacks of human investigations, animal models, especially inbred rodents, have been developed and experimentally manipulated to identify quantitative trait loci (QTLs) for BP, because major confounding environmental factors, such as diet and genetic background, can be systematically controlled. Once identified in animal models, the molecular basis may be translated into physiological understandings of essential hypertension in humans.
It is with this expectation that efforts have been launched to identify the molecular basis of BP QTLs in animal models. Because the identification of individual QTLs is primarily based on their chromosome locations unbiased by, or unrestricted to, their physiological roles, positional cloning is believed to be the most efficient strategy.
Before we embark on discussions regarding QTL discovery, a definition is in order. Semantic arguments abound as to exactly what a QTL, that is, a locus,4 entails. Is it 1 gene or a collection of
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