Organization, expression and polymorphism of the human persyn gene

Persyn is a recently identified member of the synuclein family with adistinct pattern of expression during pre- and postnatal development of themouse peripheral and central nervous systems. As with other synucleins,persyn is believed to be involved in the pathogenesis of humanneurodegenerative diseases. However, in contrast to other synucleins, highlevels of persyn mRNA expression were also found in advanced breastcarcinomas, suggesting an involvement of the encoded protein in breasttumour progression. Here we have used an antibody specific to human persynto demonstrate that the level of this protein is increased in ageingcerebral cortex and in breast tumours. We cloned, characterized andsequenced the human persyn genomic locus and localized it to the long armof chromosome 10 in the q23.2-q23.3 region. Sequence information was usedto search for specific mutations in the protein coding regions of persynmRNA and the persyn gene in breast tumours and tumour cell lines. Notumour-specific mutations were found, but two linked polymorphisms in thecoding region were detected, both in mRNA and exons III and IV of the gene.These results suggest that development of breast tumours correlates withoverexpression of the wild-type persyn protein. Detailed characterizationof the human persyn locus is important for further studies of theinvolvement of persyn in neurodegeneration and malignancy.