A Cluster of Novel Imprinted Transcripts at the Gnas Locus on the Distal Imprinting Region of Mouse Chromosome 2

Chris Williamson
Mammalian Genetics Unit; Medical Research Council-UK

The distal region of mouse Chr 2 is subject to parental imprinting as mice carrying maternal duplication/paternal deficiency for distal Chr 2 and its reciprocal exhibit phenotypic anomalies in utero and at birth. Studies of tertiary trisomics suggest that there are at least two oppositely imprinted genes responsible for these effects. A maternally imprinted gene, Nnat, has been excluded as a candidate as it lies proximal to the minimally defined region between 2H3 and 2H4. Our best candidate for imprinting in Gnas as there is clinical and biochemical evidence suggesting that its human homologue is paternally imprinted. Here we show that an extra large transcript of Gnas is exclusively paternally expressed in 11.5 dpc embryos and newborn head, and this supports our previous observation of paternal expression in the kidney glomerulus. Using methylation sensitive representational difference analysis we have detected another imprinted gene. A cloned difference product showed paternal-specific methylation and matched a novel transcript which lies at the Gnas locus. Two isoforms have been detected one of which is exclusively paternally expressed and the other of which is exclusively maternally expressed. Both of these isoforms show the same parental-specific expression from both the sense and antisense strands. The genomic organization of these transcripts is currently under study.