title: Inactivation of a functional HLA-A gene: a 4-kb deletion turns HLA-A*24 into a pseudogene.
abstract: 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.
authors.affiliation: Transplantation Immunology, Tissue Typing Laboratory, Maastricht University, Medical Centre, Maastricht, the Netherlands. c.voorter@mumc.nl
authors.forename: Christina E M
authors.initials: CE
authors.lastname: Voorter
authors.forename: Nina
authors.initials: N
authors.lastname: Lauterbach
authors.forename: Marcel G J
authors.initials: MG
authors.lastname: Tilanus
mesh_terms: D000328:Adult; D002648:Child; D005091:Exons; D005190:Family; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics*; D059871:HLA-A24 Antigen; D015395:Histocompatibility Antigens Class I; D006650:Histocompatibility Testing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D011544:Pseudogenes / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D044465:White People / Q000235:genetics
chemical_list: D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D015395:Histocompatibility Antigens Class I