Complete genome searches for quantitative trait loci controlling blood pressure and related traits in four segregating populations derived from Dahl hypertensive rats

Kato, Norihiro; Hyne, Gina; Mt, Bihoreau; Guyader, Dominique; Gm, Lathrop; Jp, Rapp

doi:10.1007/s003359900983

Cited by 55 publications

(35 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our objective for this study was to use substitution mapping to further delimit this RNO3 BP QTL-containing region, narrowing the interval used to identify candidate genes for future study. Another RNO3 q-terminal BP QTL was also identified using a salt-loaded F 2 (S 3 BN) population, although in contrast 1 with our results, overdominance was observed at this BP QTL (Kato et al 1999).…”

contrasting

confidence: 67%

Substitution Mapping in Dahl Rats Identifies Two Distinct Blood Pressure Quantitative Trait Loci Within 1.12- and 1.25-Mb Intervals on Chromosome 3

Lee

Westcott

et al. 2006

Genetics

View full text Add to dashboard Cite

Substitution mapping was used to refine the localization of blood pressure (BP) quantitative trait loci (QTL) within the congenic region of S.R-Edn3 rats located at the q terminus of rat chromosome 3 (RNO3). An F 2 (S 3 S.R-Edn3) population (n ¼ 173) was screened to identify rats having crossovers within the congenic region of RNO3 and six congenic substrains were developed that carry shorter segments of R-rat-derived RNO3. Five of the six congenic substrains had significantly lower BP compared to the parental S rat. The lack of BP lowering effect demonstrated by the S.R(ET3 3 5) substrain and the BP lowering effect retained by the S.R(ET3 3 2) substrain together define the RNO3 BP QTL-containing region as $4.64 Mb. Two nonoverlapping substrains, S.R(ET3 3 1) and S.R(ET3 3 6), had significantly lower BP compared to the S strain, indicating the presence of two distinct BP QTL in the RNO3 q terminus. The RNO3 q terminus was fine mapped with newly developed polymorphic markers to characterize the extent of the congenic regions. The two RNO3 BP QTL regions were thus defined as within intervals of 0.05-1.12 and 0.72-1.25 Mb, respectively. Also important was our difficulty in fine mapping and marker placement in this portion of the rat genome (and thus candidate gene identification) using the available genomic data, including the rat genome sequence.

show abstract

contrasting

confidence: 67%

Substitution Mapping in Dahl Rats Identifies Two Distinct Blood Pressure Quantitative Trait Loci Within 1.12- and 1.25-Mb Intervals on Chromosome 3

Lee

Westcott

et al. 2006

Genetics

View full text Add to dashboard Cite

show abstract

“…The QTL Bw2 colocalizes with a locus associated with body weight in a SS/jrxMNS cross. 22 The position of the locus Cmi1 coincides almost exactly with a QTL linked to aortic weight in a SS/jrxSHR cross 23 and a congenic interval associated with both blood pressure and heart weight in a SS/jrϫLew strain combination. 24 It is, however, nearly 100 cM distal to a QTL linked to cardiac mass in a SSϫSHR cross 25 Along the same line, previous studies have consistently shown the implication of QTL on chromosome 1 for the control of body weight, heart weight, and cardiac mass index in different rat crosses primarily designed to investigate the genetic control of complex disorders, including type 1 diabetes, type 2 diabetes, and hypertension.…”

Section: Discussionmentioning

confidence: 74%

Chromosomal Mapping of Quantitative Trait Loci Controlling Elastin Content in Rat Aorta

et al. 2005

Self Cite

View full text Add to dashboard Cite

Abstract-Extracellular matrix molecules such as elastin and collagens provide mechanical support to the vessel wall. In addition to its structural role, elastin is a regulator that maintains homeostasis through biologic signaling. Genetically determined minor modifications in elastin and collagen in the aorta could influence the onset and evolution of arterial pathology, such as hypertension and its complications. We previously demonstrated that the inbred Brown Norway (BN) rat shows an aortic elastin deficit in both abdominal and thoracic segments, partly because of a decrease in tropoelastin synthesis when compared with the LOU rat, that elastin gene polymorphisms in these strains do not significantly account for. After a genome-wide search for quantitative trait loci (QTL) influencing the aortic elastin, collagen, and cell protein contents in an F2 population derived from BN and LOU rats, we identified on chromosomes 2 and 14, 3 QTL specifically controlling elastin levels, and a further highly significant QTL on chromosome 17 linked to the level of cell proteins. We also mapped 3 highly significant QTL linked to body weight (on chromosomes 1 and 3) and heart weight (on chromosome 1) in the cross. This study demonstrates the polygenic control of the content of key components of the arterial wall. Such information represents a first step in understanding possible mechanisms involved in dysregulation of these parameters in arterial pathology. Key Words: aorta Ⅲ elastin Ⅲ genetics Ⅲ rats E lastin and collagens are the main extracellular matrix proteins of blood vessels. The functional properties of vessels, particularly of the major arteries and veins, are largely dependent on the absolute and relative quantities of these 2 constituents. 1 Elastic fibers composed of an elastin core surrounded by microfibrils are designed to maintain elastic function in tissues such as blood vessels, lungs, and skin. The biology of elastic fibers is complex because of their multiple components, tightly regulated developmental pattern of expression, multistep hierarchical assembly, unique elastomeric properties, and influence on cell phenotype.The elastin-null mice (ELN Ϫ/Ϫ ) die of obstructive arterial disease, 2 whereas the ELN ϩ/Ϫ mice have reduced absolute quantities of elastin and are hypertensive, phenotypes similar to those observed in patients with supravalvular aortic stenosis and Williams syndrome. In these patients, the elastin gene is mutated or deleted. 3,4 Investigating the genetic basis and pathophysiological consequences of the modulation of elastin levels, rather than the impact of absolute elastin deficit, is central to our understanding of mechanisms involved in arterial pathologies. The composition of the arterial extracellular matrix and the adaptative synthesis of elastin and collagen in hypertension may also influence the degree of reversibility of arterial remodeling in response to antihypertensive treatment and the development of hypertensive arteriopathy. Genetic studies of the aortic content of extracellu...

show abstract

“…No linkage of insulin, uric acid, FFA, or adiposity was reported for these two genomic regions; however, their importance is further supported by the overlapping findings of linkage of other metabolic syndrome-related traits. So, the region between D3Rat37 and D3Rat257 has been linked to glucose levels after pancreatectomy (30), body weight (14), cardiac mass (7,27), and heart rate (24), whereas loci within the more telomeric part of RNO3 were reported to influence variation of blood pressure, kidney mass (27), and urine albumin level (48). One of the possible candidate genes present in the region is a paired homeodomain transcription factor Pax6, a key regulator of pancreatic islet hormone gene transcription required for normal islet development (38).…”

Section: Genetic Architecture Of the Metabolic Syndromementioning

confidence: 99%

Dynamic genetic architecture of metabolic syndrome attributes in the rat

Šeda

Liška

Křenová

et al. 2005

Physiological Genomics

View full text Add to dashboard Cite

The polydactylous rat strain (PD/Cub) is a highly inbred (F Ͼ 90) genetic model of metabolic syndrome. The aim of this study was to analyze the genetic architecture of the metabolic derangements found in the PD/Cub strain and to assess its dynamics in time and in response to diet and medication. We derived a PD/Cub ϫ BN/Cub (Brown Norway) F2 intercross population of 149 male rats and performed metabolic profiling and genotyping and multiple levels of genetic linkage and statistical analyses at five different stages of ontogenesis and after high-sucrose diet feeding and dexamethasone administration challenges. The interval mapping analysis of 83 metabolic and morphometric traits revealed over 50 regions genomewide with significant or suggestive linkage to one or more of the traits in the segregating PD/Cub ϫ BN/Cub population. The multiple interval mapping showed that, in addition to "single" quantitative train loci, there are more than 30 pairs of loci across the whole genome significantly influencing the variation of particular traits in an epistatic fashion. This study represents the first whole genome analysis of metabolic syndrome in the PD/Cub model and reveals several new loci previously not connected to the genetics of insulin resistance and dyslipidemia. In addition, it attempts to present the concept of "dynamic genetic architecture" of metabolic syndrome attributes, evidenced by shifts in the genetic determination of syndrome features during ontogenesis and during adaptation to the dietary and pharmacological influences.quantitative trait loci; pharmacogenetics; nutrigenetics; triglyceride; insulin resistance; obesity METABOLIC SYNDROME is a complex condition arising from an intricate network of interacting genetic and environmental factors. The dynamics of the increase in its worldwide prevalence qualify the syndrome as a major healthcare issue for years to come. The syndrome comprises several clinical features, each representing a complex trait of its kind, i.e., hypertriglyceridemia, hyperinsulinemia, insulin resistance, obesity, and hypertension (11,36). It is therefore self evident that detailed analysis of the genetic determinants underlying such metabolic clustering is rather complicated in the general human population and only somewhat more feasible in particular circumstances, e.g., in population isolates (32). Although some progress has been made and several studies succeeded in identification of genes potentially involved in the pathogenesis of metabolic syndrome (13,17,35,51), its genetic determination is far from being fully understood.As in other complex diseases, defined animal models of metabolic syndrome are proving to be important tools for deciphering the causative genes and gene-gene and geneenvironment interactions (8). There are numerous rodent strains expressing all or a subset of metabolic syndrome attributes found in humans [e.g., Otsuka Long-Evans Tokushima Fatty rat (16), Goto-Kakizaki rat (10), hereditary hypertriglyceridemic rat (53, 54), and spontaneously hypertensive rat ...

show abstract

Complete genome searches for quantitative trait loci controlling blood pressure and related traits in four segregating populations derived from Dahl hypertensive rats

Cited by 55 publications

References 41 publications

Substitution Mapping in Dahl Rats Identifies Two Distinct Blood Pressure Quantitative Trait Loci Within 1.12- and 1.25-Mb Intervals on Chromosome 3

Substitution Mapping in Dahl Rats Identifies Two Distinct Blood Pressure Quantitative Trait Loci Within 1.12- and 1.25-Mb Intervals on Chromosome 3

Chromosomal Mapping of Quantitative Trait Loci Controlling Elastin Content in Rat Aorta

Dynamic genetic architecture of metabolic syndrome attributes in the rat

Contact Info

Product

Resources

About