Susceptibility to complex diseases in Sardinian population explained by Runs of Homozygosity and genomic regions under positive selection

Aim: 1)Confirm and detail the homogeneity of the Sardinian population at interregional level based on the analysis "genome-wide" through the use of "Runs of Homozygosity" (RoHS);2) infer the genetic history of the Sardinian population by estimating the level of genetic background of the common ancestry within the island and compare it to the Italian peninsula; 3)Identify indicators of positive selection. Methods: About single nucleotide polymorphisms (SNPs) genotyped in 1077 Sardinian individuals were used to investigate the genetic population structure, as well as to estimate RoH and Extended Haplotype Homozygosity regions. We used four different methods: fixation index, inflaction factor, multi-dimensional scaling and ancestry estimation. we were able to highlight, as expected from a genetic isolate, the high internal homogeneity of the island. Comparing Sardinia to mainland Italy through several classes of RoH. Conclusion: We confirmed the high genetic homogeneity of Sardinia and we have shown that the genome of the Sardinians has mean inbreeding coefficients which are higher than those of mainland Italians. Furthermore, the Sardinian’s genome still preserves traces of the elaborate demographic history of the island. In addition, we observed that some genomic regions showing signs of positive selection

L’universale incompleto. Questione liberale ed emancipazione = L’universel incomplet : la question libérale et l’émancipation = The incomplete universal: the liberal question and emancipation

In defining his particular conception of the philosophy of praxis as absolute historicism, Gramsci intertwines certain fundamental themes of political philosophy, primarily the relationship between civil and political society in the dialectic of freedoms. He conceives the process of human emancipation as a continuation/reversal of the universal values immanent to bourgeois revolutions. According to Gramsci, the transition from liberalism to socialism was historically situated in this passage from incomplete universality to complete emancipation,. The young Sardinian intellectual’s anti-protectionist polemics and his particular way of viewing the Southern Question—understood as a paradigmatic linkage of the organic contradictions inherentin the formation of Italy as a nation—fit into this vision. He did not become aware of the parasitic and regressive function of protectionism in Einaudian academic circles in Turin, but in Sardinia, where this phenomenon occurred at the end of a long historical process of passive modernisation which, in many ways, anticipated the post-unification Southern Question

La dialettica tra 'vecchio e nuovo'. Gramsci e la marcia dell’universalità nelle note di Domenico Losurdo

Losurdo inscrive la transizione di Gramsci dal liberalismo al comunismo critico nella lunga marcia dell’universalità, in quella interminabile dialettica tra vecchio e nuovo all’interno della quale si si-tuano contraddizioni e salti qualitativi immanenti al divenire storico. Le prospettive di trasformazio-ne radicale della società, attorno all’idea di integrale emancipazione umana, sarebbero uno sviluppo del principio di universale dignità dell’uomo (in contrapposizione al particolarismo giuridico aristo-cratico-feudale) al centro dei rivolgimenti politici di fine Settecento e inizio Ottocento. Gramsci non intende fare del socialismo un becchino della società borghese, ma il suo erede. In tal senso si pose in termini dialettici, concependo l’avvento del nuovo ordine come superamento del vecchio, non la sua semplice negazione. Così, anche in una fase storica segnata dalla grave crisi del liberalismo italiano, disposto a mettere da parte le proprie istituzioni e i suoi valori ideali pur di impedire il cambiamento dell’ordine sociale, Gramsci concepisce il socialismo all’interno di un processo ascendente e progressi-vo apertosi con la distruzione del vecchio ordine feudale, trovando in Hegel il filosofo che con maggior sistematicità ha saputo concettualizzare il trapasso dal vecchio Stato patrimoniale per caste chiuse al moderno Stato etico

Mendelian breeding units <i>versus</i> standard sampling strategies: mitochondrial DNA variation in southwest Sardinia

We report a sampling strategy based on Mendelian Breeding Units (MBUs), representing an interbreeding group of individuals sharing a common gene pool. The identification of MBUs is crucial for case-control experimental design in association studies. The aim of this work was to evaluate the possible existence of bias in terms of genetic variability and haplogroup frequencies in the MBU sample, due to severe sample selection. In order to reach this goal, the MBU sampling strategy was compared to a standard selection of individuals according to their surname and place of birth. We analysed mitochondrial DNA variation (first hypervariable segment and coding region) in unrelated healthy subjects from two different areas of Sardinia: the area around the town of Cabras and the western Campidano area. No statistically significant differences were observed when the two sampling methods were compared, indicating that the stringent sample selection needed to establish a MBU does not alter original genetic variability and haplogroup distribution. Therefore, the MBU sampling strategy can be considered a useful tool in association studies of complex traits

Mendelian breeding units versus standard sampling strategies: Mitochondrial DNA variation in southwest Sardinia

We report a sampling strategy based on Mendelian Breeding Units (MBUs), representing an interbreeding group of individuals sharing a common gene pool. The identification of MBUs is crucial for case-control experimental design in association studies. The aim of this work was to evaluate the possible existence of bias in terms of genetic variability and haplogroup frequencies in the MBU sample, due to severe sample selection. In order to reach this goal, the MBU sampling strategy was compared to a standard selection of individuals according to their surname and place of birth. We analysed mitochondrial DNA variation (first hypervariable segment and coding region) in unrelated healthy subjects from two different areas of Sardinia: the area around the town of Cabras and the western Campidano area. No statistically significant differences were observed when the two sampling methods were compared, indicating that the stringent sample selection needed to establish a MBU does not alter original genetic variability and haplogroup distribution. Therefore, the MBU sampling strategy can be considered a useful tool in association studies of complex traits

Sardinians genetic background explained by runs of homozygosity and genomic regions under positive selection

The peculiar position of Sardinia in the Mediterranean sea has rendered its population an interesting biogeographical isolate. The aim of this study was to investigate the genetic population structure, as well as to estimate Runs of Homozygosity and regions under positive selection, using about 1.2 million single nucleotide polymorphisms genotyped in 1077 Sardinian individuals. Using four different methods - fixation index, inflation factor, principal component analysis and ancestry estimation - we were able to highlight, as expected for a genetic isolate, the high internal homogeneity of the island. Sardinians showed a higher percentage of genome covered by RoHs&gt;0.5 Mb (FRoH%0.5) when compared to peninsular Italians, with the only exception of the area surrounding Alghero. We furthermore identified 9 genomic regions showing signs of positive selection and, we re-captured many previously inferred signals. Other regions harbor novel candidate genes for positive selection, like TMEM252, or regions containing long non coding RNA. With the present study we confirmed the high genetic homogeneity of Sardinia that may be explained by the shared ancestry combined with the action of evolutionary forces