The aim of this study was to analyse the genetic structure of the Italian bone marrow donor population on the basis of HLA polymorphisms. Maximum likelihood estimates of gene and haplotype frequencies, goodness of fit to Hardy-Weinberg predictions and heterozygosity were calculated for 18 Italian administrative regions. Moreover, the phenotypic peculiarity of the regional populations was assessed by analysing the number of "typical phenotypes" found in each region. Multivariate analyses carried out on HLA-A and HLA-B gene frequencies gave a genetic pattern of the donor pools that reflects the structure of the Italian population determined in previous population genetic studies. Sardinia shows a very large genetic difference with respect to the other regions; of these, the central-southern regions are well-differentiated from the central-northern. Southern regions present higher genetic heterogeneity and a higher probability of providing donors with phenotypes not already present in the Italian bone marrow registry. The large sample size of the bone marrow donor registry allowed us to estimate gene and haplotype frequencies with greater accuracy than in previous studies. Our results may be of use in determining strategies for donor recruitment and selecting unrelated donors for patients requiring bone marrow grafting, as well as for anthropological, epidemiological and population genetics studies.
Data on microgeographic population structure on four neighbouring villages of Sardinia island (Italy) are presented and discussed. Two villages are located in the lowlands where malaria from Plasmodium falciparum was endemic until the eradication of paludism. The other two villages are located in the highlands and they were malaria-free because of the altitude. Census data, inbreeding, migration matrices and surname distributions have been collected. The genetic differentiation of the four villages, tested for 31 genetic polymorphisms (106 alleles), is only in part compatible with migration rates inferred from demographic data. The possible adaptive nature of some genetic markers with respect to malarial resistance is discussed. Ambiguous results from population genetics quantitative methods do not support definite answers.
SUMMARY The association of HLA-A,B,C, DR polymorphisms and of Bf and GLO with coeliac disease was analysed in 100 Italian children. Primary involvement of HLA-DR3 and DR7 is apparent, while specificities of nearby loci are probably associated secondarily, because of linkage disequilibrium. Direct assessment of D/DR genotype through family studies and mixed lymphocyte cultures led to the recognition of two high risk genotypes DR3/3 and DR3/7, and of two lower risk genotypes DR3/X and DR7/X. The different weight of the HLA-dependent genetic factors is to some extent correlated with the clinical and immunological parameters, suggesting that the low-risk genotypes induce a milder expression of coeliac disease. Furthermore, other genetic factors, such as sex, appear to contribute to the penetrance of the disease, especially in the case of DR3/X and DR7/X. Both genetic and environmental factors contribute to the onset and to clinical progression of coeliac disease. The role of genetic factors has long been substantiated by a high concordance rate in monozygotic twins, and an increased incidence of overt malabsorption or of asymptomatic histological lesions in first-degree relatives.' 2 More recently, the association between markers of the HLA system and coeliac disease has provided new evidence of the importance of genetic factors in this disease. 8 Different genetic models have been put forward, which propose dominant or recessive expression of HLA-linked gene(s), or in addition assume the involvement of non-HLA gene(s).9 I() In susceptible individuals, exposure to dietary gluten, or to purified gliadin fractions under experimental conditions, is the leading known environmental factor. Clinical and/or histological improvement on a gluten-free diet and relapse after gluten challenge have thus been established as fixed diagnostic criteria.11 Nevertheless, the protean nature of the clinical picture is adequately shown by the significant proportion of atypical cases.'2 As part of an ongoing study, the present report (1) provides further evidence of the association of
Chronic glomerulonephritis was diagnosed in 23 patients born in a small valley in Northern Italy and in five additional patients with one parent or a more remote ancestor born in the same area, all belonging to three potentially related families. Eighteen patients had biopsy-proven glomerulonephritis: 11 IgA nephropathy, 3 IgM nephropathy, 2 membranoproliferative type I, and 2 mesangial proliferative glomerulonephritis with isolated C3 deposits. Ten had clinical glomerulonephritis. A community screening programme discovered six additional related patients. Two underwent renal biopsy (1 IgA nephropathy; 1 focal glomerulosclerosis); four were diagnosed as having clinical glomerulonephritis. Genealogical investigation identified five deceased family members with diagnoses of chronic nephritis recorded on their death certificates. No environmental nephrotoxic factors were identified. Restriction fragment length polymorphism (RFLP) analysis of HLA-DR beta, HLA-DQ alpha and beta genes, and complement typing for C4A, C4B, and Bf polymorphisms were carried out for 29 patients, 168 healthy relatives, and 24 local controls. The frequency of HLA-Dw8.1 specificity, related to DR beta 8, DQ beta 3b, and DQ alpha 1a RFLPs, was significantly increased more in the affected and unaffected pedigree members than in Italian controls.
Two B-lymphocyte-specific human alloantisera were studied, PA59 and 51.23. They identify two new HLA-DR alleles, which are both subtypic to HLA-DRw2. Moreover, they are closely correlated with two HLA-D products, Dw2 and tb24 (tb24 is a new specificity described by our group). Thus, DRw2 can be "split" into two subtypic specificities that have been named TO60 and TO61, which appear more strongly correlated with HLA-D antigens. Absorption studies demonstrated cytotoxicity-negative, absorption-positive (CYNAP) reactions, and cross-reactive groups of antibodies.
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