COMPLETE GENOMIC SEQUENCE OF THE HUMAN PK-L R-GENE INCLUDES 4 INTRAGENIC POLYMORPHISMS DEFINING DIFFERENT HAPLOTYPE BACKGROUNDS OF NORMAL AND MUTANT PK-GENES/

The human pyruvate kinase L/R-gene has been completely sequenced in un related normal individuals and in pyruvate kinase-deficient patients b y a PCR-based direct genomic sequencing approach and analyzed for poly morphisms. The total length of the gene is 8409 nucleotides. Four poly morphic sites have been detected: C/A1705 and C/T1992 in exon 12, a T- stretch in intron I occuring in the two polymorphic forms (T)(10) and (T)(19) and an (ATT)(n) microsatellite in intron J which has been foun d in the variation (ATT)(11-17). Haplotype analysis using these four m arkers has been applied to trace the genetic background in PK-deficien cies. The results support the idea of a single origin of most of the i ndividual PK-mutations.