We report a large genomic deletion of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, viz., a deletion that is frequently observed in Central and Eastern Europe. The mutation, termed CFTRdele2,3(21 kb), deletes 21,080 bp spanning introns 1-3 of the CFTR gene. Transcript analyses have revealed that this deletion results in the loss of exons 2 and 3 in epithelial CFTR mRNA, thereby producing a premature termination signal within exon 4. In order to develop a simple polymerase chain reaction assay for this allele, we defined the end-points of the deletion at the DNA sequence level. We next screened for this mutation in a representative set of European and European-derived populations. Some 197 CF patients, including seven homozygotes, bearing this mutation have been identified during the course of our study. Clinical evaluation of CFTRdele2,3(21 kb) homozygotes and a comparison of compound heterozygotes for deltaF508/CFTRdele2,3(21 kb) with pairwise-matched deltaF508 homozygotes indicate that this deletion represents a severe mutation associated with pancreatic insufficiency and early age at diagnosis. Current data show that the mutation is particularly common in Czech (6.4% of all CF chromosomes), Russian (5.2%), Belorussian (3.3%), Austrian (2.6%), German (1.5%), Polish (1.5%), Slovenian (1.5%), Ukrainian (1.2%), and Slovak patients (1.1%). It has also been found in Lithuania, Latvia, Macedonia and Greece and has sporadically been observed in Canada, USA, France, Spain, Turkey, and UK, but not in CF patients from Bulgaria, Croatia, Romania or Serbia. Haplotype analysis has identified the same extragenic CF-haplotype XV-2c/KM. 19 "A" and the same infrequent intragenic microsatellite haplotype 16-33-13 (IVS8CA-IVS 17bTA-IVS 17bCA) in all examined CFTRdele2,3(21 kb) chromosomes, suggesting a common origin for this deletion. We conclude that the 21-kb deletion is a frequent and severe CF mutation in populations of Eastern- and Western-Slavic descent.

For many years it has been assumed that the population of Uruguay is almost exclusively European-derived and that the biological contribution of the native population as well as of individuals of African descent is negligible. Several recent studies based on a variety of genetic markers, mostly morphological and serological markers, have produced quite a different picture of the constitution of the Uruguayan population. The Native American contribution varies from 1-20%, while the African contribution ranges from 7-15%, in different regions of the country. In the present study we examine the way the admixture process took place in Uruguay by analyzing the ancestry of maternal lineages in a sample from the northern city of Tacuarembó. To accomplish this goal we typed mitochondrial DNA (mtDNA) markers of Native American, African, and European origin and estimated the proportions of each parental group in the admixed population. We found that 62% of all mtDNA haplogroups were of Native American descent, a surprising figure considering the "European roots" of the country. Consequently, this result assimilates Uruguay to the rest of Latin American populations where sex-biased gene flow between European men and Native American women has been the rule. We further analyzed the distribution of the four major founding mitochondrial lineages in Tacuarembó and compared it to other South American populations. We discuss our findings in the light of historical records and assess the need for additional genetic studies.

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In the present paper we report a technique which permits the simultaneous observation of C-banded material and the active NORs or nucleoli in both mitotic and meiotic chromosomes of mammals and insects. The use of the present technique permits to establish a complete correlation between the C-banded positive regions and the presence of nucleoli associated to them. Some aspects related with this correspondence are discussed.