scholarly journals The International Mouse Phenotyping Consortium (IMPC): a large-scale functional catalogue of mammalian genes

2020 ◽  
Keyword(s):  
Large Scale ◽  
International Mouse Phenotyping Consortium ◽  
Mammalian Genes

scholarly journals Genetic and Molecular Analysis of Region 88E9;88F2 in Drosophila melanogaster, Including the ear Gene Related to Human Factors Involved in Lineage-Specific Leukemias

Genetics ◽  
2002 ◽  
Vol 160 (3) ◽  
pp. 1051-1065
Author(s):  
Claudia B Zraly ◽  
Yun Feng ◽  
Andrew K Dingwall
Keyword(s):  
Large Scale ◽  
Drosophila Genome ◽  
Embryonic Cells ◽  
Ems Mutagenesis ◽  
Recessive Lethal ◽  
Protein Levels ◽  
Late Embryogenesis ◽  
Complementation Groups ◽  
Mammalian Genes ◽  
Map Location

Abstract We identified and characterized the Drosophila gene ear (ENL/AF9-related), which is closely related to mammalian genes that have been implicated in the onset of acute lymphoblastic and myelogenous leukemias when their products are fused as chimeras with those of human HRX, a homolog of Drosophila trithorax. The ear gene product is present in all early embryonic cells, but becomes restricted to specific tissues in late embryogenesis. We mapped the ear gene to cytological region 88E11-13, near easter, and showed that it is deleted by Df(3R)ea5022rx1, a small, cytologically invisible deletion. Annotation of the completed Drosophila genome sequence suggests that this region might contain as many as 26 genes, most of which, including ear, are not represented by mutant alleles. We carried out a large-scale noncom-plementation screen using Df(3R)ea5022rx1 and chemical (EMS) mutagenesis from which we identified sevenc novel multi-allele recessive lethal complementation groups in this region. An overlapping deficiency, Df(3R)Po4, allowed us to map several of these groups to either the proximal or the distal regions of Df(3R)ea5022rx1. One of these complementation groups likely corresponds to the ear gene as judged by map location, terminal phenotype, and reduction of EAR protein levels.

scholarly journals The effects of microchipping C57BL/6N mice on standard phenotyping tests

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 20
Author(s):  
R.S. Bains ◽  
H.L. Cater ◽  
M. Stewart ◽  
C.L. Scudamore ◽  
S.E. Wells
Keyword(s):  
Large Scale ◽  
Home Cage ◽  
Histopathological Examination ◽  
Genetic Research ◽  
Inbred Lines ◽  
Null Alleles ◽  
Biologically Relevant ◽  
International Mouse Phenotyping Consortium ◽  
Analysis System ◽  
The Impact

The C57BL/6N inbred lines of mice are widely used in genetic research. They are particularly favoured in large scale studies such as the International Mouse Phenotyping Consortium (IMPC), where C57BL/6N mice are genetically altered to generate a collection of null alleles (currently more than 8500 null alleles have been generated). In this project, mice carrying null alleles are subjected to a pipeline of broad-based phenotyping tests to produce wide ranging phenotyping data on each model. We have previously described the development of a Home Cage Analysis system that automatically tracks the activity of group housed mice from a microchip inserted in the groin. This platform allows assessment of multiple biologically relevant phenotypes over long periods of time without experimenter interference, and therefore is particularly suited for high through-put studies. To investigate the impact of microchips on other tests carried out in the IMPC pipeline, we inserted microchips in 12 male and 12 female C57BL/6Ntac mice at seven weeks of age. Starting at nine weeks of age these mice underwent standard phenotyping tests, concurrently with 20 unchipped C57BL/6Ntac mice (10 females, 10 males). Tissues from a subset of the microchipped mice (six males and six females), chosen at random, were also sent for histopathological examination at the end of the phenotyping pipeline.

scholarly journals A big-data approach to understanding metabolic rate and response to obesity in laboratory mice

2019 ◽  
Author(s):  
June K. Corrigan ◽  
Deepti Ramachandran ◽  
Yuchen He ◽  
Colin Palmer ◽  
Michael J. Jurczak ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Indirect Calorimetry ◽  
Large Scale ◽  
Laboratory Mice ◽  
Phenotypic Analysis ◽  
Metabolic Phenotypes ◽  
International Mouse Phenotyping Consortium ◽  
Housing Temperature ◽  
Genetic And Environmental Factors

AbstractMaintaining a healthy body weight requires an exquisite balance between energy intake and energy expenditure. In humans and in laboratory mice these factors are experimentally measured by powerful and sensitive indirect calorimetry devices. To understand the genetic and environmental factors that contribute to the regulation of body weight, an important first step is to establish the normal range of metabolic values and primary sources contributing to variability in results. Here we examine indirect calorimetry results from two experimental mouse projects, the Mouse Metabolic Phenotyping Centers and International Mouse Phenotyping Consortium to develop insights into large-scale trends in mammalian metabolism. Analysis of nearly 10,000 wildtype mice revealed that the largest experimental variances are consequences of institutional site. This institutional effect on variation eclipsed those of housing temperature, body mass, locomotor activity, sex, or season. We do not find support for the claim that female mice have greater metabolic variation than male mice. An analysis of these factors shows a normal distribution for energy expenditure in the phenotypic analysis of 2,246 knockout strains and establishes a reference for the magnitude of metabolic changes. Using this framework, we examine knockout strains with known metabolic phenotypes. We compare these effects with common environmental challenges including age, and exercise. We further examine the distribution of metabolic phenotypes exhibited by knockout strains of genes corresponding to GWAS obesity susceptibility loci. Based on these findings, we provide suggestions for how best to design and conduct energy balance experiments in rodents, as well as how to analyze and report data from these studies. These recommendations will move us closer to the goal of a centralized physiological repository to foster transparency, rigor and reproducibility in metabolic physiology experimentation.

Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development

Development ◽  
2000 ◽  
Vol 127 (8) ◽  
pp. 1737-1749 ◽  
Author(s):  
M.S. Ko ◽  
J.R. Kitchen ◽  
X. Wang ◽  
T.A. Threat ◽  
X. Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Developmental Disorders ◽  
Large Scale ◽  
Expression Patterns ◽  
Mammalian Development ◽  
Mouse Development ◽  
New Genes ◽  
Entry Points ◽  
Preimplantation Mouse ◽  
Mammalian Genes

Little is known about gene action in the preimplantation events that initiate mammalian development. Based on cDNA collections made from each stage from egg to blastocyst, 25438 3′-ESTs were derived, and represent 9718 genes, half of them novel. Thus, a considerable fraction of mammalian genes is dedicated to embryonic expression. This study reveals profound changes in gene expression that include the transient induction of transcripts at each stage. These results raise the possibility that development is driven by the action of a series of stage-specific expressed genes. The new genes, 798 of them placed on the mouse genetic map, provide entry points for analyses of human and mouse developmental disorders.

Natural antisense transcripts: sound or silence?

2005 ◽  
Vol 23 (2) ◽  
pp. 125-131 ◽  
Author(s):  
Andreas Werner ◽  
Ariane Berdal
Keyword(s):  
Antisense Rna ◽  
Large Scale ◽  
Regulatory Mechanism ◽  
Antisense Transcription ◽  
Antisense Transcripts ◽  
Naturally Occurring ◽  
Mammalian Genes ◽  
Gene Regulatory ◽  
Regulatory Potential ◽  
To Come

Antisense RNA was a rather uncommon term in a physiology environment until short interfering RNAs emerged as the tool of choice to knock down the expression of specific genes. As a consequence, the concept of RNA having regulatory potential became widely accepted. Yet, there is more to come. Computational studies suggest that between 15 and 25% of mammalian genes overlap, giving rise to pairs of sense and antisense RNAs. The resulting transcripts potentially interfere with each other’s processing, thus representing examples of RNA-mediated gene regulation by endogenous, naturally occurring antisense transcripts. Concerns that the large-scale antisense transcription may represent transcriptional noise rather than a gene regulatory mechanism are strongly opposed by recent reports. A relatively small, well-defined group of antisense or noncoding transcripts is linked to monoallelic gene expression as observed in genomic imprinting, X chromosome inactivation, and clonal expression of B and T leukocytes. For the remaining, much larger group of bidirectionally transcribed genes, however, the physiological consequences of antisense transcription as well as the cellular mechanism(s) involved remain largely speculative.

scholarly journals The effects of microchipping C57BL/6N mice on standard phenotyping tests

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 20
Author(s):  
R.S. Bains ◽  
H.L. Cater ◽  
M. Stewart ◽  
C.L. Scudamore ◽  
S.E. Wells
Keyword(s):  
Large Scale ◽  
Histopathological Examination ◽  
Genetic Research ◽  
Density Measurement ◽  
Null Alleles ◽  
Mineral Density ◽  
Biologically Relevant ◽  
International Mouse Phenotyping Consortium ◽  
Analysis System ◽  
The Impact

The C57BL/6N inbred lines of mice are widely used in genetic research. They are particularly favoured in large scale studies such as the International Mouse Phenotyping Consortium (IMPC), where C57BL/6N mice are genetically altered to generate a collection of null alleles (currently more than 8500 null alleles have been generated). In this project, mice carrying null alleles are subjected to a pipeline of broad-based phenotyping tests to produce wide ranging phenotyping data on each model. We have previously described the development of a Home Cage Analysis system that automatically tracks the activity of group housed mice from a microchip inserted in the groin. This platform allows assessment of multiple biologically relevant phenotypes over long periods of time without experimenter interference, and therefore is particularly suited for high through-put studies. To investigate the impact of microchips on other tests carried out in the IMPC pipeline, we inserted microchips in 12 male and 12 female C57BL/6Ntac mice at seven weeks of age. Starting at nine weeks of age these mice underwent standard phenotyping tests, concurrently with 20 unchipped C57BL/6Ntac mice (10 females, 10 males). Tissues from a subset of the microchipped mice (six males and six females), chosen at random, were also sent for histopathological examination at the end of the phenotyping pipeline. No significant impact of insertion of microchip was observed in any of the phenotyping tests apart from bone mineral density measurement at DEXA due to the nature of the microchip. We therefore recommend that the microchip be inserted during the DEXA procedure, after the measurement is taken but before the mouse has recovered from the anaesthetic. This would avoid multiple anaesthetic exposures and prevent the potential variability in DEXA analysis output.

scholarly journals Soft windowing application to improve analysis of high-throughput phenotyping data

2019 ◽  
Vol 36 (5) ◽  
pp. 1492-1500 ◽  
Author(s):  
Hamed Haselimashhadi ◽  
Jeremy C Mason ◽  
Violeta Munoz-Fuentes ◽  
Federico López-Gómez ◽  
Kolawole Babalola ◽  
...  
Keyword(s):  
High Throughput ◽  
Large Scale ◽  
Methodological Approach ◽  
R Package ◽  
Supplementary Information ◽  
Complex Data ◽  
Control Data ◽  
International Mouse Phenotyping Consortium ◽  
High Throughput Phenotyping ◽  
The Uk

Abstract Motivation High-throughput phenomic projects generate complex data from small treatment and large control groups that increase the power of the analyses but introduce variation over time. A method is needed to utlize a set of temporally local controls that maximizes analytic power while minimizing noise from unspecified environmental factors. Results Here we introduce ‘soft windowing’, a methodological approach that selects a window of time that includes the most appropriate controls for analysis. Using phenotype data from the International Mouse Phenotyping Consortium (IMPC), adaptive windows were applied such that control data collected proximally to mutants were assigned the maximal weight, while data collected earlier or later had less weight. We applied this method to IMPC data and compared the results with those obtained from a standard non-windowed approach. Validation was performed using a resampling approach in which we demonstrate a 10% reduction of false positives from 2.5 million analyses. We applied the method to our production analysis pipeline that establishes genotype–phenotype associations by comparing mutant versus control data. We report an increase of 30% in significant P-values, as well as linkage to 106 versus 99 disease models via phenotype overlap with the soft-windowed and non-windowed approaches, respectively, from a set of 2082 mutant mouse lines. Our method is generalizable and can benefit large-scale human phenomic projects such as the UK Biobank and the All of Us resources. Availability and implementation The method is freely available in the R package SmoothWin, available on CRAN http://CRAN.R-project.org/package=SmoothWin. Supplementary information Supplementary data are available at Bioinformatics online.

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