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Multivarate techniques can be used to condense the information for a large number of loci and alleles into one or a few synthetic variables. The geographic distribution of synthetic variables can be plotted by the same technique used in mapping the gene frequency of a single allele. Synthetic maps were constructed for Europe and the Near East, with the use of principal components to condense the information of 38 independent alleles from ten loci. The first principal component summarizes close to 30% of the total information and shows gradients. Maps thus constructed show clines in remarkable agreement with those expected on the basis of the spread of early farming in Europe, thus supporting the hypothesis that this spread was a demic spread rather than a cultural diffusion of farming technology.

A well defined Italian sample from Trino Vercellese (Northern Italy) is analysed for 75 nuclear DNA RFLPs. It represents the only European sample [Matullo et al 1994] which is unmixed in a comparative study of eight populations from four continents [Bowcock et al 1991a; Lin et al 1994]. Genetic substructure of this sample has been investigated by allele sharing distances and no bias or higher homogeneity is shown. Genetic variability between populations was measured by the FST statistics (average FST was 0.138 +/- 0.086). Average heterozygosity for eight populations was 0.312 +/- 0.069. Genetic distances were evaluated between pairs of populations. Phylogenetic trees were reconstructed and principal component analysis performed. Particular attention has been given to the genetic relationship between our sample and the mixed-Caucasoid sample: 14 out of 75 markers show statistically significant frequency differences (P0.05), 5 of which are significant at a probability level1%: GH/Bg1II (Lower system), D7S1/HindIII, D17S71/MspI, EPB3/PstI, HLA-DQA. Hypotheses on admixed origin of Europeans has been discussed.

Wilson disease (WND) is an autosomal recessive disorder that is due to an inability of the liver to eliminate copper. Copper buildup in the liver, brain, kidney, and other tissues can result in liver cirrhosis, neurologic and psychiatric defects, and other problems. We have localized the disease-containing region to between D13S31 and D13S59, with > 70 multiply affected families, and have constructed a YAC contig of > 4.5 Mb that spans these loci and orders nine highly polymorphic microsatellites. Here we present an analysis of disequilibrium with markers in this interval and provide evidence for strong allelic associations between AFM084xc5 alleles and WND alleles in European, Middle Eastern, and East Asian populations. Significant but weaker allelic associations were also observed between WND alleles and alleles at D13S137 and D13S169. The strength of the association between AFM084xc5 and WND in all non-Sardinian populations combined (linkage-disequilibrium coefficient [phi] = .61) suggests that the number of mutations accounting for WND is less than expected on the basis of the variety of clinical symptoms that are observed.

The immunoglobulin kappa light chain (IgK) locus may play a significant role in the pathology of both infectious and autoimmune diseases. Most of the work on IgK genetics has been conducted using immunological techniques for allelic typing and sequence analysis. This is restricted by availability of reagents and can be both expensive and time-consuming. PCR primers were designed to amplify the kappa constant gene (Ck), and four allele-specific oligonucleotides (ASOs) were used to distinguish the alleles in the amplified PCR products. Direct sequencing of PCR products was performed to confirm that the primers specifically amplified the Ck region and the ASOs differentiated the Km alleles. Sequencing of an average of 209 nucleotides of DNA from 50 individuals revealed no variation except at codon 191, which is known to be involved in a frequent polymorphism. An analysis of 347 different individual DNAs from 10 human populations was conducted to determine Km allelic frequencies within these populations and to apply this type of data collection to population studies.

We analysed a sample of 55 unrelated individuals from Trino Vercellese, a village in northern Italy. It represents the only European sample which is unmixed in a comparative study of eight populations from four continents [Bowcock et al 1991a; Lin et al 1994]. RFLP analysis was performed on 32 DNA markers, for a total of 37 independent alleles. Genetic variability between populations was measured by the FST statistics (average FST is 0.138). Average heterozygosity was calculated for each marker and for each population. Genetic distances were evaluated between pairs of populations. Phylogenetic trees were reconstructed and principal component analysis performed.

The demographic history of India was examined by comparing mtDNA sequences obtained from members of three culturally divergent Indian subpopulations (endogamous caste groups). While an inferred tree revealed some clustering according to caste affiliation, there was no clear separation into three genetically distinct groups along caste lines. Comparison of pairwise nucleotide difference distributions, however, did indicate a difference in growth patterns between two of the castes. The Brahmin population appears to have undergone either a rapid expansion or steady growth. The low-ranking Mukri caste, however, may have either maintained a roughly constant population size or undergone multiple bottlenecks during that period. Comparison of the Indian sequences to those obtained from other populations, using a tree, revealed that the Indian sequences, along with all other non-African samples, form a starlike cluster. This cluster may represent a major expansion, possibly originating in southern Asia, taking place at some point after modern humans initially left Africa.