Evidence of high genetic variation among linguistically diverse populations on a micro-geographic scale: a case study of the Italian Alps.

Although essential for the fine-scale reconstruction of genetic structure, only a few micro-geographic studies have been carried out in European populations. This study analyzes mitochondrial variation (651 bp of the hypervariable region plus 17 single-nucleotide polymorphisms) in 393 samples from nine populations from Trentino (Eastern Italian Alps), a small area characterized by a complex geography and high linguistic diversity. A high level of genetic variation, comparable to geographically dispersed European groups, was observed. We found a difference in the intensity of peopling processes between two longitudinal areas, as populations from the west-central part of the region show stronger signatures of expansion, whereas those from the eastern area are closer to the expectations of a stationary demographic state. This may be explained by geomorphological factors and is also supported by archeological data. Finally, our results reveal a striking difference in the way in which the two linguistically isolated populations are genetically related to the neighboring groups. The Ladin speakers were found to be genetically close to the Italian-speaking populations and differentiated from the other Dolomitic Ladins, whereas the German-speaking Cimbri behave as an outlier, showing signatures of founder effects and low growth rate.

P525L FUS mutation is consistently associated with a severe form of juvenile amyotrophic lateral sclerosis.

Some FUS mutations have been observed in patients with the juvenile form of Amyotrophic Lateral Sclerosis starting before 25 years. We report an 11-year-old girl affected by sporadic juvenile ALS with a rapid course resulting in tracheostomy after 14 months from the onset. Sequencing FUS gene revealed a de novo P525L mutation. Our findings, together with literature data, indicate that this mutation is consistently associated with a specific phenotype characterized by juvenile onset, severe course and high proportion of de novo mutations in sporadic cases.

Using forensic microsatellites to decipher the genetic structure of linguistic and geographic isolates: A survey in the eastern Italian Alps.

The study of geographically and/or linguistically isolated populations could represent a potential area of interaction between population and forensic genetics. These investigations may be useful to evaluate the suitability of loci which have been selected using forensic criteria for bio-anthropological studies. At the same time, they give us an opportunity to evaluate the efficiency of forensic tools for parentage testing in groups with peculiar allele frequency profiles. Within the frame of a long-term project concerning Italian linguistic isolates, we studied 15 microsatellite loci (Identifiler kit) comprising the CODIS panel in 11 populations from the north-eastern Italian Alps (Veneto, Trentino and Friuli Venezia Giulia regions). All our analyses of inter-population differentiation highlight the genetic distinctiveness of most Alpine populations comparing them either to each other or with large and non-isolated Italian populations. Interestingly, we brought to light some aspects of population genetic structure which cannot be detected using unilinear polymorphisms. In fact, the analysis of genotypic disequilibrium between loci detected signals of population substructure when all the individuals of Alpine populations are pooled in a single group. Furthermore, despite the relatively low number of loci analyzed, genetic differentiation among Alpine populations was detected at individual level using a Bayesian method to cluster multilocus genotypes. Among the various populations studied, the four linguistic minorities (Fassa Valley, Luserna, Sappada and Sauris) showed the most pronounced diversity and signatures of a peculiar genetic ancestry. Finally, we show that database replacement may affect estimates of probability of paternity even when the local database is replaced by another based on populations which share a common genetic background but which differ in their demographic history. These findings point to the importance of considering the demographic and cultural profile of populations in forensic applications, even in a context of substantial genetic homogeneity such as that of European populations.