Glucocerebrosidase pseudogene variation and Gaucher disease: Recognizing pseudogene tracts in GBA alleles

We surveyed the genetic variability of the glucocerebrosidase pseudogene (p sGBA) in a worldwide sample of 100 human chromosomes. psGBA is the non func tional duplicate of the gene responsible for Gaucher disease (GBA), the mos t common lipid storage disorder. The existence of only one psGBA allele des cribed until now, together with the high homology between GBA and psGBA, of ten prevented recognition of the complex alleles formed by the combination of GBA and psGBA, because psGBA variants could be confused with GBA mutatio ns. In order to determine the variability existent in psGBA, the whole psGB A DNA segment was PCR-amplified and sequenced, and the genotype for all sam ples was obtained. The ascertainment of the phase among the heterozygous si tes was possible through cloning and sequencing a single allele. Eighteen v ariable sites were detected along psGBA. Two of the variants already have b een reported as Gaucher-causing mutations when present in GBA alleles. The other variants were unknown. The knowledge of the psGBA variants described in this report will allow identification of psGBA-GBA complex alleles that may aid in understanding the intricate phenotype-genotype relationship in G aucher disease. Hum Mutat 17:191-198, 2001. (C) 2001 Wiley-Liss, Inc.