Complete Genomic Sequence of the Human PK-L/R-Gene Includes Four Intragenic Polymorphisms Defining Different Haplotype Backgrounds of Normal and Mutant PK-Genes

Abstract

The human pyruvate kinase L/R-gene has been completely sequenced in unrelated normal individuals and in pyruvate kinase-deficient patients by a PCR-based direct genomic sequencing approach and analyzed for polymorphisms. The total length of the gene is 8409 nucleotides. Four polymorphic sites have been detected: C/A1705 and C/T1992 in exon12, 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 found in the variation (ATT)_11-17. Haplotype analysis using these four markers has been applied to trace the generic background in PR-deficiencies. The results support the idea of a single origin of most of the individual PK-mutations.

Key Words:

• Complete sequence
• haplotypes
• human PK-L/R gene
• polymorphic markers