Genomic studies of the spleen protein tyrosine kinase locus reveal a complex promoter structure and several genetic variants.

Here we show that the gene of the cytoplasmic tyrosine kinase SYK spans a region of 90 kb with 13 coding exons, an alternative exon 14 and at least two 5' untranslated regions exons 1a and 1b. 5' RACE (Rapid amplification of cDNA ends) of human Syk cDNAs demonstrated a complex promoter usage and splicing pattern. We identified three common single nucleotide polymorphisms in the exon la promoter region of the Syk gene as well as a variant Syk cDNA haplotype. This haplotype was characterized by a constellation of 5 silent mutations in the Syk cDNA: 1065(C-T), 1302(G-C), 1338(G-A), 1521 (C-T) and 1545(T-C). A hypervariable CATATA(n) repeat polymorphism was also localized to the intron between exons 11 and 12. These novel insights into the genomic organization, promoter structure and genetic variability of Syk will serve as a foundation for detailed molecular epidemiological investigation of its potential role in human cancer biology.