Human Molecular Genetics, 2000, Vol. 9, No. 11 1587-1595
© 2000 Oxford University Press
Human GRB10 is imprinted and expressed from the paternal and maternal allele in a highly tissue- and isoform-specific fashion
1Max-Planck-Institute for Molecular Genetics, Ihnestrasse 73, D-14195 Berlin (Dahlem), Germany, 2Department of Human Genetics, RWTH Aachen, Germany, 3Universitäts-Kinderklinik Tübingen, Germany, 4Departments of Molecular and Human Genetics, and Pediatrics, Baylor College of Medicine, Houston, TX, USA and 5Department of Human Genetics, University Hospital Nijmegen, The Netherlands
As part of a systematic screen for novel imprinted genes of human chromosome 7 we have investigated GRB10, which belongs to a small family of adapter proteins, known to interact with a number of receptor tyrosine kinases and signalling molecules. Upon allele-specific transcription analysis involving multiple distinct splice variants in various fetal tissues, we found that human GRB10 is imprinted in a highly isoform- and tissue-specific manner. In fetal brains, most variants are transcribed exclusively from the paternal allele. Imprinted expression in this tissue is not accompanied by allele-specific methylation of the most 5' CpG island. In skeletal muscle, one GRB10 isoform, 
1, is expressed from the maternal allele alone, whereas in numerous other fetal tissues, all GRB10 splice variants are transcribed from both parental alleles. A remarkable finding is paternal-specific expression of GRB10 in the human fetal brain, since, in the mouse, this gene is transcribed exclusively from the maternal allele. To our knowledge, this is the first example of a gene that is oppositely imprinted in mouse and human.
+ These authors contributed equally to this work
§ To whom correspondence should be addressed. Tel: +49 30 8413 1293; Fax: +49 30 8413 1383; Email: kalscheuer@molgen.mpg.de
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