Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Unexpected complexity in the haplotypes of commonly used inbred strains of laboratory mice.

ABSTRACT: Investigation of sequence variation in common inbred mouse strains has revealed a segmented pattern in which regions of high and low variant density are intermixed. Furthermore, it has been suggested that allelic strain distribution patterns also occur in well defined blocks and consequently could be used to map quantitative trait loci (QTL) in comparisons between inbred strains. We report a detailed analysis of polymorphism distribution in multiple inbred mouse strains over a 4.8-megabase region containing a QTL influencing anxiety. Our analysis indicates that it is only partly true that the genomes of inbred strains exist as a patchwork of segments of sequence identity and difference. We show that the definition of haplotype blocks is not robust and that methods for QTL mapping may fail if they assume a simple block-like structure.

SUBMITTER: Yalcin B

PROVIDER: S-EPMC470780 | biostudies-literature | 2004 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Unexpected complexity in the haplotypes of commonly used inbred strains of laboratory mice.

Yalcin B B Fullerton J J Miller S S Keays D A DA Brady S S Bhomra A A Jefferson A A Volpi E E Copley R R RR Flint J J Mott R R

Proceedings of the National Academy of Sciences of the United States of America 20040621 26

Investigation of sequence variation in common inbred mouse strains has revealed a segmented pattern in which regions of high and low variant density are intermixed. Furthermore, it has been suggested that allelic strain distribution patterns also occur in well defined blocks and consequently could be used to map quantitative trait loci (QTL) in comparisons between inbred strains. We report a detailed analysis of polymorphism distribution in multiple inbred mouse strains over a 4.8-megabase regio ...[more]

PMID: 15210992

Similar Datasets

Mild inborn errors of metabolism in commonly used inbred mouse strains.

Project description:Inbred mouse strains are a cornerstone of translational research but paradoxically many strains carry mild inborn errors of metabolism. For example, ?-aminoadipic acidemia and branched-chain ketoacid dehydrogenase deficiency are known in C57BL/6J mice. Using RNA sequencing, we now reveal the causal variants in Dhtkd1 and Bckdhb, and the molecular mechanism underlying these metabolic defects. C57BL/6J mice have decreased Dhtkd1 mRNA expression due to a solitary long terminal repeat (LTR) in intron 4 of Dhtkd1. This LTR harbors an alternate splice donor site leading to a partial splicing defect and as a consequence decreased total and functional Dhtkd1 mRNA, decreased DHTKD1 protein and ?-aminoadipic acidemia. Similarly, C57BL/6J mice have decreased Bckdhb mRNA expression due to an LTR retrotransposon in intron 1 of Bckdhb. This transposable element encodes an alternative exon 1 causing aberrant splicing, decreased total and functional Bckdhb mRNA and decreased BCKDHB protein. Using a targeted metabolomics screen, we also reveal elevated plasma C5-carnitine in 129 substrains. This biochemical phenotype resembles isovaleric acidemia and is caused by an exonic splice mutation in Ivd leading to partial skipping of exon 10 and IVD protein deficiency. In summary, this study identifies three causal variants underlying mild inborn errors of metabolism in commonly used inbred mouse strains.

| S-EPMC6535113 | biostudies-literature

Ebola Virus Infection in Commonly Used Laboratory Mouse Strains.

Project description:The mouse model for Ebola virus (EBOV) is an established and often used animal model for countermeasure development. Although it has its limitations, it recapitulates certain key features of human EBOV disease and principally shows uniform lethality. However, in the recent past, several studies reported surviving animals when evaluating treatment or vaccine approaches. Therefore, we analyzed the severity of disease and lethality of mouse-adapted (MA-) EBOV infection in 6 different mouse strains. We identified outbred CD-1 mice to be the only strain tested resulting in uniform lethality when infected with different doses of MA-EBOV or reverse genetics-generated MA-EBOV. In contrast, infection of different inbred mouse strains resulted in partial survival depending on virus and dose. Of these inbred strains, 129 mice provided the most consistent model. Our study provides a helpful dataset when planning EBOV mouse studies for countermeasure efficacy testing and highlights the limitations of certain mouse strains as EBOV models.

| S-EPMC6249562 | biostudies-literature

Genetic variation in coding regions between and within commonly used inbred rat strains.

Project description:Single nucleotide polymorphisms (SNPs) are the most common genetic variation in mammalian populations. Their significance is illustrated by their potential contribution to common disease but also by their potential for use in genetic association and mapping experiments. We have examined the genetic variation between commonly used inbred rat strains by using an efficient SNP discovery and typing assay based on enzyme-based (CEL I) heteroduplex cleavage. Screening of a panel of 96 different rat (sub-)strains for 100 genomic loci in 55 genes, whose human homologs are implicated in clinically relevant diseases like neurological disorder, cancer, schizophrenia, and obesity, resulted in the identification of 103 novel polymorphisms. As all strains are simultaneously genotyped in this setup, this allowed us to make an estimate of the genetic variation between and within commonly used rat inbred strains. Interestingly, we observed substantial genetic variation between colonies of the same inbred strain, maintained at different locations. Furthermore, we identified 17 non-synonymous SNPs that may have an effect on protein function and contribute to phenotypic differences between different laboratory strains.

| S-EPMC442143 | biostudies-other

Proteomic profiling of two commonly used laboratory yeast strains: W303 and BY4742

Project description:The yeast Saccharomyces cerevisiae is a powerful model system that is often used to expand our understanding of cellular processes and biological functions. Although many genetically well-characterized laboratory strains of S. cerevisiae are available, they may have different genetic backgrounds which can confound data interpretation. Here, we profile and compare the proteomes of two common laboratory yeast background strains, W303 and BY4742, in both exponential and stationary growth phases using isobaric tag-based mass spectrometry. We quantified over 4,400 proteins, hundreds of which showed differences in abundance between strains and/or growth phases. Moreover, we used proteome-wide abundance to profile the mating type of the strains used in the experiment, the auxotrophic markers and associated metabolic pathways, as well as to investigate differences in particular classes of proteins, such as the pleiotropic drug resistance (PDR) proteins. This study is a valuable resource that offers insight into mechanistic differences between two common yeast background strains and can be used as a guide to select a background that is best suited for addressing a particular biological question.

2023-12-28 | PXD044388 | Pride

7 Brain Regions in 20 Inbred Strains of Laboratory Mice

Project description:Survey of gene expression in 7 brain regions at 6-8wks of age in 20 inbred strains of laboratory mice. Autism is a highly heritable neurodevelopmental disorder with no consistent neuropathological hallmarks, diagnosed through behavioral inventory rather than a biomarker. The genetic etiology of autism is complex and likely has a significant interaction with the environment. To investigate the molecular and genetic nature of autism, we modeled the core symptom of social deficits in inbred strains of mice. Using gene expression profiles and behavioral phenotyping relevant to social deficits, we have identified basic cellular functions that may be dysregulated in the brain in autism. Correlations between these two complex datasets indicate cell morphology, proliferation, and migration may be perturbed in disorders of altered social behavior. Furthermore, these data in the mouse show significant overlap with published expression profiling in lymphoblastoid lines from autistic individuals. Keywords: Comparison between inbred strains and brain regions.

2009-02-05 | GSE10415 | GEO

Association of Nrf2 polymorphism haplotypes with acute lung injury phenotypes in inbred strains of mice.

Project description:AimsNrf2 is a master transcription factor for antioxidant response element (ARE)-mediated cytoprotective gene induction. A protective role for pulmonary Nrf2 was determined in model oxidative disorders, including hyperoxia-induced acute lung injury (ALI). To obtain additional insights into the function and genetic regulation of Nrf2, we assessed functional single nucleotide polymorphisms (SNPs) of Nrf2 in inbred mouse strains and tested whether sequence variation is associated with hyperoxia susceptibility.ResultsNrf2 SNPs were compiled from publicly available databases and by re-sequencing DNA from inbred strains. Hierarchical clustering of Nrf2 SNPs categorized the strains into three major haplotypes. Hyperoxia susceptibility was greater in haplotypes 2 and 3 strains than in haplotype 1 strains. A promoter SNP -103 T/C adding an Sp1 binding site in haplotype 2 diminished promoter activation basally and under hyperoxia. Haplotype 3 mice bearing nonsynonymous coding SNPs located in (1862 A/T, His543Gln) and adjacent to (1417 T/C, Thr395Ile) the Neh1 domain showed suppressed nuclear transactivation of pulmonary Nrf2 relative to other strains, and overexpression of haplotype 3 Nrf2 showed lower ARE responsiveness than overexpression of haplotype 1 Nrf2 in airway cells. Importantly, we found a significant correlation of Nrf2 haplotypes and hyperoxic lung injury phenotypes.Innovation and conclusionThe results indicate significant influence of Nrf2 polymorphisms and haplotypes on gene function and hyperoxia susceptibility. Our findings further support Nrf2 as a genetic determinant in ALI pathogenesis and provide useful tools for investigators who use mouse strains classified by Nrf2 haplotypes to elucidate the role for Nrf2 in oxidative disorders.

| S-EPMC4298158 | biostudies-literature

Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains.

Project description:Inbred mouse strains play a critical role in biomedical research. Genetic homogeneity within inbred strains and their general amenability to genetic manipulation have made them an ideal resource for dissecting the physiological function(s) of individual genes. However, the inbreeding that makes inbred mice so useful also results in genetic divergence between them. This genetic divergence is often unaccounted for but may be a confounding factor when comparing studies that have utilized distinct inbred strains. Here, we compared the cardiac function of C57BL/6J mice to seven other commonly used inbred mouse strains: FVB/NJ, DBA/2J, C3H/HeJ, BALB/cJ, 129X1/SvJ, C57BL/10SnJ, and 129S1/SvImJ. The assays used to compare cardiac function were the ex vivo isolated Langendorff heart preparation and in vivo real-time hemodynamic analysis using conductance micromanometry. We report significant strain-dependent differences in cardiac function between C57BL/6J and other commonly used inbred strains. C57BL/6J maintained better cardiac function than most inbred strains after ex vivo ischemia, particularly compared with 129S1/SvImJ, 129X1/SvJ, and C57BL/10SnJ strains. However, during in vivo acute hypoxia 129X1/SvJ and 129S1/SvImJ maintained relatively normal cardiac function, whereas C57BL/6J animals showed dramatic cardiac decompensation. Additionally, C3H/HeJ showed rapid and marked cardiac decompensation in response to esmolol infusion compared with effects of other strains. These findings demonstrate the complex effects of genetic divergence between inbred strains on cardiac function. These results may help inform analysis of gene ablation or transgenic studies and further demonstrate specific quantitative traits that could be useful in discovery of genetic modifiers relevant to cardiac health and disease.

| S-EPMC2957793 | biostudies-literature

Inbred lab mice are not isogenic: genetic variation within inbred strains used to infer the mutation rate per nucleotide site.

Project description:For over a century, inbred mice have been used in many areas of genetics research to gain insight into the genetic variation underlying traits of interest. The generalizability of any genetic research study in inbred mice is dependent upon all individual mice being genetically identical, which in turn is dependent on the breeding designs of companies that supply inbred mice to researchers. Here, we compare whole-genome sequences from individuals of four commonly used inbred strains that were procured from either the colony nucleus or from a production colony (which can be as many as ten generations removed from the nucleus) of a large commercial breeder, in order to investigate the extent and nature of genetic variation within and between individuals. We found that individuals within strains are not isogenic, and there are differences in the levels of genetic variation that are explained by differences in the genetic distance from the colony nucleus. In addition, we employ a novel approach to mutation rate estimation based on the observed genetic variation and the expected site frequency spectrum at equilibrium, given a fully inbred breeding design. We find that it provides a reasonable per nucleotide mutation rate estimate when mice come from the colony nucleus (~7.9 × 10-9 in C3H/HeN), but substantially inflated estimates when mice come from production colonies.

| S-EPMC7852876 | biostudies-literature

sequencing 4 inbred rat strains commonly used to study chronic inflammation.

Project description:Identification of candidate risk gene variations by whole-genome sequence of four rat strains commonly used in inflammation research

| PRJEB5491 | ENA

Statistical distributions commonly used in measurement uncertainty in laboratory medicine.

Project description:Uncertainty is an inseparable part of all types of measurement. Recently, the International Organization for Standardization (ISO) released a new standard (ISO 20914) on how to calculate measurement uncertainty (MU) in laboratory medicine. This standard can be regarded as the beginning of a new era in laboratory medicine. Measurement uncertainty comprises various components and is used to calculate the total uncertainty. All components must be expressed in standard deviation (SD) and then combined. However, the characteristics of these components are not the same; some are expressed as SD, while others are expressed as a ± b, such as the purity of the reagents. All non-SD variables must be transformed into SD, which requires a detailed knowledge of common statistical distributions used in the calculation of MU. Here, the main statistical distributions used in MU calculation are briefly summarized.

| S-EPMC6999182 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data