GRB10 (MEG1)






GRB10 (Growth factor receptor-bound protein 10, MEG1).
Blagitko N et al, 2000 reported paternal-specific expression of the beta, gamma1, gamma5, gamma6, epsilon and delta isoforms of GRB10 in fetal brain but maternal-specific expression of the gamma1 isoform in fetal muscle (gamma2 was biallelic in muscle).
Hitchins MP et al, 2001 observed preferential paternal expression of GRB10 specifically in the developing central nervous system including brain and spinal cord, with biallelic expression in peripheral tissues. Although they claimed paternal expression of the beta and delta isoforms in brain, it now seems likely that the 3'UTR based assay for the delta isoform was likely to detect all other isoforms.
McCann JA et al, 2001 showed preferential paternal expression of the gamma 1 isoform in the brain, but biallelic expression of gamma 1 in all other tissues. In contrast, the gamma 2 isoform was predominantly maternally expressed in muscle, but biallelically expressed in all other tissues. Although GRB10 is a candidate for Silver-Russell syndrome, absence of imprinting in growth plate cartilage was presented as evidence against its involvement in SRS.
Yoshihashi H et al 2000 reported that the GRB10 gene is monoallelically expressed in human fetal brain tissues and is transcribed from the maternally derived allele in somatic-cell hybrids.
A maternally methylated DMR has been well documented (chr7:50817247-50818365 NCBI build 36.1) (Arnaud P et al, 2003; Hikichi T et al, 2003).
Disruption of the maternal allele of Grb10 resulted in overgrowth of both the embryo and placenta such that mutant mice were approximately 30% larger than normal (Charalambous M et al, 2003).
Morcos L et al, (2011) found no evidence of allelic expression bias in lymphoblast cell lines.
In their review, Eggermann T et al (2019) conclude that disturbances of the maternally inherited GRB10 copy affect prenatal growth: Duplications or UPD of the maternal allele are associated with prenatal growth retardation, whereas the lack of the maternal copy results in prenatal overgrowth (i.e. in case of upd (7) pat).


Imprinted genes



Last Modified 6/9/2019


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