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The mouse Engrailed genes, En1 and En2, play an important role in the development of the cerebellum from its inception at the mid/hindbrain boundary in early embryonic development through cell type specification events and beyond. In the absence of En1, the cerebellum and caudal midbrain fail to develop normally--a phenotype that we have previously reported to be strain dependent. On the 129/S1 strain background, En1 null alleles lead to mid/hindbrain failure, whereas on the C57BL/6 background, En1 deficiency is compatible with near normal cerebellar development. We have pursued this dramatic effect of genetic background by performing a genetic modifier screen through F1 backcross and F1 intercross matings. The backcross has yielded two strong candidate intervals with suggestive linkage to a third region. Moreover, variations in rescue frequency among subgroups within the backcross indicate gender and parent of origin influences on rescue penetrance. The intercross data reveal locus heterogeneity of the En1 modifiers, with more than one compliment of C57BL/6 and 129/S1 alleles capable of mediating the rescue phenotype. These findings highlight the complexity and plasticity of gene networks involved in brain development.
Pubmed ID: 16884697
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International database for laboratory mouse. Data offered by The Jackson Laboratory includes information on integrated genetic, genomic, and biological data. MGI creates and maintains integrated representation of mouse genetic, genomic, expression, and phenotype data and develops reference data set and consensus data views, synthesizes comparative genomic data between mouse and other mammals, maintains set of links and collaborations with other bioinformatics resources, develops and supports analysis and data submission tools, and provides technical support for database users. Projects contributing to this resource are: Mouse Genome Database (MGD) Project, Gene Expression Database (GXD) Project, Mouse Tumor Biology (MTB) Database Project, Gene Ontology (GO) Project at MGI, and MouseCyc Project at MGI.
View all literature mentionsNext generation sequencing and genotyping services provided to investigators working to discover genes that contribute to disease. On-site statistical geneticists provide insight into analysis issues as they relate to study design, data production and quality control. In addition, CIDR has a consulting agreement with the University of Washington Genetics Coordinating Center (GCC) to provide statistical and analytical support, most predominantly in the areas of GWAS data cleaning and methods development. Completed studies encompass over 175 phenotypes across 530 projects and 620,000 samples. The impact is evidenced by over 380 peer-reviewed papers published in 100 journals. Three pathways exist to access the CIDR genotyping facility: * NIH CIDR Program: The CIDR contract is funded by 14 NIH Institutes and provides genotyping and statistical genetic services to investigators approved for access through competitive peer review. An application is required for projects supported by the NIH CIDR Program. * The HTS Facility: The High Throughput Sequencing Facility, part of the Johns Hopkins Genetic Resources Core Facility, provides next generation sequencing services to internal JHU investigators and external scientists on a fee-for-service basis. * The JHU SNP Center: The SNP Center, part of the Johns Hopkins Genetic Resources Core Facility, provides genotyping to internal JHU investigators and external scientists on a fee-for-service basis. Data computation service is included to cover the statistical genetics services provided for investigators seeking to identify genes that contribute to human disease. Human Genotyping Services include SNP Genome Wide Association Studies, SNP Linkage Scans, Custom SNP Studies, Cancer Panel, MHC Panels, and Methylation Profiling. Mouse Genotyping Services include SNP Scans and Custom SNP Studies.
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