Identification of a major locus for islet inflammation and fibrosis in the spontaneously diabetic Torii rat

The pathogenesis of inflammation and fibrosis in the pancreatic islets in diabetes is largely unknown. Spontaneously diabetic Torii (SDT) rats exhibit inflammation and fibrosis in and around the islets during the development of the disease. We investigated genetic factors for diabetes, islet inflammation, and fibrosis in the SDT rat. We produced F1 and F2 rats by intercross between SDT and F344 rats, examined the onset of diabetes, glucose tolerance, and histology of the pancreas, and performed genetic analysis of these traits. We then established a congenic strain carrying the SDT allele at the strongest diabetogenic locus on the F344 genetic background and characterized glucose tolerance and histology of the pancreas. F1 rats showed glucose intolerance and inflammatory changes mainly in the islets. Genetic analysis of diabetes identified a major locus on chromosome 3, designated Dmsdt1, at which a dominantly acting SDT allele was involved. Quantitative trait locus (QTL) analysis of glucose tolerance revealed, in addition to Dmsdt1 [logarithm of odds (LOD) 5.3 near D3Mit12], three other loci, designated Dmsdt2 (LOD 4.2 at D8Rat46), Dmsdt3 (LOD 3.8 near D13Arb5), and Dmsdt4 (LOD 5.8 at D14Arb18). Analysis of a congenic strain for Dmsdt1 indicates that the dominantly acting SDT allele induces islet inflammation and fibrosis. Thus we have found a major locus on chromosome 3 for islet inflammation and fibrosis in the SDT rat. Identification of the genes responsible should provide insight into the pathogenesis of diabetes.

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NOD2 Mutation-Associated Case with Blau Syndrome Triggered by BCG Vaccination

Children ◽

10.3390/children8020117 ◽

2021 ◽

Vol 8 (2) ◽

pp. 117

Author(s):

Akiko Arakawa ◽

Naotomo Kambe ◽

Ryuta Nishikomori ◽

Akiyo Tanabe ◽

Masamichi Ueda ◽

...

Keyword(s):

Genetic Analysis ◽

Topical Corticosteroid ◽

Genetic Background ◽

Skin Lesions ◽

Blau Syndrome ◽

Nod2 Mutation ◽

Bcg Vaccination ◽

Cystic Tumors ◽

Ophthalmologic Examination ◽

Inflammatory Changes

We describe a patient who developed multiple granulomatous skin lesions after Bacille de Calmette et Guérin (BCG) vaccination without significant effect by topical corticosteroid, followed by painless cystic tumors on the bilateral knees and hands and inflammatory changes on ophthalmologic examination. A functional mutation in NOD2 was detected by a genetic analysis, and he was diagnosed as sporadic Blau syndrome. Since NOD2 acts as a sensor for the BCG component, it is possible that BCG vaccination may trigger granuloma formation in Blau syndrome patients with such genetic background.

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Genetics of Differences in Pheromonal Hydrocarbons Between Drosophila melanogaster and D. simulans

Genetics ◽

10.1093/genetics/143.1.353 ◽

1996 ◽

Vol 143 (1) ◽

pp. 353-364 ◽

Cited By ~ 3

Author(s):

Jerry A Coyne

Keyword(s):

Drosophila Melanogaster ◽

Sexual Dimorphism ◽

Genetic Analysis ◽

Species Difference ◽

The Other ◽

Chromosome 3 ◽

Apparent Effect ◽

The Third ◽

Hydrocarbon Profile ◽

The Right

Abstract Females of Drosophila melanogaster and its sibling species D. simulans have very different cuticular hydrocarbons, with the former bearing predominantly 7,11-heptacosadiene and the latter 7-tricosene. This difference contributes to reproductive isolation between the species. Genetic analysis shows that this difference maps to only the third chromosome, with the other three chromosomes having no apparent effect. The D. simulans alleles on the left arm of chromosome 3 are largely recessive, allowing us to search for the relevant regions using D. melanogaster deficiencies. At least four nonoverlapping regions of this arm have large effects on the hydrocarbon profile, implying that several genes on this arm are responsible for the species difference. Because the right arm of chromosome 3 also affects the hydrocarbon profile, a minimum of five genes appear to be involved. The large effect of the third chromosome on hydrocarbons has also been reported in the hybridization between D. simulans and its closer relative D. sechellia, implying either an evolutionaly convergence or the retention in D. sechllia of an ancestral sexual dimorphism.

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Quantitative trait loci mapping for cholesterol gallstones in AKR/J and C57L/J strains of mice

Physiological Genomics ◽

10.1152/physiolgenomics.2000.4.1.59 ◽

2000 ◽

Vol 4 (1) ◽

pp. 59-65 ◽

Cited By ~ 58

Author(s):

BEVERLY PAIGEN ◽

NICHOLAS J. SCHORK ◽

KAREN L. SVENSON ◽

YIN-CHAI CHEAH ◽

JIAN-LONG MU ◽

...

Keyword(s):

Quantitative Trait ◽

Congenic Strain ◽

Cholesterol Gallstone ◽

Gallstone Disease ◽

Gallstone Formation ◽

Quantitative Trait Loci Mapping ◽

Cholesterol Gallstones ◽

Lithogenic Diet ◽

The Difference ◽

Trait Locus

Quantitative trait locus (QTL) mapping was used to locate genes that determine the difference in cholesterol gallstone disease between the gallstone-susceptible strain C57L/J and the gallstone-resistant strain AKR/J. Gallstone weight was determined in 231 male (AKR × C57L) F1× AKR backcross mice fed a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% butterfat for 8 wk. Mice having no stones and mice having the largest stones were genotyped at ∼20-cM intervals to find the loci determining cholesterol gallstone formation. The major locus, Lith1, mapped near D2Mit56 and was confirmed by constructing a congenic strain, AK.L- Lith1s. Another locus, Lith2, mapped near D19Mit58 and was also confirmed by constructing a congenic strain AK.L- Lith2s. Other suggestive, but not statistically significant, loci mapped to chromosomes 6, 7, 8, 10, and X. The identification of these Lith genes will elucidate the pathophysiology of cholesterol gallstone formation.

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SINE jumping contributes to large-scale polymorphisms in the pig genomes

10.21203/rs.3.rs-352249/v1 ◽

2021 ◽

Author(s):

Cai Chen ◽

Enrico D'Alessandro ◽

Eduard Murani ◽

Yao Zheng ◽

Domenico Giosa ◽

...

Keyword(s):

Genetic Analysis ◽

Population Genetic ◽

Large Scale ◽

Structural Variations ◽

Population Genetic Analysis ◽

Protein Coding ◽

Pig Breeds ◽

A Genome ◽

Trait Locus ◽

And Cluster Analysis

Abstract Background: Molecular markers based on retrotransposon insertion polymorphisms (RIPs) have been developed and are widely used in plants and animals. Short interspersed nuclear elements (SINEs) exert wide impacts on gene activity and even on phenotypes. However, SINE RIP profiles in livestock remain largely unknown, and not be revealed in pigs. Results: Our data revealed that SINEA1 displayed the most polymorphic insertions (22.5% intragenic and 26.5% intergenic), followed by SINEA2 (10.5% intragenic and 9% intergenic) and SINEA3 (12.5% intragenic and 5.0% intergenic). We developed a genome-wide SINE RIP mining protocol and obtained a large number of SINE RIPs (36,284), with over 80% accuracy and an even distribution in chromosomes (14.5/Mb), and 74.34% of SINE RIPs generated by SINEA1 element. Over 65% of pig SINE RIPs overlap with genes, with significant enrichment in the first and second introns of protein-coding and long non-coding RNA genes. Nearly half of the RIPs are common in these pig breeds. Sixteen SINE RIPs were applied for population genetic analysis in 23 pig breeds, the phylogeny tree and cluster analysis were generally consistent with the geographical distributions of native pig breeds in China. Conclusions: Our analysis revealed that SINEA1–3 elements, particularly SINEA1, are high polymorphic across different pig breeds, and generate large-scale structural variations in the pig genomes. And over 35, 000 SINE RIP markers were obtained. These data indicate that young SINE elements play important roles in creating new genetic variations and shaping the evolution of pig genome, and also provide strong evidences to support the great potential of SINE RIPs as genetic markers, which can be used for population genetic analysis and quantitative trait locus (QTL) mapping in pig.

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The control of trichome spacing and number in Arabidopsis

Development ◽

10.1242/dev.122.3.997 ◽

1996 ◽

Vol 122 (3) ◽

pp. 997-1005 ◽

Cited By ~ 17

Author(s):

J.C. Larkin ◽

N. Young ◽

M. Prigge ◽

M.D. Marks

Keyword(s):

Minimum Distance ◽

Cell Lineage ◽

Clonal Analysis ◽

Chromosome 2 ◽

Major Locus ◽

Cell Lineages ◽

Trichome Development ◽

Spacing Pattern ◽

Trait Locus ◽

Locus Mapping

Arabidopsis trichomes are single-celled epidermal hairs that serve as a useful model for the study of plant cell differentiation. An examination of the distribution of trichomes early in their development revealed that developing trichomes occur adjacent to another trichome much less frequently than would be expected by chance. Clonal analysis of epidermal cell lineages ruled out a role for cell lineage in generating the observed minimum-distance spacing pattern. Taken together, these results are consistent with a role for lateral inhibition in the control of trichome development. We also report the identification of a new locus, Reduced Trichome Number (RTN), which affects the initiation of trichomes. This locus was initially detected by the reduced number of leaf trichomes on Landsberg erecta plants compared to that on Columbia plants. Quantitative Trait Locus mapping revealed that more than 73% of the variation in trichome number was due to a major locus near erecta on chromosome 2. The reduced number of trichomes conditioned by the Landsberg erecta allele of this locus appeared to be due to an early cessation of trichome initiation. The implications of these observations are discussed with regard to previously published models of trichome development.

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Complete and overlapping congenics proving the existence of a quantitative trait locus for blood pressure on Dahl rat chromosome 17

Physiological Genomics ◽

10.1152/physiolgenomics.00275.2004 ◽

2005 ◽

Vol 21 (1) ◽

pp. 112-116 ◽

Cited By ~ 19

Author(s):

Myrian Grondin ◽

Vasiliki Eliopoulos ◽

Raphaelle Lambert ◽

Yishu Deng ◽

Anita Ariyarajah ◽

...

Keyword(s):

Blood Pressure ◽

Quantitative Trait Locus ◽

Quantitative Trait ◽

Congenic Strain ◽

Chromosome 17 ◽

Congenic Strains ◽

Genome Wide ◽

A Genome ◽

Trait Locus ◽

Negative Controls

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 < 0.04) than that of DSS rats. In contrast, BPs of C17S.L3, C17S.L4, and C17S.L5 were not different ( 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.

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

Physiological Genomics ◽

10.1152/physiolgenomics.00080.2001 ◽

2002 ◽

Vol 8 (2) ◽

pp. 81-86 ◽

Cited By ~ 38

Author(s):

Michael R. Garrett ◽

John P. Rapp

Keyword(s):

Blood Pressure ◽

Quantitative Trait Locus ◽

Quantitative Trait ◽

Congenic Strain ◽

Major Effect ◽

Large Region ◽

Chromosome 5 ◽

Low Blood Pressure ◽

Trait Locus

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.

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Congenic strain confirms putative quantitative trait locus for body weight in the rat

Mammalian Genome ◽

10.1007/s003359900751 ◽

1998 ◽

Vol 9 (4) ◽

pp. 294-296 ◽

Cited By ~ 12

Author(s):

P. Kováqcs ◽

B. Voigt ◽

I. Klöting

Keyword(s):

Quantitative Trait Locus ◽

Body Weight ◽

Quantitative Trait ◽

Congenic Strain ◽

Putative Quantitative Trait Locus ◽

Trait Locus

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Mapping colitis susceptibility in mouse models: distal chromosome 3 contains major loci related to Cdcs1

Physiological Genomics ◽

10.1152/physiolgenomics.00084.2013 ◽

2013 ◽

Vol 45 (20) ◽

pp. 925-930 ◽

Cited By ~ 8

Author(s):

Manuela Buettner ◽

André Bleich

Keyword(s):

Mouse Models ◽

Genetic Mutation ◽

Chromosome 3 ◽

Environmental Interactions ◽

Causative Factors ◽

Distal Chromosome ◽

Pathogen Control ◽

Inflammatory Bowel ◽

Trait Locus ◽

Relevant Factors

Inflammatory bowel disease (IBD) summarizes a group of chronic intestinal disorders with Crohn's disease and ulcerative colitis being most prominent. Though much effort is put into identification of causative factors, its etiology is still not understood. Risk factors for disease development include genetic predisposition and environmental triggers. Crucial for identification and analysis of relevant factors are mouse models. Experimental IBD in mice occurs spontaneously or is induced by chemicals, cell transfer, pathogens, or genetic mutation. These models were utilized for analyzing genetic contribution to disease and genotype-environmental interactions. In these studies, a variety of modifier loci were identified, thereby demonstrating the complexity of disease. A major contribution of distal chromosome 3 was independently replicated in several studies. The first colitogenic QTL in this region was detected using the IL-10-deficient mouse model and called cytokine deficiency-induced colitis susceptibility ( Cdcs) 1. This quantitative trait locus contains at least three subintervals with independent genetic factors. This locus or defined subintervals were replicated in at least seven studies, using models based on dysregulation of innate or adaptive immunity or pathogen control. In this review we illustrate the various models used for genetic mapping of susceptibility to experimental IBD and display Cdcs1-related loci as well as the mechanism of their contribution identified so far.

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