Inactivation of a functional HA-A gene A 4-kb deletion turns HLA-A*24 into a pseudogene

An unusual haplotype without a detectable human leukocyte antigen (HLA)-A allele by serologic or molecular typing methods segregates in a Caucasian family Microsatellite analysis and fluorescence in situ hybridization implicated that the deletion encompasses a narrow region To identify the deleted region five different fragments in close proximity to HLA-A known to be highly polymorphic were amplified and sequenced The presence of heterozygous sequences in all five fragments of the individuals carrying the haplotype with the HLA-A deletion indicates that the fragments are not Involved in the deletion Therefore the 5 primer from the fragment closest to the centromeric side of HLA-A was combined with the 3 primer closest to the telomeric side encompassing an 11-kb region Sequencing revealed that a deletion of 4089 bp was present located upstream of HLA-A including exons and introns 1-3 of the HLA gene Sequence information of the 3 part of HLA-A downstream the deletion identified that the deleted allele originates from an A*24 allele Although different repeat sequences are present in the region both inside and outside the deletion no evidence points to a retrotransposon mechanism The detected partial deletion of HLA-A turns this functional gene into a pseudogene (C) 2010 American Society for Histocompatibility and Immunogenetics Published by Elsevier Inc All rights reserved