scholarly journals Genomic Structure and Variation of Nuclear Factor (Erythroid-Derived 2)-Like 2

2013 ◽  
Vol 2013 ◽  
pp. 1-24 ◽  
Author(s):  
Hye-Youn Cho
Keyword(s):  
Complex Traits ◽  
Genomic Structure ◽  
Inbred Mouse ◽  
High Density ◽  
Mouse Strains ◽  
Sequencing Analysis ◽  
Nuclear Factor ◽  
Genetic Characteristics ◽  
Density Mapping ◽  
Wide Range

High-density mapping of mammalian genomes has enabled a wide range of genetic investigations including the mapping of polygenic traits, determination of quantitative trait loci, and phylogenetic comparison. Genome sequencing analysis of inbred mouse strains has identified high-density single nucleotide polymorphisms (SNPs) for investigation of complex traits, which has become a useful tool for biomedical research of human disease to alleviate ethical and practical problems of experimentation in humans. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) encodes a key host defense transcription factor. This review describes genetic characteristics of humanNRF2and its homologs in other vertebrate species.NRF2is evolutionally conserved and shares sequence homology among species. Compilation of publically available SNPs and other genetic mutations shows that humanNRF2is highly polymorphic with a mutagenic frequency of 1 per every 72 bp. Functional at-risk alleles and haplotypes have been demonstrated in various human disorders. In addition, other pathogenic alterations including somatic mutations and misregulated epigenetic processes inNRF2have led to oncogenic cell survival. Comprehensive information from the current review addresses association ofNRF2variation and disease phenotypes and supports the new insights into therapeutic strategies.

scholarly journals Reciprocal F1 hybrids of two inbred mouse strains reveal parent-of-origin and perinatal diet effects on behavior and expression

2018 ◽  
Author(s):  
Daniel Oreperk ◽  
Sarah A Schoenrock ◽  
Rachel McMullan ◽  
Robin Ervin ◽  
Joseph Farrington ◽  
...  
Keyword(s):  
Complex Traits ◽  
Detection System ◽  
Inbred Mouse ◽  
F1 Hybrids ◽  
Hybrid Population ◽  
Psychiatric Disease ◽  
Mouse Strains ◽  
Imprinted Genes ◽  
F1 Hybrid ◽  
Parent Of Origin

ABSTRACTParent-of-origin effects (POEs) in mammals typically arise from maternal effects or from imprinting. Mutations in imprinted genes have been associated with psychiatric disorders, as well as with changes in a handful of animal behaviors. Nonetheless, POEs on complex traits such as behavior remain largely uncharacterized. Furthermore, although perinatal environmental exposures, such as nutrient deficiency, are known to modify both behavior and epigenetic effects generally, the architecture of environment-by-POE is almost completely unexplored. To study POE and environment-by-POE, we employ a relatively neglected but maximally powerful POE-detection system: a reciprocal F1 hybrid population. We exposed female NOD/ShiLtJxC57Bl/6J and C57Bl/6JxNOD/ShiLtJ mice, in utero, to one of four different diets, then after weaning recorded their whole-brain gene expression, as well as a set of behaviors that model psychiatric disease. Microarray expression data revealed an imprinting-enriched set of over a dozen genes subject to POE; the POE on the most significantly affected gene, Carmil1 (a.k.a. Lrrc16a), was validated using qPCR in the same and in a new set of mice. Several behaviors, especially locomotor behaviors, also showed POE. Interestingly, Bayesian mediation analysis suggests Carmil1 expression suppresses behavioral POE, and Airn suppresses POE on Carmil1 expression. A significant diet-by-POE was observed on one behavior, one imprinted gene, and over a dozen non-imprinted genes. Beyond our particular results, our study demonstrates a reciprocal F1 hybrid framework for studying POE and environment-by-POE on behavior.

Abstract 268: Strain-specific Cardiac Fibroblast Response to Isoproterenol-induced Cardiac Fibrosis

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Shuin Park ◽  
Sara Ranjbarvaziri ◽  
Fides Lay ◽  
Peng Zhao ◽  
Aldons J Lusis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Expression Profiles ◽  
Inbred Mouse ◽  
Gene Expression Profiles ◽  
Mouse Strains ◽  
Sequencing Analysis ◽  
Different Strains

Fibroblasts are a heterogeneous population of cells that function within the injury response mechanisms across various tissues. Despite their importance in pathophysiology, the effects of different genetic backgrounds on fibroblast contribution to the development of disease has yet to be addressed. It has previously been shown that mice in the Hybrid Mouse Diversity Panel, which consists of 110 inbred mouse strains, display a spectrum in severity of cardiac fibrosis in response to chronic treatment of isoproterenol (ISO). Here, we characterized cardiac fibroblasts (CFbs) from three different mouse strains (C57BL/6J, C3H/HeJ, and KK/HIJ) which exhibited varying degrees of fibrosis after ISO treatment. The select strains of mice underwent sham or ISO treatment via intraperitoneally-implanted osmotic pumps for 21 days. Masson’s Trichrome staining showed significant differences in fibrosis in response to ISO, with KK/HIJ mice demonstrating the highest levels, C3H/HeJ exhibiting milder levels, and C57BL/6J demonstrating little to no fibrosis. When CFbs were isolated and cultured from each strain, the cells demonstrated similar traits at the basal level but responded to ISO stimuli in a strain-specific manner. Likewise, CFbs demonstrated differential behavior and gene expression in vivo in response to ISO. ISO treatment caused CFbs to proliferate similarly across all strains, however, immunofluorescence staining showed differential levels of CFb activation. Additionally, RNA-sequencing analysis revealed unique gene expression profiles of all three strains upon ISO treatment. Our study depicts the phenotypic heterogeneity of CFbs across different strains of mice and our results suggest that ISO-induced cardiac fibrosis is a complex process that is independent of fibroblast proliferation and is mainly driven by the activation/inhibition of genes involved in pro-fibrotic pathways.

scholarly journals Ultra-High-Density QTL Marker Mapping for Seedling Photomorphogenesis Mediating Arabidopsis Establishment in Southern Patagonia

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel Matsusaka ◽  
Daniele Filiault ◽  
Diego H. Sanchez ◽  
Javier F. Botto
Keyword(s):  
Complex Traits ◽  
Red Light ◽  
High Density ◽  
Potential Candidate ◽  
Hypocotyl Length ◽  
Light Responses ◽  
Wide Range ◽  
Southern Patagonia ◽  
Ril Population ◽  
Wild Accessions

Arabidopsis thaliana shows a wide range of genetic and trait variation among wild accessions. Because of its unparalleled biological and genomic resources, Arabidopsis has a high potential for the identification of genes underlying ecologically important complex traits, thus providing new insights on genome evolution. Previous research suggested that distinct light responses were crucial for Arabidopsis establishment in a peculiar ecological niche of southern Patagonia. The aim of this study was to explore the genetic basis of contrasting light-associated physiological traits that may have mediated the rapid adaptation to this new environment. From a biparental cross between the photomorphogenic contrasting accessions Patagonia (Pat) and Columbia (Col-0), we generated a novel recombinant inbred line (RIL) population, which was entirely next-generation sequenced to achieve ultra-high-density saturating molecular markers resulting in supreme mapping sensitivity. We validated the quality of the RIL population by quantitative trait loci (QTL) mapping for seedling de-etiolation, finding seven QTLs for hypocotyl length in the dark and continuous blue light (Bc), continuous red light (Rc), and continuous far-red light (FRc). The most relevant QTLs, Rc1 and Bc1, were mapped close together to chromosome V; the former for Rc and Rc/dark, and the latter for Bc, FRc, and dark treatments. The additive effects of both QTLs were confirmed by independent heterogeneous inbred families (HIFs), and we explored TZP and ABA1 as potential candidate genes for Rc1 and Bc1QTLs, respectively. We conclude that the Pat × Col-0 RIL population is a valuable novel genetic resource to explore other adaptive traits in Arabidopsis.

scholarly journals Enhanced VWF biosynthesis and elevated plasma VWF due to a natural variant in the murine Vwf gene

Blood ◽  
2006 ◽  
Vol 108 (9) ◽  
pp. 3061-3067 ◽  
Author(s):  
Heidi L. Lemmerhirt ◽  
Jordan A. Shavit ◽  
Gallia G. Levy ◽  
Suzanne M. Cole ◽  
Jeffrey C. Long ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Inbred Mice ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Genetic Modifiers ◽  
Wide Range ◽  
Natural Variant ◽  
Vitro Analysis

Abstract Both genetic and environmental influences contribute to the wide variation in plasma von Willebrand factor (VWF) levels observed in humans. Inbred mouse strains also have highly variable plasma VWF levels, providing a convenient model in which to study genetic modifiers of VWF. Previously, we identified a major modifier of VWF levels in the mouse (Mvwf1) as a regulatory mutation in murine Galgt2. We now report the identification of an additional murine VWF modifier (Mvwf2). Mvwf2 accounts for approximately 16% of the 8-fold plasma VWF variation (or ∼ 25% of the genetic variation) observed between the A/J and CASA/RkJ strains and maps to the murine Vwf gene itself. Twenty SNPs were identified within the coding regions of the A/J and CASA/RkJ Vwf alleles, and in vitro analysis of recombinant VWF demonstrated that a single SNP (+7970G>A) and the associated nonsynonymous amino acid change (R2657Q) confers a significant increase in VWF biosynthesis from the CASA/RkJ Vwf allele. This change appears to represent a unique gain of function that likely explains the mechanism of Mvwf2 in vivo. The identification of a natural Vwf gene variant among inbred mice affecting biosynthesis suggests that similar genetic variation may contribute to the wide range of VWF levels observed in humans.

Behavioral, physiological, and molecular differences in response to dietary restriction in three inbred mouse strains

2006 ◽  
Vol 291 (3) ◽  
pp. E574-E581 ◽  
Author(s):  
Cigdem Gelegen ◽  
David A. Collier ◽  
Iain C. Campbell ◽  
Hugo Oppelaar ◽  
Martien J. H. Kas
Keyword(s):  
Locomotor Activity ◽  
Body Temperature ◽  
Complex Traits ◽  
Food Restriction ◽  
Inbred Mouse ◽  
Behavioral Thermoregulation ◽  
Mouse Strains ◽  
Energy Regulation ◽  
Inbred Mouse Strains ◽  
Brown Adipose

Food restriction paradigms are widely used in animal studies to investigate systems involved in energy regulation. We have observed behavioral, physiological, and molecular differences in response to food restriction in three inbred mouse strains, C57BL/6J, A/J, and DBA/2J. These are the progenitors of chromosome substitution and recombinant inbred mouse strains used for mapping complex traits. DBA/2J and A/J mice increased their locomotor activity during food restriction, and both displayed a decrease in body temperature, but the decrease was significantly larger in DBA/2J compared with A/J mice. C57BL/6J mice did not increase their locomotor activity and displayed a large decrease in their body temperature. The large decline in body temperature during food restriction in DBA/2J and C57BL/6J strains was associated with a robust reduction in plasma leptin levels. DBA/2J mice showed a marked decrease in white and brown adipose tissue masses and an upregulation of the antithermogenic hypothalamic neuropeptide Y Y1 receptor. In contrast, A/J mice showed a reduction in body temperature to a lesser extent that may be explained by downregulation of the thermogenic melanocortin 3 receptor and by behavioral thermoregulation as a consequence of their increased locomotor activity. These data indicate that genetic background is an important parameter in controlling an animal's adaptation strategy in response to food restriction. Therefore, mouse genetic mapping populations based on these progenitor lines are highly valuable for investigating mechanisms underlying strain-dependent differences in behavioral physiology that are seen during reduced food availability.

scholarly journals High Throughput Computational Mouse Genetic Analysis

2020 ◽  
Author(s):  
Ahmed Arslan ◽  
Yuan Guan ◽  
Xinyu Chen ◽  
Robin Donaldson ◽  
Wan Zhu ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Mitochondrial Targeting ◽  
Phenotypic Data ◽  
Factors Affecting ◽  
Wide Range ◽  
Allelic Differences

AbstractBackgroundGenetic factors affecting multiple biomedical traits in mice have been identified when GWAS data, which measured responses in panels of inbred mouse strains, was analyzed using haplotype-based computational genetic mapping (HBCGM). Although this method was previously used to analyze one dataset at a time; but now, a vast amount of mouse phenotypic data is now publicly available, which could enable many more genetic discoveries.ResultsHBCGM and a whole genome SNP map covering 43 inbred strains was used to analyze 8300 publicly available datasets of biomedical responses (1.52M individual datapoints) measured in panels of inbred mouse strains. As proof of concept, causative genetic factors affecting susceptibility for eye, metabolic and infectious diseases were identified when structured automated methods were used to analyze the output. One analysis identified a novel genetic effector mechanism; allelic differences within the mitochondrial targeting sequence affected the subcellular localization of a protein. We also found allelic differences within the mitochondrial targeting sequences of many murine and human proteins, and these could affect a wide range of biomedical phenotypes.ImplicationsThese initial results indicate that genetic factors affecting biomedical responses could be identified through analysis of very large datasets, and they provide an early indication of how this type of ‘augmented intelligence’ can facilitate genetic discovery.

scholarly journals Fine Mapping in 94 Inbred Mouse Strains Using a High-Density Haplotype Resource

Genetics ◽  
2010 ◽  
Vol 185 (3) ◽  
pp. 1081-1095 ◽  
Author(s):  
Andrew Kirby ◽  
Hyun Min Kang ◽  
Claire M. Wade ◽  
Chris Cotsapas ◽  
Emrah Kostem ◽  
...  
Keyword(s):  
Fine Mapping ◽  
Inbred Mouse ◽  
High Density ◽  
Mouse Strains ◽  
Inbred Mouse Strains

scholarly journals The Collaborative Cross Graphical Genome

2019 ◽  
Author(s):  
Hang Su ◽  
Ziwei Chen ◽  
Jaytheert Rao ◽  
Maya Najarian ◽  
John Shorter ◽  
...  
Keyword(s):  
Genomic Sequence ◽  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
Reference Population ◽  
Collaborative Cross ◽  
Graph Representation ◽  
Genome Comparison ◽  
Mouse Strains ◽  
Wide Range ◽  
Eukaryotic Genomes

AbstractThe mouse reference is one of the most widely used and accurately assembled mammalian genomes, and is the foundation for a wide range of bioinformatics and genetics tools. However, it represents the genomic organization of a single inbred mouse strain. Recently, inexpensive and fast genome sequencing has enabled the assembly of other common mouse strains at a quality approaching that of the reference. However, using these alternative assemblies in standard genomics analysis pipelines presents significant challenges. It has been suggested that a pangenome reference assembly, which incorporates multiple genomes into a single representation, are the path forward, but there are few standards for, or instances of practical pangenome representations suitable for large eukaryotic genomes. We present a pragmatic graph-based pangenome representation as a genomic resource for the widely-used recombinant-inbred mouse genetic reference population known as the Collaborative Cross (CC) and its eight founder genomes. Our pangenome representation leverages existing standards for genomic sequence representations with backward-compatible extensions to describe graph topology and genome-specific annotations along paths. It packs 83 mouse genomes (8 founders + 75 CC strains) into a single graph representation that captures important notions relating genomes such as identity-by-descent and highly variable genomic regions. The introduction of special anchor nodes with sequence content provides a valid coordinate framework that divides large eukaryotic genomes into homologous segments and addresses most of the graph-based position reference issues. Parallel edges between anchors place variants within a context that facilitates orthogonal genome comparison and visualization. Furthermore, our graph structure allows annotations to be placed in multiple genomic contexts and simplifies their maintenance as the assembly improves. The CC reference pangenome provides an open framework for new tool chain development and analysis.

scholarly journals High-Density Genotypes of Inbred Mouse Strains: Improved Power and Precision of Association Mapping

2015 ◽  
Vol 5 (10) ◽  
pp. 2021-2026 ◽  
Author(s):  
Christoph D. Rau ◽  
Brian Parks ◽  
Yibin Wang ◽  
Eleazar Eskin ◽  
Petr Simecek ◽  
...  
Keyword(s):  
Association Mapping ◽  
Inbred Mouse ◽  
High Density ◽  
Mouse Strains ◽  
Inbred Mouse Strains

scholarly journals Genetic influence on immune phenotype revealed strain-specific variations in peripheral blood lineages

2008 ◽  
Vol 34 (3) ◽  
pp. 304-314 ◽  
Author(s):  
Stefka B. Petkova ◽  
Rong Yuan ◽  
Shirng-Wern Tsaih ◽  
William Schott ◽  
Derry C. Roopenian ◽  
...  
Keyword(s):  
Blood Cell ◽  
Peripheral Blood ◽  
Large Scale ◽  
Immune Cell ◽  
Inbred Mouse ◽  
Strain Differences ◽  
Peripheral Blood Leukocyte ◽  
Mouse Strains ◽  
Cell Populations ◽  
Wide Range

Inbred mouse strains are routinely used as genetically defined animal models for studying a wide assortment of biological and pathological processes, including immune system function. However, no studies have presented large-scale data on the immune cell populations among the inbred strains in physiological conditions. Here we present a systematic, quantitative analysis of peripheral blood cell phenotypes of 30 mouse strains assessed by flow cytometry. This cohort of mice represents a wide range of genetic origins and includes most of the strains used in genetic, physiological, and immunological studies. We evaluated the relative percentages of peripheral blood leukocyte subtypes (lymphocytes, granulocytes, and monocytes) and lymphocyte subpopulations (CD4+ T, CD8+ T, B220+ B, and natural killer cells) of mature (6-mo-old) mice. Our comprehensive study demonstrated: 1) marked differences in the relative proportions of blood cell populations among the strains at this age, 2) considerable variation of each immune trait with more than twofold difference between strains with the highest and the lowest trait values, and 3) haplotype analysis revealed a strong correlation between eosinophil percentage and a single region on chromosome 14 containing two candidate genes. The strain differences described here provide important information for researchers applying immunophenotyping of peripheral blood in immunological and genetic studies. The data from this study are available as part of the Mouse Phenome Database at http://www.jax.org/phenome .

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