Microgeographic variation of HLA-A, -B, and -DR haplotype frequencies in Tuscany, Italy: implications for recruitment of bone marrow donors F. Marroni M. Curcio S. Fornaciari S. Lapi M. L. Mariotti F. Scatena S. Presciuttini Authors’ affiliations: F. Marroni 1,2 , M. Curcio 3 , S. Fornaciari 3 , S. Lapi 3 , M. L. Mariotti 3 , F. Scatena 3 , S. Presciuttini 2,4 , 1 Department of Oncology, Transplants and New Technologies in Medicine, Section of Pathology, University of Pisa, Pisa, Italy 2 Center of Statistical Genetics, University of Pisa, Pisa, Italy 3 U.O. Immunoematologia 2 – Azienda Ospedaliera Pisana, Pisa, Italy 4 Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland, USA Correspondence to: Silvano Presciuttini Center of Statistical Genetics, S.S. Abetone e Brennero 2, 56127 Pisa, Italy e-mail: sprex@biomed.unipi.it Abstract: HLA-A/B haplotype frequencies were estimated in a sample of 2355 bone marrow donors born in a subregion of Tuscany (Italy), and the HLA-A, -B, -DR haplotype frequencies were estimated in a subset of 809 individuals. This area was divided in 10 subsamples (two-locus haplotypes), or six subsamples (three-locus haplotypes), all with sample size >50, based on administrative boundaries. A considerable level of heterogeneity of haplotype frequency was present among subsamples; this heterogeneity was associated to a large variation (up to 4-fold) of the number of new donors that must be typed in order to reach 50% chance of finding an HLA-A, -B phenotype of intermediate frequency. Knowledge of the genetic structure of the population at a microgeographic level may be useful in directing the search of specific bone marrow donors. Human leukocyte antigen (HLA) genes, located on the short arm of chromosome 6 (1), are widely recognized as highly informative genetic markers. Because of their high levels of polymorphism, HLA loci have been widely used in human population genetics, to cast light on the genetic structure and differentiation of populations, both at the worldwide level and at a smaller scale (2–5). The most relevant clinical application of HLA typing has been donor selection for bone marrow transplantation. Knowledge of HLA haplotype frequencies and related population genetic parameters is of crucial importance for planning a recruitment strategy for donor registries (5–7). The Italian Bone Marrow Donor Registry (IBMDR) currently con- tains more than 290,000 individuals typed for class I HLA-A and -B loci (8). Previous studies compared haplotype frequencies among regions (9) and among municipalities of the same region (6). In the present work, we investigated the extent of haplotype frequency variation at a small geographic scale and applied the results to the problem of searching specific bone marrow donors. We used data from the Bone Marrow Donor Registry of Pisa (CDPI01), which Key words: bone marrow donors; haplotype frequency; HLA; Tuscany Received 2 March 2004, revised 25 May 2004, accepted for publication 31 May 2004 Copyright ß Blackwell Munksgaard 2004 doi: 10.1111/j.1399-0039.2004.00292.x Tissue Antigens 2004: 64: 478–485 Printed in Denmark. All rights reserved 478