Because defects in the phenylalanine hydroxylase gene (PAH) cause phenylketonuria (PKU), PAH was studied for normal polymorphisms and linkage disequilibrium soon after the gene was cloned. Studies in the 1980s concentrated on European populations in which PKU was common and showed that haplotype-frequency variation exists between some regions of the world. In European populations, linkage disequilibrium generally was found not to exist between
RFLPs at opposite ends of the gene but was found to exist among the RFLPs clustered at each end. We have now undertaken the first global survey of normal variation and disequilibrium across the PAH gene.

Haplotypes and linkage disequilibrium at the phenylalanine hydroxylase locus, PAH, in a global representation of populations