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John P. Rapp - One of the best experts on this subject based on the ideXlab platform.

  • substitution mapping of a blood pressure quantitative trait locus to a 2 73 mb region on rat chromosome 1
    Journal of Hypertension, 2003
    Co-Authors: Bina Joe, Michael R Garrett, Howard Dene, John P. Rapp
    Abstract:

    OBJECTIVE To improve the localization of a blood pressure quantitative trait locus (BP QTL) on rat chromosome (RNO) 1. METHODS Congenic substrains were derived from the progenitor Congenic strains S.LEW(D1Mco4X1) and S.LEW(D1Mco4X5) which previously localized a BP QTL (region 2) to a 17cM interval on RNO1. The newly developed Congenic substrains, along with control Dahl salt-sensitive (S) rats were fed a 2% NaCl diet for 24 days before their BP was compared by both tail-cuff and radiotelemetry methods. RESULTS By comparing BP of these Congenic substrains to that of S rats, we have refined the location of the BP QTL2 region to a 2.73 Mb genomic interval that contains 19 annotated genes in the latest rat genome assembly (version 2.1). Slc9a3, the gene encoding the Na(+)/H(+) exchanger 3, originally a candidate gene in the BP QTL2 region, is excluded based on its map location. CONCLUSION Substitution mapping was used to reduce a BP QTL on RNO1 from 17 centimorgans (cM) to approximately 1.4 cM (= 2.73 Mb). This region now contains 19 annotated rat candidate genes.

  • two closely linked interactive blood pressure qtl on rat chromosome 5 defined using Congenic dahl rats
    Physiological Genomics, 2002
    Co-Authors: Michael R Garrett, John P. Rapp
    Abstract:

    Previously we reported the construction of a Congenic strain, S.LEW(5), spanning a large region of rat chromosome 5. The Lewis (LEW) strain was the donor, and the Dahl salt-sensitive (S) strain was the recipient. The Congenic strain included a blood pressure quantitative trait locus (QTL). In the present work, a series of nine Congenic substrains were constructed from S.LEW(5) which defined two closely linked blood pressure QTL in the region previously thought to contain only one. LEW low-blood-pressure alleles at both QTL were required for a major effect on blood pressure. Neither LEW allele alone had a significant effect on blood pressure. The two QTL were localized to regions 6.3 and 4.6 cM, and these were 1.0 cM apart.

  • two linked blood pressure quantitative trait loci on chromosome 10 defined by dahl rat Congenic strains
    Hypertension, 2001
    Co-Authors: Michael R Garrett, Alan Y. Deng, Oksana I Dukhanina, Xiaotong Zhang, John P. Rapp
    Abstract:

    A quantitative trait locus (QTL) for blood pressure was previously detected on rat chromosome 10 (RNO10) by linkage analysis and confirmed by the construction of Congenic strains that encompass large regions of RNO10. In the present study, the rat RNO10 blood pressure QTL was dissected by the further construction of Congenic substrains. The original Congenic region was shown to contain 2 blood pressure QTLs (QTL 1 and QTL 2) ≈24 cM apart. These were localized to a <2.6-cM region between markers D10Rat27 and D10Rat24 for QTL 1 and to a <3.2-cM region between D10Rat12 and D10Mco70 for QTL 2. Comparative mapping suggests that the rat RNO10 QTL 2 could be localized very close to a blood pressure QTL described by sib-pair analysis on human chromosome 17, but this is not definitively established because of multiple and complex chromosomal rearrangements between rodents and humans.

  • linkage analysis and construction of a Congenic strain for a blood pressure qtl on rat chromosome 9
    Genomics, 1998
    Co-Authors: John P. Rapp, Michael R Garrett, Howard Dene, Haijin Meng, Barbara Hoebee, Mark G Lathrop
    Abstract:

    Abstract A blood pressure quantitative trait locus was found (LOD = 5.0) on rat chromosome 9 using a large F 2 population ( N = 233) derived from Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats. The F 2 rats were fed 8% NaCl diet for 8 weeks. A Congenic strain introgressing the R low-blood-pressure QTL allele on chromosome 9 into the S strain was constructed. The Congenic strain, designated S.R(chr 9), had a lower blood pressure (19 mm Hg, P P

  • construction of a double Congenic strain to prove an epistatic interaction on blood pressure between rat chromosomes 2 and 10
    Journal of Clinical Investigation, 1998
    Co-Authors: John P. Rapp, Michael R Garrett, Alan Y. Deng
    Abstract:

    Previously we presented suggestive evidence from an F2 segregating population for an interaction on blood pressure (BP) between quantitative trait loci (QTL) on rat chromosomes (Chr) 2 and 10. To prove the existence of such an interaction, we developed Congenic strains for Chr 2 and 10 by introgressing the low BP QTL alleles into the Dahl salt-sensitive (S) strain. A double Congenic strain was also constructed with both the Chr 2 and 10 low BP QTL alleles on the S background. The four strains (S, Chr 2 Congenic, Chr 10 Congenic, and Chr 2/10 double Congenic) were studied for BP response to increased salt intake. An analysis of variance showed significant main effects of Chr 2, Chr 10, and a significant interaction between Chr 2 and 10 on BP and heart weight (all P < 0.0001). The interaction accounted for 24 mmHg of BP and 79 mg of heart weight. Thus, the discovery and proof of epistatic interactions are clearly critical to understanding the genetics of blood pressure.

Alan Y. Deng - One of the best experts on this subject based on the ideXlab platform.

  • multiple quantitative trait loci for blood pressure interacting epistatically and additively on dahl rat chromosome 2
    Hypertension, 2005
    Co-Authors: Julie Dutil, Vasiliki Eliopoulos, Sophie Charron, Johanne Tremblay, Pavel Hamet, Alan Y. Deng
    Abstract:

    Our previous work demonstrated 2 quantitative trait loci (QTLs), C2QTL1 and C2QTL2, for blood pressure (BP) located on chromosome (Chr) 2 of Dahl salt-sensitive (DSS) rats. However, for a lack of markers, the 2 Congenic strains delineating C2QTL1 and C2QTL2 could not be separated. The position of the C2QTL1 was only inferred by comparing 2 Congenic strains, one having and another lacking a BP effect. Furthermore, it was not known how adjacent QTLs would interact with one another on Chr 2. In the current investigation, first, a critical chromosome marker was developed to separate 2 C2QTLs. Second, a Congenic substrain was created to cover a chromosome fragment thought to harbor C2QTL1. Finally, a series of Congenic strains was produced to systematically and comprehensively cover the entire Chr 2 segment containing C2QTL2 and other regions previously untested. Consequently, a total of 3 QTLs were discovered, with C2QTL3 located between C2QTL1 and C2QTL2. C2QTL1, C2QTL2, and C2QTL3 reside in chromosome segments of 5.7 centiMorgan (cM), 3.5 cM, and 1.5 cM, respectively. C2QTL1 interacted epistatically with either C2QTL2 or C2QTL3, whereas C2QTL2 and C2QTL3 showed additive effects to each other. These results suggest that BP QTLs closely linked in a segment interact epistatically and additively to one another on Chr 2.

  • complete and overlapping Congenics proving the existence of a quantitative trait locus for blood pressure on dahl rat chromosome 17
    Physiological Genomics, 2005
    Co-Authors: Myrian Grondin, Julie Dutil, Raphaelle Lambert, Vasiliki Eliopoulos, Sophie Charron, Anita Ariyarajah, Yishu Deng, Myriam Moujahidine, Alan Y. Deng
    Abstract:

    Linkage studies suggested that a quantitative trait locus (QTL) for blood pressure (BP) was present in a region on chromosome 17 (Chr 17) of Dahl salt-sensitive (DSS) rats. A subsequent Congenic strain targeting this QTL, however, could not confirm it. These conflicting results called into question the validity of localization of a QTL by linkage followed by the use of a Congenic strain made with an incomplete chromosome coverage. To resolve this issue, we constructed five new Congenic strains, designated C17S.L1 to C17S.L5, that completely spanned the ±2 LOD confidence interval supposedly containing the QTL. Each Congenic strain was made by replacing a segment of the DSS rat by that of the normotensive Lewis (LEW) rat. The only section to be LL homozygous is the region on Chr 17 specified in a Congenic strain, as evidenced by a total genome scan. The results showed that BPs of C17S.L1 and C17S.L2 were lower ( P 0.6) from that of DSS rats. Consequently, a BP QTL must be located in an interval of ∼15 cM shared between C17S.L1 and C17S.L2 and unique to them both, as opposed to C17S.L3, C17S.L4, and C17S.L5. The present study illustrates the importance of thorough chromosome coverage, the necessity for a genome-wide screening, and the use of “negative” controls in physically mapping a QTL by Congenic strains.

  • dissecting quantitative trait loci into opposite blood pressure effects on dahl rat chromosome 8 by Congenic strains
    Journal of Hypertension, 2004
    Co-Authors: Anita Ariyarajah, Ana Palijan, Julie Dutil, Yishu Deng, Kalyani Prithiviraj, Alan Y. Deng
    Abstract:

    Objective Our previous linkage analyses showed that there was likely a quantitative trait locus (QTL) for blood pressure (BP) on chromosome 8 (Chr 8) in the strain comparison between the Dahl salt-sensitive (S) and the Lewis (LEW) rats. The current work is to delineate the chromosome interval harboring this QTL by using Congenic strains with different chromosome substitutions. Methods Two Congenic strains were produced by replacing different segments of the S rats with the homologous segments of the LEW rats. A genome-wide marker screening was utilized to accelerate this process. The two strains generated are designated as C8S.L1 and C8S.L2, respectively. BPs of the rats were measured by telemetry. Results C8S.L1 showed a BP lower than that of S rats. In contrast, C8S.L2 did not have chromosome overlaps with C8S.L1, but unexpectedly, exhibited a BP-raising effect, higher than that of S rats. Conclusion There are at least two QTLs present in a section of Chr 8 that possess opposite BP effects. The current Congenic work reveals not only the presence of QTLs, but the complexity of QTLs on BP. The novel Congenic strain with hypertension more severe than S provides a new model for studies in elucidating physiological mechanisms controlling BP.

  • two linked blood pressure quantitative trait loci on chromosome 10 defined by dahl rat Congenic strains
    Hypertension, 2001
    Co-Authors: Michael R Garrett, Alan Y. Deng, Oksana I Dukhanina, Xiaotong Zhang, John P. Rapp
    Abstract:

    A quantitative trait locus (QTL) for blood pressure was previously detected on rat chromosome 10 (RNO10) by linkage analysis and confirmed by the construction of Congenic strains that encompass large regions of RNO10. In the present study, the rat RNO10 blood pressure QTL was dissected by the further construction of Congenic substrains. The original Congenic region was shown to contain 2 blood pressure QTLs (QTL 1 and QTL 2) ≈24 cM apart. These were localized to a <2.6-cM region between markers D10Rat27 and D10Rat24 for QTL 1 and to a <3.2-cM region between D10Rat12 and D10Mco70 for QTL 2. Comparative mapping suggests that the rat RNO10 QTL 2 could be localized very close to a blood pressure QTL described by sib-pair analysis on human chromosome 17, but this is not definitively established because of multiple and complex chromosomal rearrangements between rodents and humans.

  • construction of a double Congenic strain to prove an epistatic interaction on blood pressure between rat chromosomes 2 and 10
    Journal of Clinical Investigation, 1998
    Co-Authors: John P. Rapp, Michael R Garrett, Alan Y. Deng
    Abstract:

    Previously we presented suggestive evidence from an F2 segregating population for an interaction on blood pressure (BP) between quantitative trait loci (QTL) on rat chromosomes (Chr) 2 and 10. To prove the existence of such an interaction, we developed Congenic strains for Chr 2 and 10 by introgressing the low BP QTL alleles into the Dahl salt-sensitive (S) strain. A double Congenic strain was also constructed with both the Chr 2 and 10 low BP QTL alleles on the S background. The four strains (S, Chr 2 Congenic, Chr 10 Congenic, and Chr 2/10 double Congenic) were studied for BP response to increased salt intake. An analysis of variance showed significant main effects of Chr 2, Chr 10, and a significant interaction between Chr 2 and 10 on BP and heart weight (all P < 0.0001). The interaction accounted for 24 mmHg of BP and 79 mg of heart weight. Thus, the discovery and proof of epistatic interactions are clearly critical to understanding the genetics of blood pressure.

Michael R Garrett - One of the best experts on this subject based on the ideXlab platform.

  • substitution mapping of a blood pressure quantitative trait locus to a 2 73 mb region on rat chromosome 1
    Journal of Hypertension, 2003
    Co-Authors: Bina Joe, Michael R Garrett, Howard Dene, John P. Rapp
    Abstract:

    OBJECTIVE To improve the localization of a blood pressure quantitative trait locus (BP QTL) on rat chromosome (RNO) 1. METHODS Congenic substrains were derived from the progenitor Congenic strains S.LEW(D1Mco4X1) and S.LEW(D1Mco4X5) which previously localized a BP QTL (region 2) to a 17cM interval on RNO1. The newly developed Congenic substrains, along with control Dahl salt-sensitive (S) rats were fed a 2% NaCl diet for 24 days before their BP was compared by both tail-cuff and radiotelemetry methods. RESULTS By comparing BP of these Congenic substrains to that of S rats, we have refined the location of the BP QTL2 region to a 2.73 Mb genomic interval that contains 19 annotated genes in the latest rat genome assembly (version 2.1). Slc9a3, the gene encoding the Na(+)/H(+) exchanger 3, originally a candidate gene in the BP QTL2 region, is excluded based on its map location. CONCLUSION Substitution mapping was used to reduce a BP QTL on RNO1 from 17 centimorgans (cM) to approximately 1.4 cM (= 2.73 Mb). This region now contains 19 annotated rat candidate genes.

  • two closely linked interactive blood pressure qtl on rat chromosome 5 defined using Congenic dahl rats
    Physiological Genomics, 2002
    Co-Authors: Michael R Garrett, John P. Rapp
    Abstract:

    Previously we reported the construction of a Congenic strain, S.LEW(5), spanning a large region of rat chromosome 5. The Lewis (LEW) strain was the donor, and the Dahl salt-sensitive (S) strain was the recipient. The Congenic strain included a blood pressure quantitative trait locus (QTL). In the present work, a series of nine Congenic substrains were constructed from S.LEW(5) which defined two closely linked blood pressure QTL in the region previously thought to contain only one. LEW low-blood-pressure alleles at both QTL were required for a major effect on blood pressure. Neither LEW allele alone had a significant effect on blood pressure. The two QTL were localized to regions 6.3 and 4.6 cM, and these were 1.0 cM apart.

  • two linked blood pressure quantitative trait loci on chromosome 10 defined by dahl rat Congenic strains
    Hypertension, 2001
    Co-Authors: Michael R Garrett, Alan Y. Deng, Oksana I Dukhanina, Xiaotong Zhang, John P. Rapp
    Abstract:

    A quantitative trait locus (QTL) for blood pressure was previously detected on rat chromosome 10 (RNO10) by linkage analysis and confirmed by the construction of Congenic strains that encompass large regions of RNO10. In the present study, the rat RNO10 blood pressure QTL was dissected by the further construction of Congenic substrains. The original Congenic region was shown to contain 2 blood pressure QTLs (QTL 1 and QTL 2) ≈24 cM apart. These were localized to a <2.6-cM region between markers D10Rat27 and D10Rat24 for QTL 1 and to a <3.2-cM region between D10Rat12 and D10Mco70 for QTL 2. Comparative mapping suggests that the rat RNO10 QTL 2 could be localized very close to a blood pressure QTL described by sib-pair analysis on human chromosome 17, but this is not definitively established because of multiple and complex chromosomal rearrangements between rodents and humans.

  • linkage analysis and construction of a Congenic strain for a blood pressure qtl on rat chromosome 9
    Genomics, 1998
    Co-Authors: John P. Rapp, Michael R Garrett, Howard Dene, Haijin Meng, Barbara Hoebee, Mark G Lathrop
    Abstract:

    Abstract A blood pressure quantitative trait locus was found (LOD = 5.0) on rat chromosome 9 using a large F 2 population ( N = 233) derived from Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats. The F 2 rats were fed 8% NaCl diet for 8 weeks. A Congenic strain introgressing the R low-blood-pressure QTL allele on chromosome 9 into the S strain was constructed. The Congenic strain, designated S.R(chr 9), had a lower blood pressure (19 mm Hg, P P

  • construction of a double Congenic strain to prove an epistatic interaction on blood pressure between rat chromosomes 2 and 10
    Journal of Clinical Investigation, 1998
    Co-Authors: John P. Rapp, Michael R Garrett, Alan Y. Deng
    Abstract:

    Previously we presented suggestive evidence from an F2 segregating population for an interaction on blood pressure (BP) between quantitative trait loci (QTL) on rat chromosomes (Chr) 2 and 10. To prove the existence of such an interaction, we developed Congenic strains for Chr 2 and 10 by introgressing the low BP QTL alleles into the Dahl salt-sensitive (S) strain. A double Congenic strain was also constructed with both the Chr 2 and 10 low BP QTL alleles on the S background. The four strains (S, Chr 2 Congenic, Chr 10 Congenic, and Chr 2/10 double Congenic) were studied for BP response to increased salt intake. An analysis of variance showed significant main effects of Chr 2, Chr 10, and a significant interaction between Chr 2 and 10 on BP and heart weight (all P < 0.0001). The interaction accounted for 24 mmHg of BP and 79 mg of heart weight. Thus, the discovery and proof of epistatic interactions are clearly critical to understanding the genetics of blood pressure.

Bina Joe - One of the best experts on this subject based on the ideXlab platform.

  • refined mapping of blood pressure quantitative trait loci using Congenic strains developed from two genetically hypertensive rat models
    Hypertension Research, 2011
    Co-Authors: Sivarajan Kumarasamy, Phyllis Farms, Kathirvel Gopalakrishnan, Edward J Toland, Shane Yergawoolwine, Eric E Morgan, Bina Joe
    Abstract:

    Previously linkage and substitution mapping were conducted between the Dahl Salt-sensitive (S) rat and the Spontaneously Hypertensive Rat (SHR) to address the hypothesis that genetic contributions to blood pressure (BP) in two genetically hypertensive rat strains are different. Among the BP quantitative trait loci (QTLs) detected, two are located on chromosome 9 within large genomic segments. The goal of the current study was to develop new iterations of Congenic substrains, to further resolve both of these BP QTLs on chromosome 9 as independent Congenic segments. A total of 10 new Congenic substrains were developed and characterized. The newly developed Congenic substrains S.SHR(9)x8Ax11A and S.SHR(9)x10Ax1, with introgressed segments of 2.05 and 6.14 Mb, represented the shortest genomic segments. Both of these Congenic substrains, S.SHR(9)x8Ax11A and S.SHR(9)x10Ax1 lowered BP of the S rat by 56 mm Hg (P<0.001) and 15 mm Hg (P<0.039), respectively. The BP measurements were corroborated by radiotelemetry. Urinary protein excretion was significantly lowered by SHR alleles within S.SHR(9)x10Ax1 but not by S.SHR(9)x8Ax11A. The shorter of the two Congenic segments, 2.05 Mb was further characterized and found to contain a single differentially expressed protein-coding gene, Tomoregulin-2 (Tmeff2). The protein expression of Tmeff2 was higher in the S rat compared with S.SHR(9)x8Ax11A, which also had lower cardiac hypertrophy as measured by echocardiography. Tmeff2 is known to be upregulated in patients from multiple cohorts with cardiac hypertrophy. Taken together, Tmeff2 can be prioritized as a candidate gene for hypertension and associated cardiac hypertrophy in both rats and in humans.

  • augmented rififylin is a risk factor linked to aberrant cardiomyocyte function short qt interval and hypertension
    Hypertension, 2011
    Co-Authors: Kathirvel Gopalakrishnan, Sivarajan Kumarasamy, Andrea Kalinoski, Phyllis Farms, Shane Yergawoolwine, Eric E Morgan, Xiaochen Liu, Lijun Liu, Bina Joe
    Abstract:

    Using Congenic strains of the Dahl salt-sensitive (S) rat introgressed with genomic segments from the normotensive Lewis rat, a blood pressure quantitative trait locus was previously mapped within 104 kb on chromosome 10. The goal of the current study was to conduct extensive phenotypic studies and to further fine-map this locus. At 14 weeks of age, the blood pressure of the Congenic rats fed a low-salt diet was significantly higher by 47 mm Hg (P<0.001) compared with that of the S rat. A time-course study showed that the blood pressure effect was significant from very young ages of 50 to 52 days (13 mm Hg; P<0.01). The Congenic strain implanted with electrocardiography transmitters demonstrated shorter-QT intervals and increased heart rate compared with S rats (P<0.01). The average survival of the Congenic strain was shorter (134 days) compared with the S rat (175 days; P<0.0007). The critical region was narrowed to <42.5 kb containing 171 variants and a single gene, rififylin. Both the mRNA and protein levels of rififylin were significantly higher in the hearts of the Congenic strain. Overexpression of rififylin is known to delay endocytic recycling. Endocytic recycling of fluorescently labeled holotransferrin from cardiomyocytes of the Congenic strain was slower than that of S rats (P<0.01). Frequency of cardiomyocyte beats in the Congenic strain (62±9 bpm) was significantly higher than that of the S rat (24±6 bpm; P<0.001). Taken together, our study provides evidence to suggest that early perturbations in endocytic recycling caused by the overexpression of Rffl is a novel physiological mechanism potentially underlying the development of hypertension.

  • substitution mapping of a blood pressure quantitative trait locus to a 2 73 mb region on rat chromosome 1
    Journal of Hypertension, 2003
    Co-Authors: Bina Joe, Michael R Garrett, Howard Dene, John P. Rapp
    Abstract:

    OBJECTIVE To improve the localization of a blood pressure quantitative trait locus (BP QTL) on rat chromosome (RNO) 1. METHODS Congenic substrains were derived from the progenitor Congenic strains S.LEW(D1Mco4X1) and S.LEW(D1Mco4X5) which previously localized a BP QTL (region 2) to a 17cM interval on RNO1. The newly developed Congenic substrains, along with control Dahl salt-sensitive (S) rats were fed a 2% NaCl diet for 24 days before their BP was compared by both tail-cuff and radiotelemetry methods. RESULTS By comparing BP of these Congenic substrains to that of S rats, we have refined the location of the BP QTL2 region to a 2.73 Mb genomic interval that contains 19 annotated genes in the latest rat genome assembly (version 2.1). Slc9a3, the gene encoding the Na(+)/H(+) exchanger 3, originally a candidate gene in the BP QTL2 region, is excluded based on its map location. CONCLUSION Substitution mapping was used to reduce a BP QTL on RNO1 from 17 centimorgans (cM) to approximately 1.4 cM (= 2.73 Mb). This region now contains 19 annotated rat candidate genes.

Nelson Ruizopazo - One of the best experts on this subject based on the ideXlab platform.

  • sex specific effects on spatial learning and memory and sex independent effects on blood pressure of a 3 3 mbp rat chromosome 2 qtl region in dahl salt sensitive rats
    PLOS ONE, 2013
    Co-Authors: Victoria L M Herrera, Khristine A Pasion, Ann Marie Moran, Nelson Ruizopazo
    Abstract:

    Epidemiological studies have consistently found that hypertension is associated with poor cognitive performance. We hypothesize that a putative causal mechanism underlying this association is due to genetic loci affecting both blood pressure and cognition. Consistent with this notion, we reported several blood pressure (BP) quantitative trait loci (QTLs) that co-localized with navigational performance (Nav)-QTLs influencing spatial learning and memory in Dahl rats. The present study investigates a chromosome 2 region harboring BP-f4 and Nav-8 QTLs. We developed two Congenic strains, S.R2A and S.R2B introgressing Dahl R-chromosome 2 segments into Dahl S chromosome 2 region spanning BP-f4 and Nav-8 QTLs. Radiotelemetric blood pressure analysis identified only S.R2A Congenic rats with lower systolic blood pressure (females: −26.0 mmHg, P = 0.003; males: −30.9 mmHg, P<1×10−5), diastolic blood pressure (females: −21.2 mmHg, P = 0.01; males: −25.7 mmHg, P<1×10−5), and mean arterial pressure (females: −23.9 mmHg, P = 0.004; males: −28.0 mmHg, P<1×10−5) compared with corresponding Dahl S controls, confirming the presence of BP-f4 QTL on rat chromosome 2. The S.R2B Congenic segment did not affect blood pressure. Testing of S.R2A, S.R2B, and Dahl S male rats in the Morris water maze (MWM) task revealed significantly decreased spatial navigation performance in S.R2A male Congenic rats when compared with Dahl S male controls (P<0.05). The S.R2B Congenic segment did not affect performance of the MWM task in males. The S.R2A female rats did not differ in spatial navigation when compared with Dahl S female controls, indicating that the Nav-8 effect on spatial navigation is male-specific. Our results suggest the existence of a single QTL on chromosome 2 176.6–179.9 Mbp region which affects blood pressure in both males and females and cognition solely in males.

  • dahl s r rat Congenic strain analysis confirms and defines a chromosome 17 spatial navigation quantitative trait locus to 10 mbp
    PLOS ONE, 2013
    Co-Authors: Victoria L M Herrera, Khristine A Pasion, Nelson Ruizopazo
    Abstract:

    A quantitative trait locus (QTL) linked with ability to find a platform in the Morris Water Maze (MWM) was located on chromosome 17 (Nav-5 QTL) using intercross between Dahl S and Dahl R rats. We developed two Congenic strains, S.R17A and S.R17B introgressing Dahl R-chromosome 17 segments into Dahl S chromosome 17 region spanning putative Nav-5 QTL. Performance analysis of S.R17A, S.R17B and Dahl S rats in the Morris water maze (MWM) task showed a significantly decreased spatial navigation performance in S.R17B Congenic rats when compared with Dahl S controls (P = 0.02). The S.R17A Congenic segment did not affect MWM performance delimiting Nav-5 to the chromosome 17 65.02–74.66 Mbp region. Additional fine mapping is necessary to identify the specific gene variant accounting for Nav-5 effect on spatial learning and memory in Dahl rats.

  • dahl s x r Congenic strain analysis confirms and defines a chromosome 5 female specific blood pressure quantitative trait locus to 7 mbp
    PLOS ONE, 2012
    Co-Authors: Victoria L M Herrera, Khristine A Pasion, Ann Marie Moran, Nelson Ruizopazo
    Abstract:

    : The detection of multiple sex-specific blood pressure (BP) quantitative trait loci (QTLs) in independent total genome analyses of F2 (Dahl S x R)-intercross male and female rat cohorts confirms clinical observations of sex-specific disease cause and response to treatment among hypertensive patients, and mandate the identification of sex-specific hypertension genes/mechanisms. We developed and studied two Congenic strains, S.R5A and S.R5B introgressing Dahl R-chromosome 5 segments into Dahl S chromosome 5 region spanning putative BP-f1 and BP-f2 QTLs. Radiotelemetric non-stressed 24-hour BP analysis at four weeks post-high salt diet (8% NaCl) challenge, identified only S.R5B Congenic rats with lower SBP (-26.5 mmHg, P = 0.002), DBP (-23.7 mmHg, P = 0.004) and MAP (-25.1 mmHg, P = 0.002) compared with Dahl S female controls at four months of age confirming BP-f1 but not BP-f2 QTL on rat chromosome 5. The S.R5B Congenic segment did not affect pulse pressure and relative heart weight indicating that the gene underlying BP-f1 does not influence arterial stiffness and cardiac hypertrophy. The results of our Congenic analysis narrowed BP-f1 to chromosome 5 coordinates 134.9-141.5 Mbp setting up the basis for further fine mapping of BP-f1 and eventual identification of the specific gene variant accounting for BP-f1 effect on blood pressure.