Abstract We describe the in vivo phenotypes associated with three genomic intervals containing systemic lupus erythematosus (SLE)-susceptibility genes derived from SLE-prone NZM2410 strain on a C57BL/6 genome. These were identified previously via genome-wide analysis of SLE susceptibility (NZM2410 x C57BL/6)F1 backcross, and transferred independently background to produce congenic strains: B6.NZMc1 carrying Sle1, B6.NZMc4 Sle2, B6.NZMc7 Sle3. develops high titers IgG anti-nuclear...

An F 2 population ( n = 151) derived from Dahl salt-sensitive (S) and Lewis rats was raised on a 8% NaCl diet for 9 weeks analyzed blood pressure quantitative trait loci (QTL) by use of whole genome scan. Chromosomes 5 10 yielded lod scores linkage to that were significant; chromosomes 1, 2, 3, 8, 16, 17, 18 gave suggestive linkage. Chromosome 7 significant signal heart weight with lesser effect pressure. Congenic strains constructed introgressing low-blood-pressure QTL alleles 5, 10, 17...

Alleles of the inducible nitric oxide synthase locus (Nos2) cosegregated highly significantly (P < 0.0001) with blood pressure in an F2 population [F2(S x MNS), n = 171] derived from a cross inbred Dahl salt-sensitive (S) rats Milan normotensive (MNS). In contrast, alleles at constitutive brain (Nos1) did not cosegregate several populations. Nos2 was mapped on rat chromosome 10. Nine genetic markers, including angiotensin-converting enzyme (Ace) and loci spanning roughly 46 cM 10, all...

The endothelin system, consisting of a series potent vasoconstrictor peptides and their receptors, is potentially important in the control blood pressure. We found that gene coding for endothelin-2 (ET2), also known as vasoctive intestine peptide, cosegregated strongly with systolic pressure F2 population [F2(S x LEW)] derived from cross Dahl salt-sensitive (S) rat Lewis (LEW/NCrlBR) (LEW) rat. ET2 locus was assigned to chromosome 5. testis-specific histone (HITH) F2(S LEW) 17. Genetic maps...

Abstract Identification of the quantitative trait loci that influence blood pressure and cause genetic hypertension is a major challenge. Several genetically hypertensive rat strains exist can be used to locate by linkage analysis broad chromosomal regions containing loci. Such regions, then narrower subregions, moved among (ie, production congenic substrains) identify small However, ultimate positional cloning presents difficulty because variants involved are likely result in subtle changes...

Previously we presented suggestive evidence from an F2 segregating population for interaction on blood pressure (BP) between quantitative trait loci (QTL) rat chromosomes (Chr) 2 and 10. To prove the existence of such interaction, developed congenic strains Chr 10 by introgressing low BP QTL alleles into Dahl salt-sensitive (S) strain. A double strain was also constructed with both S background. The four (S, congenic, 2/10 congenic) were studied response to increased salt intake. An analysis...

A genetic map for rat chromosome 2 that includes five candidate genes blood pressure regulation was constructed in a region containing quantitative trait locus (QTL) pressure. Two F2 populations of male rats raised on high salt (8% NaCI) diet from weaning were studied: F2(WKY x S), derived cross Dahl salt-sensitive (S) and Wistar-Kyoto (WKY); F2(MNS S Milan normotensive strain (MNS). In both QTL localized between Na+,K(+)-ATPase alpha 1 isoform calmodulin-dependent protein kinase II-delta...

A genetic map for rat chromosome 1 was constructed using 66 microsatellite markers typed on either or both of two populations derived from inbred Dahl salt-sensitive (S) rats: F2(LEW x S) n = 151, and F2(WKY 159. These had been raised a high salt (8% NaCl) diet. Systolic blood pressure heart weight were found to be genetically linked separate regions in the population. One region centered around anonymous SA locus accounted 24 mmHg pressure. The other 55 cM cluster cytochromes P450 loci, 30...

Understanding the functional diversity of gut microbiome is essential for decoding its roles in health and disease. Using a deep-learning framework, we identified three archetypes defining healthy adult microbiomes, each characterized by specific metabolic potentials: sugar metabolism with branched-chain amino acid cell wall synthesis (Archetype 1), fatty TCA cycle 2), nitrogen 3). Archetype proximity linked to stability, 2 representing most resilient state, likely due flexibility....

Human epidemiological studies have statistically localized a multitude of quantitative trait loci (QTLs) for blood pressure (BP). However, their potential pathogenic mechanisms causing hypertension remain mysterious. To fill this void, we utilized congenic knock-in genetics to physiologically analyze the BP effects individual and combinational QTLs. The effect magnitude from single QTL in vivo ranged 33.8 59.8%. ‘Double’ multiple combinations QTLs exhibited same impact as alone....

Abstract Recent studies indicate that the production of 20-HETE by a P4504A2 enzyme in outer medulla kidney is reduced Dahl salt-sensitive (SS/Jr) rats, but contribution this abnormality to elevation loop Cl − transport and development hypertension model unknown. The present study found alleles at locus for gene cosegregate with blood pressure an F 2 population (n=151) derived from cross between SS/Jr Lewis rats ( P &lt;.0001). located region on rat chromosome 5 where quantitative trait was...

Abstract A quantitative trait locus (QTL) for blood pressure was previously detected by linkage analysis in a region of rat chromosome 2 using segregating populations derived from crosses the Dahl salt-sensitive (Dahl S) with rats Wistar-Kyoto (WKY) strain or Milan normotensive (MNS). Two congenic strains, S.WKY-D2N35/ Nep and S.MNS- Adh /D2Mit5, have been constructed replacing S homologous (ie, low QTL allele) either WKY MNS rat, respectively. Systolic pressures strains /D2Mit5 fed 2% NaCl...

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 animal models, but how they function together determining overall blood pressure (BP) physiological settings is unknown. Here, we systematically comprehensively performed pair-wise comparisons individual QTLs...

Objective To survey inbred rat strains for renin alleles and to test those effects on blood pressure Design Rat with different from the s allele carried by Dahl salt-sensitive (SS/Jr) rats were crossed SS/Jr subsequently intercrossed produce F2 populations. Thus, in each population segregation of a contrasting occurred. raised high-salt diet their pressures determined. The cosegregation was evaluated Methods Renin recognized variable number tandem repeats first intron gene Hind III site...

Our previous linkage studies indicated that there might be a blood pressure (BP) quantitative trait locus (QTL) on chromosome 3 (Chr 3) contrasting between the Dahl salt-sensitive (S) strain and Lewis (LEW) strain. To prove then to narrow down segment containing this QTL, five congenic strains have been generated by replacing various segments of S rats with homologous LEW rats. They are designated as S.L1, S.L2, S.L3, S.L4, S.L5, respectively. S.L5 substrains i.e., they contain substitutions...

Quantitative trait loci (QTLs) for blood pressure (BP) were found on chromosome 10 of Dahl salt-sensitive rats and are potentially important to human essential hypertension. But their identities how they influence BP together not known. Presently, we first fine mapped existing QTLs, C10QTL1, C10QTL2, C10QTL3, by constructing congenic strains. In the process, a new QTL, C10QTL4, was identified. Because intervals harboring C10QTL1 C10QTL4 contain maximum 16 possible genes, respectively,...

Total genome scan was carried out in 266 F 2 intercrosses from the Prague hypertriglyceridemic (HTG) rat that shares several clinical characteristics with human metabolic syndrome. Two loci for plasma triglycerides (TG) were localized on chromosome (Chr 2) (LOD 4.4, 3.2). The first locus overlapped syntenic region of syndrome and small, dense LDL, while second another LDL humans by comparative mapping approach. Loci TG Chr 13 3.3) 1 2.7) familial combined hyperlipidemia (FCHL) Finnish Dutch...

Objective To localize quantitative trait loci (QTL) in an animal model that is potentially relevant to human hypertension. Design and methods Four congenic strains have been constructed by replacing various segments of the Dahl salt-sensitive (S) rat those Lewis (LEW) rat. A marker-assisted approach was employed facilitate this process. When these were established, their blood pressures (BPs) measured telemetry compared with S Moreover, a search conducted find possible intermediate...