Human GRB10 is imprinted and expressed from the paternal and maternal allele in a highly tissue- and isoform-specific fashion

As part of a systematic screen for novel imprinted genes of human chromosom e 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. I n fetal brains, most variants are transcribed exclusively from the paternal allele. Imprinted expression in this tissue is not accompanied by allele-s pecific methylation of the most 5' CpG island. In skeletal muscle, one GRB1 0 isoform, gamma 1, is expressed from the maternal allele alone, whereas in numerous other fetal tissues, all GRB10 splice variants are transcribed fr om both parental alleles, A remarkable finding is paternal-specific express ion of GRB10 in the human fetal brain, since, in the mouse, this gene is tr anscribed exclusively from the maternal allele, To our knowledge, this is t he first example of a gene that is oppositely imprinted in mouse and human.