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A molecular investigation of homozygosity for HLA-A3 [Abstract]

Dorak, M. T., Raha-Chowdhury, R., Worwood, Mark, Mills, Kenneth I. and Burnett, Alan Kenneth 1993. A molecular investigation of homozygosity for HLA-A3 [Abstract]. British Journal of Haematology 84 (Sup.1) , p. 59. 10.1111/j.1365-2141.1993.tb06831.x

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The HLA-A3 homozygous genotype frequency has been determined in healthy individuals using the HLA-A (pHLAZa.l), HLA-H related locus D6S128 (p6.7) and HLA-F (pF5UT) DNA probes and Southern blotting with the c e l l l i n e PIL (HLA-A3B7DR2) as reference. The frequency of the HLA-A3-specific (r.0.97; p=lO-’O) RFLP band was 16.4%. Among 226 unrelated individuals, the homozygous genotype was observed only twice (0.9% vs. expected=2.7%, p=O.lO). The genotypical -A3 homozygosity was noted in chronic myeloid leukaemia (4.0$, n.101; 11.4% in the early-onset group, p=O.OOl) and haemochrornatosis (31%, 11.29, p=lO-l”, RR=50.4) patients. This is the highest relative r i s k for any HLA marker in haemochromatosis. In the D6S128 locus, homozygosity for the HLA-A3 associated band was observed a t the expected rate. Healthy individuals homozygous for -A3 have the 0.7kb HLA-A band, whereas, it lacks in disease-associated homozygous genotype. These results suggested that heterogeneity, detectable by an HLA-A probe, might exist in the HLA-A3 haplotypes. Association of -A3 with two HLA-F band supported t h i s possibility. Homozygosity for the disease-associated subtype is decreased in the healthy population. The examination of bone marrow donor r e g i s t r i e s confirmed this conclusion. In the Anthony Nolan registry (n=63200), hornozygosity for the A3B7DR2 haplotype was significantly decreased (p=lO-”). The same trend was observed in a smaller registry (the South Wales BTS registry, n:6606) in which molecular typing results were available (p=O.O8). In a cohort of 282 DNA-typed unrelated healthy individuals from the West of Scotland, there was no decrease in homozygosity for 87DRZ(15) haplotype (2.1% vs. expected 1.1%). These findings suggest that an HLA-A3 subtype in high linkage disequilibrium with HLA-B7DR2 is responsible for the deleterious effects of the haplotype A3B7DR2. The results have implications in HLA-disease association studies ( i n particular leukaemia, haemochromatosis and multiple sclerosis) and also in unrelated donor selection for BMT.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Additional Information: Supplement s1: Abstracts of papers presented at the Annual Scientific Meeting of the British Society for Haematology, Bournemouth, 20-23 April 1993. Article: P139
Publisher: Wiley-Blackwell
ISSN: 0007-1048
Last Modified: 31 Jan 2020 05:15

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