title: Exact break point of a 50 kb deletion 8 kb centromeric of the HLA-A locus with HLA-A*24:02: the same deletion observed in other A*24 alleles and A*23:01 allele.
abstract: In a structural aberration analysis of patients with arthritis mutilans, a 50 kb deletion near the HLA-A locus with HLA-A*24:02 allele was detected. It was previously reported that HLA-A*24:02 haplotype harbored a large-scale deletion telomeric of the HLA-A gene in healthy individuals. In order to confirm that the deletion are the same in patients with arthritis mutilans and in healthy individuals, and to identify the break point of this deletion, the boundary sequences across the deletion in A*24:02 was amplified by polymerase chain reaction (PCR) as a 3.7 kb genomic fragment and subjected to nucleotide sequence determination. A comparison of these genomic sequences with those of the non-A*24:02 haplotype revealed that the deleted genomic region spanning 50 kb was flanked by 3.7 kb repetitive element-rich segments homologous to each other on both sides in non-A*24. The nucleotide sequences of the PCR products were identical in patients with arthritis mutilans and in healthy individuals, revealing that the deletion linked to A*24:02 is irrelevant to the onset of arthritis mutilans. The deletion was detected in all other A*24 alleles so far examined but not in other HLA-A alleles, except A*23:01. This finding, along with the phylogenic tree of HLA-A alleles and the presence of the 3.7 kb highly homologous segments at the boundary of the deleted genomic region in A*03 and A*32, may suggest that this HLA-A*24:02-linked deletion was generated by homologous recombination within two 3.7 kb homologous segments situated 50 kb apart in the ancestral A*24 haplotype after divergence from the A*03 and A*32 haplotypes.
authors.affiliation: Department of Molecular Life Sciences, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Shimokasuya, Isehara, Kanagawa, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Mitsunaga
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okudaira
authors.forename: Nanae
authors.initials: N
authors.lastname: Kunii
authors.forename: Tailin
authors.initials: T
authors.lastname: Cui
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hosomichi
authors.forename: Akira
authors.initials: A
authors.lastname: Oka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Homma
authors.forename: Shinji
authors.initials: S
authors.lastname: Sato
authors.forename: Ituro
authors.initials: I
authors.lastname: Inoue
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoko
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D002503:Centromere / Q000235:genetics* / Q000276:immunology; D002872:Chromosome Deletion; D002908:Chronic Disease; D056426:Genetic Loci; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology; D059871:HLA-A24 Antigen; D006801:Humans; D010802:Phylogeny
chemical_list: D015234:HLA-A Antigens; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen