International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Oakey R J
Department of Medical & molecular Genetics, GKT School of Medicine, London, SE1 9RT, UK

Co-Authors: 2) Underkoffler L A, 2) Collins J N, 3) Beechey C V, 1) Choi J D
Institutions: 1) Department of Medical & molecular Genetics, GKT School of Medicine, London, SE1 9RT, UK, 2) Division of Human Genetics, The Children's Hospital of Philadelphia, PA 19104, USA, 3) Mammalian Genetics Unit, Harwell, Didcot, Oxon OX11 ORD, UK

Imprinted genes are differentially expressed from the maternally and paternally inherited alleles. Accordingly, uniparental inheritance of an imprinted chromosome or region leads to the mis-expression of imprinted genes. Mouse stocks carrying Robertsonian and reciprocal translocations for chromosomes 7, 11, & 18 have generated embryos with uniparental disomy or partial chromosome uniparental duplications. RNAs from these mice have been used to query DNA microarrays. A computer-based screen has reduced false positives by map location to provide a systematic approach to novel imprinted gene identification. (1) Most of the known imprinted genes are readily detected demonstrating proof of concept of this approach (2) a number of novel imprinted genes have been identified (3) two novel imprinted gene clusters have been detected. These regions contain a classically imprinted fingerprint with alternative transcripts, CpG islands and direct repeats. Detailed sequence and epigenetic analyses have been useful in defining hallmark features of imprinted genes. We have used these regions as a model for larger scale analyses. Some of our imprinting microarray data has been entered into a database and used as an indicator of differential expression across imprinted regions. The resulting database and its graphical representation as a series of maps compares our microarray data scores that detect differentially expressed genes with non-protein coding transcripts, antisense and alternatively spliced transcripts, GC content and repetitive elements across specific regions of chromosomes 7, 11 & 18. This database compares imprinted versus non-imprinted regions for identification of imprinting features and their correlation to differential gene expression.

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