Characterization of a partial pseudogene homologous to the Hermansky-Pudlak syndrome gene HPS-1; relevance for mutation detection.

Abstract

The HPS-1 gene is the first gene found to be responsible for the autosomal recessive disorder Hermansky-Pudlak syndrome (HPS). HPS is characterized by oculocutaneous albinism, a platelet storage pool deficiency, and ceroid lipofuscinosis. The HPS-1 gene has been mapped to chromosome 10q23.1-23.3 and encodes a 79-kDa protein of unknown function with no homology to any known protein. A sequence database search has revealed that a portion of clone HS 1119A7 shows high sequence similarity to HPS-1 cDNA. By performing sequence alignments and PCR amplification of cDNA from several human tissues, we have shown that part of this clone consists of an unprocessed partial HPS-1 pseudogene located on chromosome 22q12.2-12.3. The pseudogene contains several intact HPS-1 exons and shows 95% sequence homology to the HPS-1 cDNA. Exon 6 of the pseudogene has 100% sequence homology to exon 6 of HPS-1 itself. In the pseudogene, this exon is surrounded by portions of both its normal flanking introns. These data provide the first characterization of an HPS-1 pseudogene, called HPS1-psi1. During amplification of exon 6 of the HPS-1 gDNA for mutation identification, the pseudogene might also be amplified, leading to a false positive for mutation. In addition, amplification of specific parts of the HPS-1 cDNA (e.g., exons 2-5) for mutation detection might lead to false positives for mutations, if the cDNA is contaminated with gDNA. This calls for caution when employing these screening approaches.

• Authors: M Huizing, Y Anikster, W A Gahl
• Journal: Human genetics (Hum Genet) Vol. 106 Issue 3 Pg. 370-3 (Mar 2000) ISSN: 0340-6717 [Print] Germany
• PMID: 10798370 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HPS1 protein, human
• Membrane Proteins

Topics

• Albinism, Oculocutaneous (genetics)
• Chromosomes, Human, Pair 10
• Chromosomes, Human, Pair 22
• Databases, Factual
• Exons
• Genetic Testing
• Humans
• Membrane Proteins (genetics)
• Molecular Sequence Data
• Mutation
• Polymerase Chain Reaction
• Pseudogenes (genetics)
• Sequence Homology, Nucleic Acid