Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.

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We report on a 3-year-old boy with moderate developmental retardation, microcephaly, and malformations of ears, lids, mouth, and thumbs. Cytogenetic analysis demonstrated a direct duplication of chromosome subregion 4(q21.3-->q31.3). Confirmation of this specific rearrangement was performed by fluorescent in situ hybridization (FISH) with a chromosome painting probe and by means of quantitative Southern hybridization with DNA probes localized within the chromosome 4 region presumed to be duplicated.

Our study has shown that in carcinoma cells (ATC, PTC, MTC), IGF-I reveals a stimulatory influence on the expression of its own gene, that effect being most distinctive in ATC cells. These facts indicate an important role of IGF-I in the pathogenesis and invasiveness of the analyzed malignant neoplasms.

Congenital hypothyroidism (CH) occurs approximately with a frequency of 1 in 3000-4000 births, being a disease caused by defects in thyroid hormone synthesis associated either with goiter presence or with agenesis or ectopy of the thyroid gland. A study of some familial cases has allowed identification of mutations in several known genes, including that encode the thyroid-stimulating hormone receptor (TSHR). We report a familial case of CH that transmitted as a recessive trait and caused by a novel homozygous nonsense mutation in TSHR with an initial diagnosis of thyroid agenesis hypoplasia. Genomic DNA was obtained from two siblings and their parents; TSHR was amplified using pairs of overlapping exonic primers; and polymerase chain reaction products were automatically sequenced. The propositus was homozygous (genotype: M/M) for a novel C to G transversion (1431C>G), producing a nonsense mutation, Y444X, in the first intracellular loop of TSHR, rendering a truncated receptor. Thus, the observed unresponsiveness to TSHR may be due to absent insertion of the truncated receptor into the cell membrane (if it gets translated at all) or the truncation may lead to nonsense-mediated mRNA degradation (its unresponsive to TSH). Both parents were heterozygous (wWt/M) and unrelated, as known from family history. The other daughter was homozygous for both wild-type alleles (wWt/wWt).

We have performed cytogenetic and molecular analyses of 45,X mosaics involving structurally abnormal Y chromosomes. Karyotypes were performed by standard cytogenetic methods and, in some cases, by fluorescence in situ hybridization, to distinguish monocentric and dicentric chromosomes. In addition, the deletions of Yq have been mapped using Southern blotting and polymerase chain reaction analysis. This paper provides additional information on the analysis of Y chromosome aberrations, and suggests that the stability of the Y chromosome in these instances is related to the site of the break point on Yq.

Cu/Zn superoxide dismutase (SOD‐1) (E.C.1.15.1.1.) activity was estimated in children with regular trisomy 21‐Down syndrome as well as in cases of translocation and mosaic trisomy 21, as identified by the GTG, CBG and RHG banding techniques. SOD‐1 activity was found to be increased in all examined cases except trisomy 21 mosaicism. These findings provide further proof of the gene dosage theory and additional biochemical evidence for the triplicate existence of the SOD‐1 gene localized on chromosome 21