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1 First Department of Internal Medicine, Shiga University of Medical Science, Otsu 520-2192; 2 Research Institute, National Cardiovascular Center, Suita 565-8565; and 3 Department of Clinical and Laboratory Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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High blood pressure is the leading cause of left ventricular hypertrophy (LVH); however, not all hypertensive patients develop LVH. Genetic factors are important in the development of LVH. With the use of F2 male rats from spontaneously hypertensive rats and Lewis rats, we performed a study to identify the quantitative trait loci (QTL) that influence left ventricular mass (LVM). Mean arterial pressure (MAP) was measured by the direct intra-arterial method in conscious animals, and LVM was determined at 24 wk of age. QTL analysis was done using 160 microsatellite markers for a genome-wide scan. Two loci that influenced body weight-adjusted LVM with logarithm of the odds scores >3.4 were found. One locus on chromosome 17 influenced LVM independently of MAP. Another locus on chromosome 7 influenced LVM and MAP. These findings indicate not only the existence of a gene on chromosome 7 that influences LVM in a manner dependent on blood pressure but also the existence of a gene on chromosome 17 that influences LVM independently of blood pressure.
blood pressure; spontaneously hypertensive rats; hypertension; linkage analysis
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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INCREASED LEFT VENTRICULAR (LV) mass is a strong independent predictor of cardiovascular morbidity and mortality (22). Although high blood pressure is the leading cause of LV hypertrophy (LVH) (9), not all hypertensive patients develop LVH (32). The correlation between the level of high blood pressure and LV mass is poor.
Factors other than blood pressure are recognized to be important in the development of LVH, including humoral factors such as catecholamine (7, 31) and ANG II (1, 27), the age at onset of high blood pressure (12), body size or obesity (21), insulin sensitivity (28), and genetic background (25, 34). Indeed, variations of the angiotensin-converting enzyme (14, 29) and aldosterone synthase (Cyp11b2) (18) gene have been suspected to influence LV mass.
With the use of crosses between hypertensive strains, between a hypertensive and a normotensive strain, and between normotensive strains, several linkage studies have indicated the existence of loci influencing LV mass independently of blood pressure (3, 8, 10, 11, 26, 30). Identification of genes contributing to LVH will help in evaluation of a patient's risk and provide clues to better therapeutic strategies.
In the present study, we used an animal model, spontaneously hypertensive rats (SHR/Izm), in an attempt to clarify the quantitative trait loci (QTL) influencing LV mass. With the recent development of rat and human genetic maps and comparative genetic maps (35), the present study may provide important clues to the identification of human genes contributing to LVH.
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METHODS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Experimental animals and genetic crosses. We studied 49 male F2 rats from an intercross of the SHR/Izm and normotensive Lewis rat (LEW/Crj) strains. These strains were chosen because of the relatively large phenotypic and genotypic differences between them; these provide the contrast required for informative linkage analysis. The SHR/Izm strain was obtained from Funabashi Farm (Funabashi, Japan). The LEW/Crj strain was obtained from Charles River (Atsugi, Japan).
Male SHR/Izm rats were mated with female LEW/Crj rats to produce F1 rats. Ten F1 male and ten F1 female rats were intercrossed to produce an F2 population consisting of 49 male rats. Only those litters with 11-15 pups were included in the present study. All animals were fed standard laboratory rat chow and had ad libitum access to drinking water. A 12:12-h light-dark regimen was maintained throughout the study. The study protocol was approved by the Ethical Committee of Shiga University of Medical Science.Determination of phenotypes. Arterial pressure was measured by the direct intra-arterial method in conscious animals at 24 wk of age. Body weight was measured, and the rats were anesthetized briefly with pentobarbital sodium (50 mg/kg ip) for insertion of polyethylene catheters (PE-50) into the right femoral artery. The catheters were passed under the skin and exposed in the interscapular region, and the rats were allowed to recover in individual cages with ad libitum access to food and water. Four days after the operation, mean arterial pressure (MAP) was recorded for 30 min with continuous sampling after stabilization of blood pressure. Blood pressure was measured between 2 and 5 P.M. Ventricular mass was determined by removing the whole heart, excising the atria, and dissecting the right ventricular wall from the LV and interventricular septum. Ventricles were blotted dry of blood before they were weighed.
Genotyping. DNA was isolated from the liver by use of standard procedures. PCR amplification was used to determine the genotype of the F2 animals at microsatellite loci that are polymorphic in the LEW/Crj × SHR/Izm cross. We used 160 microsatellite markers with an average intermarker distance of 12.5 centimorgans (cM) for a genome-wide scan. The rat genetic markers used in the present study were based on a previous report (15) and on information from Research Genetics (Huntsville, AL).
Linkage and statistical analysis. The linkage map was constructed using the Map Manager QT version 3.0b28 computer program (23, 24). After the map was constructed, we localized QTL relative to the position of the microsatellite markers as follows.
First, simple associations between the genotype at each locus and phenotypic variables were assessed by using ANOVA techniques. In addition, a linear regression analysis was performed using a dominant, recessive, or codominant genetic model [homozygous for LEW/Crj allele (LL) = 0, heterzygous (LS) + homozygous for SHR/Izm allele (SS) = 1 (dominant); LL + LS = 0, SS = 1 (recessive); LL = 0, LS = 1/2, SS = 1 (codominant)]. Marker loci that gave ANOVA or regression model F test P < 0.1 were considered significant. The second step of analysis involved a stepwise multiple regression analysis. Only loci that produced P < 0.1 in the first step were included in this second analysis. The third step involved estimation of the approximate position of individual QTL by use of composite interval mapping (17, 38) or multiple QTL model mapping (16) with the Map Manager QT computer program. These are based on the multiple QTL model. Like simple interval mapping, composite interval mapping evaluates the possibility of a target QTL at multiple analysis points across each intermarker interval. However, at each point it also includes the effect of one or more background markers. The inclusion of a background marker in the analysis helps in one of two ways, depending on whether the background marker and the target interval are linked. If they are not linked, inclusion of the background marker makes the analysis more sensitive to the presence of QTL in the target interval. If they are linked, inclusion of the background marker may help separate the target QTL from other linked QTLs on the distal side of the background marker (37, 38). Some other studies (5, 13, 33) that utilized multiple QTL model mapping have been reported. The results of the composite interval mapping were recorded as the likelihood ratio statistic. The likelihood ratio statistic can be converted to a conventional base-10 logarithm of odds (LOD) score by dividing it by 2ln 10 (24). The threshold values were taken from the guidelines of Lander and Kruglyak (20), in which the suggestive and significance thresholds of the dominant/recessive model are 2.0 and 3.4, respectively, and the suggestive and significance thresholds of the codominant model are 1.9 and 3.3, respectively.| |
RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Characterization of the phenotypes of the LEW/Crj, SHR/Izm, and F2
rats.
Table 1 shows the characterization of the
phenotypes of the LEW/Crj, SHR/Izm, and F2 male rats at 24 wk of age.
Significant differences were observed for MAP and LV mass between male
rats of the LEW/Crj and SHR/Izm strains. There were also differences in
body weight between the LEW/Crj and SHR/Izm strains.
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Coverage of the genetic linkage map.
Table 2 shows the genomic coverage of the
polymorphic markers. The selected genetic markers gave an average
genome marker distance of 12.5 cM.
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Composite interval mapping.
Tables 3 and
4 summarize the analysis of the
chromosomal mapping of QTL that influenced MAP and the LV mass index.
Multiple regression analyses revealed that a pair of loci [D7Mgh16
(codominant) and D2Rat15 (dominant)] had significant effects on MAP
(Table 3). The multiple regression analyses also revealed that two
pairs of loci [the pair D17Rat52 (dominant) and D1Rat84 (recessive) and the pair D7Rat112 (codominant) and D2Rat15 (dominant)] had significant effects on the LV mass index (Table 4).
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Loci linked to LV mass independent of MAP.
The locus on chromosome 17 was located around D17Rat52 (Fig.
1). The LOD score of the LV mass index at
D17Rat52 was 3.71, which was above the significance threshold of the
dominant model (3.4). The average value of the LV mass index for rats
homozygous for the SHR/Izm alleles at D17Rat52 was ~7% greater than
that for rats homozygous for the LEW/Crj alleles (Fig.
2). The LV mass index of heterozygous
rats was similar to that of rats homozygous for the SHR/Izm alleles,
suggesting a dominant mode of inheritance for the increased LV mass at
this locus. The LOD score of MAP at D17Rat52 was 0.41 (Fig. 1), which
was not above the significance threshold of the dominant model. There
were no significant differences in MAP among rats grouped according to
genotype at the D17Rat52 locus (Fig. 2). The LOD score of the LV mass
at D17Rat52 was 2.41 in the dominant model (data not shown), which was
above the suggestive threshold of the dominant model (2.0); however, it
was not above the significance threshold of the dominant model. The LOD
score of body weight at D17Rat52 was 0 in the dominant model (data not shown). The three groups defined by genotype at the D17Rat52 locus showed no differences in body weight (Fig. 2).
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Locus linked to LV mass and MAP.
We found another locus on chromosome 7 linked to the LV mass index and
MAP (Fig. 3). The locus for the LV mass
index was located at D7Rat112. The LOD score of the LV mass index at
the locus was 3.45, which was above the significance threshold of the
codominant model (3.3). Rats homozygous for the SHR/Izm alleles at the
D7Rat112 locus had an LV mass index ~11% greater than that of rats
homozygous for the LEW/Crj alleles (Fig.
4). The value of the LV mass index of
heterozygous rats at this locus was intermediate between the LV mass
indexes of the homozygous rats, suggesting that the mode of inheritance
is codominant. This locus was linked to MAP, with an LOD score of 3.95 (Fig. 3), which was higher than the significance threshold of the
codominant model (3.3). There were also significant differences in MAP
between rats homozygous for the SHR/Izm allele and those homozygous for
the LEW/Crj allele at the D7Rat112 locus, with higher values in those
homozygous for the SHR/Izm allele (Fig. 4). The LOD score of LV mass at
the locus between D7Rat112 and D7Rat20 was 3.39 in the codominant model
(data not show), which was above the significance threshold of the
codominant model. The LOD score of body weight was 0.85 in the
recessive model (data not shown), which was not above the significance
threshold of the recessive model (3.4).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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We found a locus that influenced the LV mass index independent of
MAP on rat chromosome 17. The locus was located around D17Rat52. D17Rat52 was near 17qter. Pravenec et al. (26) reported
that, in recombinant inbred strains derived from SHR and normotensive Brown-Norway rats, the marker of dopamine 1A receptor
(Drd1a) on chromosome 17 showed a strong correlation with LV
heart weight, but not with blood pressure. However, the marker for
Drd1a was located on 17p14, which is far from 17qter. The
gene for glutamic acid decarboxylase 2 (Gad2) is located
near D17Rat52 (35). Glutamic acid decarboxylase catalyzes
the synthesis of 
-aminobutyric acid from glutamic acid. The
relevance of this gene to the phenotypic variance in LV mass is not
clear. There is little information on genes near the locus around
D17Rat52. Yagil et al. (36) reported the existence of a
QTL for blood pressure at a locus around D17Mgh5 in their study that
used female F2 rats derived from salt-sensitive Sabra
hypertension-prone and salt-resistant Sabra hypertension-resistant rats. The QTL was also reported in the cross of the Dahl salt-sensitive and Lewis rats (4). However, we could not confirm this
locus in our study.
The locus that influenced MAP and the LV mass index on chromosome 7 was
near D7Rat112. The genes for lysozyme (Lyz), interferon- (Ifng), and hyaluronan synthase 2 (Has2) are
located near D7Rat112 (35). The relevance of these genes
to the phenotypic variance in LV mass and blood pressure is not clear.
Garrett et al. (6) reported a locus that influenced heart
weight and blood pressure around D7Mit5 in a cross of Dahl
salt-sensitive and Lewis strains. This locus is near those for steroid
11
-hydroxylase (Cyp11b1) and aldosterone synthase
(Cyp11b2). In their study, the Lewis allele was associated
with higher blood pressure and increased heart weight. On the other
hand, in the congenic and interval mapping studies with Dahl
salt-sensitive and Dahl salt-resistant strains, the Dahl salt-sensitive
rat Cyp11b allele was associated with higher blood pressure
and increased heart weight than was the Dahl salt-resistant rat
Cyp11b allele (2). Considering these
conflicting findings, we cannot conclude that Cyp11b1 or Cyp11b2 was the gene responsible for blood pressure and LV
mass QTL. However, the ratio of aldosterone to plasma renin activity of
the SHR/Izm strain was significantly higher than that of the LEW/Crj
strain in our study: 28.6 ± 4.4 versus 60.0 ± 12.2 pg · ml
1 · ng1 · ml1 · h1
(P < 0.05). Thus Cyp11b2 might be a
candidate gene for causing high blood pressure and LVH in the SHR/Izm model.
Although some other loci have been reported previously, they were not detected as QTL for blood pressure in the present study. For example, the renin locus was reported to be associated with blood pressure variation in an F2 population derived from SHR and Lewis rats (19). However, this locus was not identified as a QTL for blood pressure in the present study. This might be due to strain differences or the relatively small number of rats analyzed in the present study.
In conclusion, our findings indicate not only the existence of a gene on chromosome 7 that influences LV mass in a manner dependent on blood pressure but also the existence of a gene on chromosome 17 that influences LV mass independently of blood pressure.
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FOOTNOTES |
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Address for reprint requests and other correspondence: Y. Tsujita, First Dept. of Internal Medicine, Shiga University of Medical Science, Tsukinowa Seta, Otsu, Shiga 520-2192, Japan (E-mail: ytsujita{at}belle.shiga-med.ac.jp).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 19 November 1999; accepted in final form 18 May 2000.
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REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Baker, KM,
and
Aceto JF.
Angiotensin II stimulation of protein synthesis and cell growth in chick heart cells.
Am J Physiol Heart Circ Physiol
259:
H610-H618,
1990
2.
Cicila, GT,
Dukhanina OI,
Kurtz TW,
Walder R,
Garrett MR,
Dene H,
and
Rapp JP.
Blood pressure and survival of a chromosome 7 congenic strain bred from Dahl rats.
Mamm Genome
8:
896-902,
1997[ISI][Medline].
3.
Clark, JS,
Jeffs B,
Davidson AO,
Lee WK,
Anderson NH,
Bihoreau MT,
Brosnan MJ,
Devlin AM,
Kelman AW,
Lindpaintner K,
and
Dominiczak AF.
Quantitative trait loci in genetically hypertensive rats. Possible sex specificity.
Hypertension
28:
898-906,
1996
4.
Deng, AY,
Dene H,
Pravenec M,
and
Rapp JP.
Genetic mapping of two new blood pressure quantitative trait loci in the rat by genotyping endothelin system genes.
J Clin Invest
93:
2701-2709,
1994.
5.
Fijneman, RJ,
de Vries SS,
Jansen RC,
and
Demant P.
Complex interactions of new quantitative trait loci, Sluc1, Sluc2, Sluc3, and Sluc4, that influence the susceptibility to lung cancer in the mouse.
Nat Genet
14:
465-467,
1996[ISI][Medline].
6.
Garrett, MR,
Dene H,
Walder R,
Zhang QY,
Cicila GT,
Assadnia S,
Deng AY,
and
Rapp JP.
Genome scan and congenic strains for blood pressure QTL using Dahl salt-sensitive rats.
Genome Res
8:
711-723,
1998
7.
Gordon, AL,
Inchiosa MA, Jr,
and
Lehr D.
Isoproterenol-induced cardiomegaly: assessment of myocardial protein content, actomyosin ATPase and heart rate.
J Mol Cell Cardiol
4:
543-557,
1972[ISI][Medline].
8.
Hamet, P,
Kaiser MA,
Sun Y,
Page V,
Vincent M,
Kren V,
Pravenec M,
Kunes J,
Tremblay J,
and
Samani NJ.
HSP27 locus cosegregates with left ventricular mass independently of blood pressure.
Hypertension
28:
1112-1117,
1996.
9.
Harrap, SB,
Dominiczak AF,
Fraser R,
Lever AF,
Morton JJ,
Foy CJ,
and
Watt GC.
Plasma angiotensin II, predisposition to hypertension, and left ventricular size in healthy young adults.
Circulation
93:
1148-1154,
1996
10.
Harris, EL,
Phelan EL,
Thompson CM,
Millar JA,
and
Grigor MR.
Heart mass and blood pressure have separate genetic determinants in the New Zealand genetically hypertensive (GH) rat.
J Hypertens
13:
397-404,
1995[ISI][Medline].
11.
Innes, BA,
McLaughlin MG,
Kapuscinski MK,
Jacob HJ,
and
Harrap SB.
Independent genetic susceptibility to cardiac hypertrophy in inherited hypertension.
Hypertension
31:
741-746,
1998
12.
Isoyama, S,
Wei JY,
Izumo S,
Fort P,
Schoen FJ,
and
Grossman W.
Effect of age on the development of cardiac hypertrophy produced by aortic constriction in the rat.
Circ Res
61:
337-345,
1987
13.
Iwai, N,
Kinoshita M,
and
Shimoike H.
Chromosomal mapping of quantitative trait loci that influence renal hemodynamic functions.
Circulation
100:
1923-1929,
1999
14.
Iwai, N,
Ohmichi N,
Nakamura Y,
and
Kinoshita M.
DD genotype of the angiotensin-converting enzyme gene is a risk factor for left ventricular hypertrophy.
Circulation
90:
2622-2628,
1994
15.
Jacob, HJ,
Brown DM,
Bunker RK,
Daly MJ,
Dzau VJ,
Goodman A,
Koike G,
Kren V,
Kurtz T,
Lernmark A,
Levan G,
Mao Y,
Pettersson A,
Pravenec M,
Simon JS,
Szpirer C,
Szpirer J,
Trolliet MR,
Winer ES,
and
Lander ES.
A genetic linkage map of the laboratory rat, Rattus norvegicus.
Nat Genet
9:
63-69,
1995[ISI][Medline].
16.
Jansen, RC.
Interval mapping of multiple quantitative trait loci.
Genetics
135:
205-211,
1993[Abstract].
17.
Jiang, C,
and
Zeng ZB.
Multiple trait analysis of genetic mapping for quantitative trait loci.
Genetics
140:
1111-1127,
1995[Abstract].
18.
Kupari, M,
Hautanen A,
Lankinen L,
Koskinen P,
Virolainen J,
Nikkila H,
and
White PC.
Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function.
Circulation
97:
569-575,
1998
19.
Kurtz, TW,
Simonet L,
Kabra PM,
Wolfe S,
Chan L,
and
Hjelle BL.
Cosegregation of the renin allele of the spontaneously hypertensive rat with an increase in blood pressure.
J Clin Invest
85:
1328-1332,
1990.
20.
Lander, E,
and
Kruglyak L.
Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results.
Nat Genet
11:
241-247,
1995[ISI][Medline].
21.
Levy, D,
Anderson KM,
Savage DD,
Kannel WB,
Christiansen JC,
and
Castelli WP.
Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. The Framingham Heart Study.
Ann Intern Med
108:
7-13,
1988.
22.
Levy, D,
Garrison RJ,
Savage DD,
Kannel WB,
and
Castelli WP.
Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study.
N Engl J Med
322:
1561-1566,
1990[Abstract].
23.
Manly, KF.
A Macintosh program for storage and analysis of experimental genetic mapping data.
Mamm Genome
4:
303-313,
1993[ISI][Medline].
24.
Manly, KF,
and
Olson JM.
Overview of QTL mapping software and introduction to map manager QT.
Mamm Genome
10:
327-334,
1999[ISI][Medline].
25.
Post, WS,
Larson MG,
Myers RH,
Galderisi M,
and
Levy D.
Heritability of left ventricular mass: the Framingham Heart Study.
Hypertension
30:
1025-1028,
1997
26.
Pravenec, M,
Gauguier D,
Schott JJ,
Buard J,
Kren V,
Bila V,
Szpirer C,
Szpirer J,
Wang JM,
Huang H,
Lezin ES,
Spence MA,
Flodman P,
Printz M,
Lathrop GM,
Vergnaud G,
and
Kurtz TW.
Mapping of quantitative trait loci for blood pressure and cardiac mass in the rat by genome scanning of recombinant inbred strains.
J Clin Invest
96:
1973-1978,
1995.
27.
Sadoshima, J,
Xu Y,
Slayter HS,
and
Izumo S.
Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro.
Cell
75:
977-984,
1993[ISI][Medline].
28.
Sasson, Z,
Rasooly Y,
Bhesania T,
and
Rasooly I.
Insulin resistance is an important determinant of left ventricular mass in the obese.
Circulation
88:
1431-1436,
1993
29.
Schunkert, H,
Hense HW,
Holmer SR,
Stender M,
Perz S,
Keil U,
Lorell BH,
and
Riegger GA.
Association between a deletion polymorphism of the angiotensin-converting-enzyme gene and left ventricular hypertrophy.
N Engl J Med
330:
1634-1638,
1994
30.
Sebkhi, A,
Zhao L,
Lu L,
Haley CS,
Nunez DJ,
and
Wilkins MR.
Genetic determination of cardiac mass in normotensive rats: results from an F344×WKY cross.
Hypertension
33:
949-953,
1999
31.
Simpson, P.
Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha1-adrenergic response.
J Clin Invest
72:
732-738,
1983.
32.
Tingleff, J,
Munch M,
Jakobsen TJ,
Torp-Pedersen C,
Olsen ME,
Jensen KH,
Jorgensen T,
and
Kirchoff M.
Prevalence of left ventricular hypertrophy in a hypertensive population.
Eur Heart J
17:
143-149,
1996
33.
Van Der Schaar, W,
Alonso-Blanco C,
Leon-Kloosterziel KM,
Jansen RC,
van Ooijen JW,
and
Koornneef M.
QTL analysis of seed dormancy in Arabidopsis using recombinant inbred lines and MQM mapping.
Heredity
79:
190-200,
1997.
34.
Verhaaren, HA,
Schieken RM,
Mosteller M,
Hewitt JK,
Eaves LJ,
and
Nance WE.
Bivariate genetic analysis of left ventricular mass and weight in pubertal twins (the Medical College of Virginia twin study).
Am J Cardiol
68:
661-668,
1991[ISI][Medline].
35.
Watanabe, TK,
Bihoreau MT,
McCarthy LC,
Kiguwa SL,
Hishigaki H,
Tsuji A,
Browne J,
Yamasaki Y,
Mizoguchi-Miyakita A,
Oga K,
Ono T,
Okuno S,
Kanemoto N,
Takahashi E,
Tomita K,
Hayashi H,
Adachi M,
Webber C,
Davis M,
Kiel S,
Knights C,
Smith A,
Critcher R,
Miller J,
Thangarajah T,
Day PJR,
Hudson JR,
Irie Y,
Takagi T,
Nakamura Y,
Goodfellow PN,
Lathrop GM,
Tanigami A,
and
James MR.
A radiation hybrid map of the rat genome containing 5,255 markers.
Nat Genet
22:
27-36,
1999[ISI][Medline].
36.
Yagil, C,
Sapojnikov M,
Kreutz R,
Katni G,
Lindpaintner K,
Ganten D,
and
Yagil Y.
Salt susceptibility maps to chromosomes 1 and 17 with sex specificity in the Sabra rat model of hypertension.
Hypertension
31:
119-124,
1998
37.
Zeng, ZB.
Precision mapping of quantitative trait loci.
Genetics
136:
1457-1468,
1994[Abstract].
38.
Zeng, ZB.
Theoretical basis for separation of multiple linked gene effects in mapping quantitative trait loci.
Proc Natl Acad Sci USA
90:
10972-10976,
1993
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