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At least 685 records · Page 38Linked to original sources
PubMed2003

High resolution mapping of an arthritis susceptibility locus on rat chromosome 4, and characterization of regulated phenotypes.

The rat Natural Killer cell gene Complex (NKC) encodes molecules that can regulate immunity. It is located within an interval on DA rat chromosome 4 (RNO4) that is linked to immune-mediated inflammatory joint diseases, including oil-induced arthritis (OIA). We aimed to test the hypothesis that NKC regulates arthritis, by performing advanced mapping of arthritis and additional phenotypes induced by an intradermal injection of incomplete Freund's adjuvant-oil. Reciprocal transfer of RNO4 intervals established that alleles from DA confer arthritis susceptibility to inbred LEW.1AV1 and PVG.1AV1 rats, whereas LEW.1AV1 and PVG.1AV1 alleles confer resistance to inbred DA. Subcongenic strains with PVG.1AV1 alleles introduced on DA allowed mapping of disease predisposition to 0.8 cM on the cytogenetic band 4q42, within the quantitative trait locus oil-induced arthritis-2 (Oia2), but outside the NKC. Alleles in Oia2 regulated arthritis in an additive fashion, and determined arthritis incidence, severity and day of onset, in both males and females. Besides macroscopic joint-inflammation, Oia2 also regulated other oil-induced phenotypes, including lymphoplasia and plasma levels of the inflammation marker alpha1-acid glycoprotein. The high-impact Oia2 region harbors gene sequences similar to human C3AR1, Ribosomal protein L7, DNAJA2, C-type lectins, C1s and CD163. These candidate disease genes may be of general interest, given that rat 4q42, and the syntenic mouse 6F2 and human 12p13 regions are linked to several inflammatory diseases, including rheumatoid arthritis.

Animals↗
PubMed2005

Quantitative genome scan and Ordered-Subsets Analysis of autism endophenotypes support language QTLs.

Autism is a neurodevelopmental syndrome with early childhood onset and deficits in three behavioral and cognitive dimensions: language, social skills and repetitive or restrictive behaviors. We hypothesized that using these endophenotypes would provide more power to detect linkage than the diagnosis of autism. Previously, we reported results for a nonparametric quantitative trait locus (QTL) genome scan in 152 families with autism, which revealed a linkage peak related to spoken language on 7q35. Here, we present the results of a nonparametric QTL scan of autism endophenotypes in 291 multiplex families, including the original 152. The strongest evidence for an 'age at first word' QTL was on chromosomes 3q at 147 cM (Z=3.10, P<0.001), and 17q at 93 cM (Z=2.84, P=0.002), both represent novel susceptibility loci for autism endophenotypes. There was also support for a previously identified autism peak on chromosome 17 at 43 cM (Z=2.22, P=0.013) with 'age at first phrase'. The 7q35 language peak was attenuated (Z=2.05, P=0.02) compared with the original finding. To explore the possibility of increased heterogeneity resulting from the addition of 135 families to the sample, we conducted an Ordered-Subsets Analysis on chromosome 7; these results suggest that the 132 autism families with the earliest average age at first word are responsible for the QTL on 7q35. This locus on 7q35 may harbor a gene contributing variability in spoken language that is not uniquely related to language delay in autism.

Autistic Disorder↗
PubMed2003

Identification of quantitative trait loci that modify the severity of hereditary spherocytosis in wan, a new mouse model of band-3 deficiency.

Defects in red blood cell (RBC) membrane skeleton components cause hereditary spherocytosis (HS). Clinically, HS varies significantly even among individuals with identical gene defects, illustrating the profound effects of genetic background on disease severity. We exploited a new spontaneous mouse model, wan, which arose on the inbred C3H/HeJ strain, to identify quantitative trait loci (QTL) that modify the HS phenotype. Homozygous wan mice have severe HS due to a complete deficiency of erythroid band 3. A QTL analysis of RBC count, hemoglobin, hematocrit, mean corpuscular volume (MCV), and mean corpuscular hemoglobin content (MCHC) was performed in wan/wan mice from an F2 intercross between C3H/HeJ(+/wan) and CAST/Ei(+/+) F1 hybrids. Hematologic and survival data from C3H, CAST/Ei F2 wan homozygotes support the hypothesis that genetic modifiers significantly influence the band-3 null HS phenotype. Significant QTL were identified for the MCV trait only, suggesting that RBC membrane characteristics are a target for modifier gene action. The most significant quantitative trait locus, Hsm1 (hereditary spherocytosis modifier 1), localizes to mouse Chromosome 12 and is dominant. The peak LOD score was obtained with a marker for Spnb1 encoding erythroid beta-spectrin, an obvious candidate gene.

Animals↗
PubMed2004

Further evidence for a QTL influencing body mass index on chromosome 7p from a genome-wide scan in Dutch families.

Obesity is a rapidly growing threat to public health, driven by the increased occurrence of high caloric diets and sedentary lifestyles. Within this environment, genetic influences may largely determine inter-individual differences in obesity-related traits. To map genes involved in weight regulation, we performed a genome-wide linkage scan for body mass index (BMI), a reliable measure of total body fat, in 192 Dutch families including 315 twins and 210 siblings with data on BMI. Using variance components linkage analysis, regions with LOD-scores greater than 2 were observed on 6p25.1 (LOD-score, 2.13) and 7p21.1 (LOD-score, 2.40). LOD-scores higher than 1 were found on chromosomes 3, 13, 15 and 21. Of note, evidence for the putative quantitative trait locus for BMI on 7p was obtained previously from such diverse populations as Mexican-Americans, Asians and Nigerians, suggesting that the underlying genes may effect weight regulation in diverse environments. An obvious positional candidate in the 7p linkage region is the gene encoding neuropeptide Y (NPY) that controls satiety and food intake.

Adolescent↗
PubMed2001

Improving the comparative map of SSC2p-q13 by sample sequencing of BAC clones.

To improve the comparative map for pig chromosome 2 and increase the gene density on this chromosome, a porcine bacterial artificial chromosome (BAC) library was screened with 17 microsatellite markers and 18 genes previously assigned to pig chromosome 2. Fifty-one BAC clones located in the region of a maternally imprinted quantitative trait locus for backfat thickness (BFT) were identified. From these BACs 372 kb were sample sequenced. The average read length of a subclone was 442 basepair (bp). Contig assembly analysis showed that every bp was sequenced 1.28 times. Subsequently, sequences were compared with sequences in the nucleotide databases to identify homology with other mammalian sequences. Sequence identity was observed with sequences derived from 35 BACs. The average percentage identity with human sequences was 87.6%, with an average length of 143 bp. In total, sample sequencing of all BACs resulted in sequence identity with 29 human genes, 13 human expressed sequence tags (ESTs), 17 human genomic clones, one rat gene, one porcine gene and nine porcine ESTs. Eighteen genes located on human chromosome 11 and 19, and seven genes from other human locations, one rat gene and one porcine gene were assigned to pig chromosome 2 for the first time. The new genes were added to the radiation hybrid map at the same position as the locus from which the BAC that was sequenced was derived. In total 57 genes were placed on the radiation hybrid map of SSC2p-q13.

Animals↗
PubMed1999

Quantitative trait loci affecting risk for pentobarbital withdrawal map near alcohol withdrawal loci on mouse chromosomes 1, 4, and 11.

Barbiturate dependence is associated with the development of physiological dependence (withdrawal), tolerance, or a maladaptive pattern of drug use. Analysis of strain and individual differences with animal models for physiological dependence liability are useful means to identify potential genetic determinants of liability in humans. Behavioral and quantitative trait locus (QTL) mapping analyses were conducted with mice that are resistant versus sensitive to pentobarbital withdrawal. With a multistage genetic mapping strategy, a pentobarbital withdrawal QTL (Pbw1) was mapped to the distal region of mouse Chromosome (Chr) 1 and may be identical to an alcohol withdrawal QTL mapped to this chromosomal region. Two suggestive QTLs for pentobarbital withdrawal, both in proximity to QTLs definitely mapped for alcohol withdrawal, were also tentatively identified. These were on Chr 11 in proximity to a gene cluster including several members of the GABAA receptor gene family, and on Chr 4 near a locus associated with beta-carboline-induced seizure severity. These data represent the first detection and mapping of loci influencing risk for physiological dependence on barbiturates, and suggest the involvement of common genes in physiological dependence on pentobarbital and alcohol.

Animals↗
PubMed2003

Genetic loci for diet-induced atherosclerotic lesions and plasma lipids in mice.

Genetic factors independent of those affecting plasma lipid levels are a major contributor to risk for atherosclerosis in humans, yet the basis for these is poorly understood. This study examined plasma lipids and diet-induced atherosclerosis in 16-month-old female mice of strains C56BL/6J and DBA/2J. Mice of the parental strains, from recombinant inbred strains derived from these (BXD RI), and F(2) progeny were fed an atherogenic diet for 16 weeks, beginning at 1 year of age. This induced atherosclerotic lesion formation in both parental strains, accompanied by increased plasma LDL levels. However, individual BXD RI strains and the BXD F(2) mice demonstrated a range of atherosclerotic lesion formation that was not or at best weakly correlated with plasma lipid levels. Quantitative trait locus (QTL) analysis of the BXD F(2) mice identified a locus with significant linkage (lod 4.5) for aortic lesion size on Chromosome (Chr) 10 that was independent of plasma lipids. Other loci with suggestive or significant linkage for various plasma lipid measures were identified on Chr 2, 3, 4, 5, 6, 7, 11, and 17. In this intercross, the genes primarily influencing atherosclerosis are distinct from those controlling plasma lipid levels.

Animals↗
PubMed1998

Dopamine beta-hydroxylase: two polymorphisms in linkage disequilibrium at the structural gene DBH associate with biochemical phenotypic variation.

Levels of the enzyme dopamine beta-hydroxylase (DbetaH) in the plasma and cerebrospinal fluid (CSF) are closely related biochemical phenotypes. Both are under strong genetic control. Linkage and association studies suggest the structural gene encoding DbetaH (locus name, DBH) is a major locus influencing plasma activity of DbetaH. This study examined relationships of DBH genotype determined at two polymorphic sites (a previously described GT repeat, referred to as the DBH STR and a single-base substitution at the 3' end of DBH exon 2, named DBH*444 g/a), to CSF levels of DbetaH protein in European-American schizophrenic patients, and to plasma DbetaH activity in European-American patients with mood or anxiety disorders. We also investigated linkage disequilibrium (LD) between the polymorphisms in the pooled samples from those European-American subjects (n=104). Alleles of DBH*444 g/a were associated with differences in mean values of CSF DbetaH levels. Alleles at both polymorphisms were associated with plasma DbetaH activity. Significant LD was observed between respective alleles with similar apparent influence on biochemical phenotype. Thus, allele A3 of the DBH STR was in positive LD with DBH*444a, and both alleles were associated with lower plasma DbetaH activity. DBH STR allele A4 was in positive LD with DBH*444 g, and both alleles were associated with higher plasma DbetaH activity. The results confirm that DBH is a major quantitative trait locus for plasma DbetaH activity, and provide the first direct evidence that DBH also influences CSF DbetaH levels. Both polymorphisms examined in this study appear to be in LD with one or more functional polymorphisms that mediate the influence of allelic variation at DBH on DbetaH biochemical phenotypic variation

Anxiety Disorders↗
PubMed2006

Genome-wide linkage of plasma adiponectin reveals a major locus on chromosome 3q distinct from the adiponectin structural gene: the IRAS family study.

Adiponectin (APM1) is an adipocyte-derived peptide that contributes to glucose, lipid, and energy homeostasis. We assessed the genetic basis of plasma adiponectin in Hispanic-American and African-American families enrolled through the Insulin Resistance Atherosclerosis Study Family Study. A 10-cM genome scan was performed in two batches: an original set (set 1) consisting of 66 families (45 Hispanic American and 21 African American) and a replication set (set 2) consisting of 66 families (45 Hispanic American and 21 African American). Adiponectin levels were measured by radioimmunoassay in 1,727 individuals from 131 of 132 families. Linkage analysis was carried out in Hispanic Americans and African Americans separately in set 1, set 2, and the pooled set (set 1 plus set 2), with and without diabetic subjects. A major gene was mapped to 3q27 with a logarithm of odds (LOD) score of 8.21 in the Hispanic-American sample. Ninety-six unrelated individuals were screened for polymorphisms in the APM1 gene, and 18 single nucleotide polymorphisms (SNPs) were genotyped in the Hispanic-American sample. Plasma adiponectin level was modestly associated with two SNPs and their accompaning haplotypes. Incorporating each or both SNPs in the linkage analysis, however, did not significantly reduce the LOD score. Therefore, a quantitative trait locus at 3q27, likely distinct from the APM1 gene, contributes to the variation of plasma adiponectin levels in the Hispanic-American population.

Adiponectin↗
PubMed2005

Genomewide linkage analysis of soluble transferrin receptor plasma levels.

Genetic control of soluble transferrin receptor (sTfR) levels was demonstrated using family-based studies (GAIT, Genetic Analysis of Idiopathic Thrombophilia project); moreover, a genetic relationship was observed between sTfR and the risk for thrombosis, suggesting that these phenotypes shared genetic determinants. We studied the regions that control sTfR. To assess such regions, a full genome scan was carried out using 604 highly polymorphic deoxyribonucleic acid markers (resolution 7.3 cM) in 21 extended pedigrees (358 individuals). Then, a quantitative trait linkage analysis was performed using variance components methods. The genomewide scan linkage analysis showed two regions (quantitative trait locus or QTL) with significant limit of detection (LOD) scores (2q23.14, LOD score = 2.64, nominal p = 0.00024; 3q21.2, LOD score = 1.94, nominal p = 0.0014). There were no obvious candidate genes in these regions. In conclusion, this linkage analysis suggested the existence of a QTL in 2q23.14 that probably harbored a gene (or genes) controlling sTfR levels. Moreover, a second linkage signal was observed in 3q21.2; albeit the evidence for this second locus was lower. The next step will be to identify the gene(s) and its possible involvement in thrombosis and iron homeostasis.

Chromosome Mapping↗
PubMed2001

Linkage of high-density lipoprotein-cholesterol concentrations to a locus on chromosome 9p in Mexican Americans.

High-density lipoproteins (HDLs) are anti-atherogenic lipoproteins that have a major role in transporting cholesterol from peripheral tissues to the liver, where it is removed. Epidemiologic studies have shown that low levels of high-density lipoprotein-cholesterol (HDL-C) are associated with an increased incidence of coronary heart disease and an increased mortality rate, indicating a protective role of high concentrations of HDL-C against atherogenesis and the development of coronary heart disease. HDL-C level is influenced by several genetic and nongenetic factors. Nongenetic factors include smoking, which has been shown to decrease the HDL-C level. Exercise and alcohol have been shown to increase HDL-C levels. Decreased HDL-C is often associated with other coronary heart disease risk factors such as obesity, hyperinsulinemia and insulin resistance, hypertriglyceridemia and hypertension. Although several genes have been identified for rare forms of dyslipidemia, the genes accounting for major variation in HDL-C levels have yet to be identified. Using a multipoint variance components linkage approach, we found strong evidence of linkage (lod score=3.4; P=0.00004) of a quantitative trait locus (QTL) for HDL-C level to a genetic location between markers D9S925 and D9S741 on chromosome 9p in Mexican Americans. A replication study in an independent set of Mexican American families confirmed the existence of a QTL on chromosome 9p.

Adult↗
PubMed1997

Location of the first genetic locus, PKDr1, controlling autosomal dominant polycystic kidney disease in Han:SPRD cy/+ rat.

The Han:SPRD cy/+ strain develops a form of slowly progressive disease that appears similar in many respects to that seen in the autosomal dominant polycystic kidney disease (ADPKD) in humans. We have performed a total genome scan in an experimental backcross population derived from affected Han:SPRD cy/+ rat (PKD) and non-affected Wistar Ottawa Karlsburg rat (WOK) using 117 microsatellite markers. The genetic dissection of PKD allowed us to map on rat chromosome 5, a quantitative trait locus (QTL) controlling PKD, kidney mass and plasma urea concentration. The homology region is likely to reside on human chromosome 8. The gene responsible for PKD in Han:SPRD cy/+ rat is neither PKD1, localised on human chromosome 16, nor PKD2, localised on human chromosome 4. Therefore, we propose that this new locus be denoted PKDr1. The detection of the PKDr1 locus and associated QTL should accelerate research into the genetic causes of ADPKD.

Animals↗
PubMed2002

Two closely linked interactive blood pressure QTL on rat chromosome 5 defined using congenic Dahl rats.

Previously we reported the construction of a congenic strain, S.LEW, 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 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.

Alleles↗
PubMed2003

Identification of QTLs influencing combustion quality in Miscanthus sinensis Anderss. II. Chlorine and potassium content.

Chlorine and potassium content are important traits related to combustion quality of Miscanthus species. These traits were analysed in a cross between F(1.1) and F(1.7) entries of Miscanthus sinensis Anderss, both lines offspring of the cross between MS-90-2 and MS-88-110. Quantitative trait locus (QTL) analyses were performed on a previous linkage map constructed with the offspring cross mapping strategy. The mapqtl 4.0 package was used to perform QTL analyses. Six potential QTLs were detected with data collected over a 2-year period. Of these, four were associated with chlorine and two with potassium. These results could be used as an initial step to develop a marker-aided selection programme for biomass with low mineral content.

Chlorine↗
PubMed2004

Quantitative genetic analysis of glucose transporter 4 mRNA levels in baboon adipose.

OBJECTIVE: Glucose transporter 4 (GLUT4) is an insulin-responsive glucose transporter expressed in adipose tissue. A decrease of the mRNA abundance of GLUT4 in adipose tissue has been observed in conditions of insulin resistance. The objective was to conduct quantitative genetic analyses using GLUT4 mRNA levels in omental adipose tissue of baboons as a novel phenotype. RESEARCH METHODS AND PROCEDURES: A blood sample and a biopsy of omental adipose tissue were collected from 418 adult, pedigreed baboons. Total RNA was isolated from adipose tissue biopsies, and GLUT4 mRNA abundance was assayed by quantitative, real-time reverse transcription-polymerase chain reaction. Insulin and glucose were determined in fasting plasma by standard methods. Quantitative genetic analyses were conducted using GLUT4 mRNA, insulin, and glucose as quantitative traits. RESULTS: GLUT4 mRNA expression in omental adipose tissue was heritable (h(2) = 0.23, p = 0.001). Bivariate genetic analyses revealed a significant genetic correlation (rho(G)) between GLUT4 mRNA abundance and both body weight (rho(G) = 0.63, p = 0.007), BMI (rho(G) = 0.59, p = 0.02) and insulin (rho(G) = 0.72, p = 0.04). A genome scan was conducted, and a quantitative trait locus was detected on chromosome 10p12 with a logarithm of the odds ratio score of 1.1. DISCUSSION: GLUT4 mRNA abundance in omental adipose tissue has a significant genetic component. These findings suggest that expression of GLUT4 mRNA, plasma insulin levels, and body weight may be regulated by common genes.

Adipose Tissue↗
PubMed2003

Sex effect on clinical and immunologic quantitative trait loci in a murine model of rheumatoid arthritis.

OBJECTIVE: To explore the effect of sex on clinical and immunologic traits in major histocompatibility complex-matched (H-2d) F(2) hybrid mice with proteoglycan (PG)-induced arthritis and to identify how the quantitative trait locus (QTL) on the X chromosome influences the onset QTL of another chromosome. METHODS: (BALB/c x DBA/2)F(2) hybrid mice were immunized with cartilage PG, and a genome-wide linkage analysis was performed using >200 simple sequence-length polymorphic markers. The major clinical traits (susceptibility, onset, and severity) were assessed, and PG-specific T and B cell responses, and the production of proinflammatory and antiinflammatory cytokines (tumor necrosis factor alpha, interleukin-1 [IL-1], IL-6, interferon-gamma, IL-4, IL-10, and IL-12) were measured in 133 arthritic and 426 nonarthritic female and male F(2) hybrid mice. The major clinical and immunologic traits were linked to genetic loci, and potential linkages among these QTLs and the effect of sex were analyzed. RESULTS: Thirteen QTLs reported in previous studies were confirmed. Binary traits (susceptibility to arthritis) and disease onset were female specific and were identified on chromosomes 3, 7, 10, 11, 13, and X. QTLs for disease severity were mostly male specific and were located on chromosomes 1, 4, 5, 8, 14, 15, and 19. In addition, we identified 4 new QTLs for the onset of arthritis on chromosomes 3, 4, and 11, and 1 new QTL for severity on chromosome 14; all showed a strong gender association. A locus on the X chromosome interacted with a QTL on chromosome 10, and these 2 loci together seemed to control disease incidence and onset. Most of the clinical traits (QTLs) shared common regions with the immunologic traits and frequently showed a locus-locus interaction. CONCLUSION: Numerous immunologic QTLs overlap with clinical QTLs, thus providing information about possible mechanisms underlying QTL function. Disease susceptibility and onset showed predominant linkage with the female sex, under the control of a QTL on the X chromosome, while the severity QTLs were more strongly linked to the male sex.

Animals↗
PubMed2006

Causal inference of regulator-target pairs by gene mapping of expression phenotypes.

BACKGROUND: Correlations between polymorphic markers and observed phenotypes provide the basis for mapping traits in quantitative genetics. When the phenotype is gene expression, then loci involved in regulatory control can theoretically be implicated. Recent efforts to construct gene regulatory networks from genotype and gene expression data have shown that biologically relevant networks can be achieved from an integrative approach. In this paper, we consider the problem of identifying individual pairs of genes in a direct or indirect, causal, trans-acting relationship. RESULTS: Inspired by epistatic models of multi-locus quantitative trait (QTL) mapping, we propose a unified model of expression and genotype to identify quantitative trait genes (QTG) by extending the conventional linear model to include both genotype and expression of regulator genes and their interactions. The model provides mapping of specific genes in contrast to standard linkage approaches that implicate large QTL intervals typically containing tens of genes. In simulations, we found that the method can often detect weak trans-acting regulators amid the background noise of thousands of traits and is robust to transcription models containing multiple regulator genes. We reanalyze several pleiotropic loci derived from a large set of yeast matings and identify a likely alternative regulator not previously published. However, we also found that many regulators can not be so easily mapped due to the presence of cis-acting QTLs on the regulators, which induce close linkage among small neighborhoods of genes. QTG mapped regulator-target pairs linked to ARN1 were combined to form a regulatory module, which we observed to be highly enriched in iron homeostasis related genes and contained several causally directed links that had not been identified in other automatic reconstructions of that regulatory module. Finally, we also confirm the surprising, previously published results that regulators controlling gene expression are not enriched for transcription factors, but we do show that our more precise mapping model reveals functional enrichment for several other biological processes related to the regulation of the cell. CONCLUSION: By incorporating interacting expression and genotype, our QTG mapping method can identify specific regulator genes in contrast to standard QTL interval mapping. We have shown that the method can recover biologically significant regulator-target pairs and the approach leads to a general framework for inducing a regulatory module network topology of directed and undirected edges that can be used to identify leads in pathway analysis.

Algorithms↗
PubMed2006

Development of overt proteinuria in the Munich Wistar Frömter rat is suppressed by replacement of chromosome 6 in a consomic rat strain.

In a cross between the Munich Wistar Frömter (MWF) rat and spontaneously hypertensive rats (SHR), a major quantitative trait locus (QTL) was identified on rat chromosome 6 (RNO6) that demonstrated the strongest linkage to albuminuria among several QTL identified. The QTL represented the only locus that is linked to both early-onset albuminuria and increased renal interstitial fibrosis in adult animals. A consomic MWF-6(SHR) strain in which chromosome 6 from SHR was introgressed into the MWF background therefore was generated to test the relevance of this QTL. Phenotype analysis at 8 wk of age revealed that early onset of albuminuria in MWF with a 55-fold elevation of urinary albumin excretion compared with SHR (P < 0.0001) was completely abolished in MWF-6(SHR). Time-course analysis until week 24 demonstrated only a moderate increase of urinary albumin excretion in MWF-6(SHR), whereas MWF reached levels in the nephrotic range (16.6 +/- 3.5 versus 162.6 +/- 16.0 mg/24 h; P < 0.0001). At this age, analysis of glomerulosclerosis, tubulointerstitial damage, renal interstitial fibrosis, and renal collagen III mRNA expression revealed a significant improvement of all parameters in MWF-6(SHR) compared with MWF (P < 0.05). At 32 wk, MWF but not MWF-6(SHR) demonstrated overt proteinuria (354.6 +/- 37.6 versus 48.8 +/- 13.2; P < 0.0001), whereas serum urea, cholesterol, and triglyceride concentrations were lower and creatinine clearance was higher in MWF-6(SHR) compared with MWF (P < 0.05). Therefore, although albuminuria in MWF is determined by a complex interplay of several QTL, our data demonstrate that genetic exchange of one locus on RNO6 leads to marked suppression of early-onset albuminuria and renal damage in MWF.

Albuminuria↗