Inferring Signatures of Positive Selection in Whole-Genome Sequencing Data: An Overview of Haplotype-Based Methods

Signatures of positive selection in the genome are a characteristic mark of adaptation that can reveal an ongoing, recent, or ancient response to environmental change throughout the evolution of a population. New sources of food, climate conditions, and exposure to pathogens are only some of the possible sources of selective pressure, and the rise of advantageous genetic variants is a crucial determinant of survival and reproduction. In this context, the ability to detect these signatures of selection may pinpoint genetic variants that are responsible for a significant change in gene regulation, gene expression, or protein synthesis, structure, and function. This review focuses on statistical methods that take advantage of linkage disequilibrium and haplotype determination to reveal signatures of positive selection in whole-genome sequencing data, showing that they emerge from different descriptions of the same underlying event. Moreover, considerations are provided around the application of these statistics to different species, their suitability for ancient DNA, and the usefulness of discovering variants under selection for biomedicine and public health in an evolutionary medicine framework

Human pangenomics: promises and challenges of a distributed genomic reference

A pangenome is a collection of the common and unique genomes that are present in a given species. It combines the genetic information of all the genomes sampled, resulting in a large and diverse range of genetic material. Pangenomic analysis offers several advantages compared to traditional genomic research. For example, a pangenome is not bound by the physical constraints of a single genome, so it can capture more genetic variability. Thanks to the introduction of the concept of pangenome, it is possible to use exceedingly detailed sequence data to study the evolutionary history of two different species, or how populations within a species differ genetically. In the wake of the Human Pangenome Project, this review aims at discussing the advantages of the pangenome around human genetic variation, which are then framed around how pangenomic data can inform population genetics, phylogenetics, and public health policy by providing insights into the genetic basis of diseases or determining personalized treatments, targeting the specific genetic profile of an individual. Moreover, technical limitations, ethical concerns, and legal considerations are discussed

Update on the safety and efficacy of teriparatide in the treatment of osteoporosis

Following the completion of the Fracture Prevention Trial, teriparatide was approved by the United States Food and Drug Administration and the European Medicine Agency as the first therapeutic anabolic agent for the treatment of postmenopausal women with severe osteoporosis. It subsequently received additional approval for the treatment of osteoporosis in men, and for the treatment of osteoporosis associated with glucocorticoid therapy in men and women at risk of fracture. In this review, we summarize the most important data concerning PTH 1-34 therapy before 2016 in the treatment of osteoporosis, and report some outstanding results published in the last 2 years. New data on safety will also discussed, together with the state of art of nonclassical utilization. Finally, in view of the recent approval of biosimilars, possible future landscapes are discussed

Effects of miRNA-15 and miRNA-16 expression replacement in chronic lymphocytic leukemia : implication for therapy

This work was supported by: Associazione Italiana Ricerca sul Cancro (AIRC) Grant 5 x mille n.9980, (to M.F., F.M. A. N., P.T. and M.N.) ; AIRC I.G. n. 14326 (to M.F.), n.10136 and 16722 (A.N.), n.15426 (to F.F.). AIRC and Fondazione CaRiCal co-financed Multi Unit Regional Grant 2014 n.16695 (to F.M.). Italian Ministry of Health 5x1000 funds (to S.Z. and F.F). A.G R. was supported by Associazione Italiana contro le Leucemie-Linfomi-Mielomi (AIL) Cosenza - Fondazione Amelia Scorza (FAS). S.M. C.M., M.C., L.E., S.B. were supported by AIRC.Peer reviewedPostprin

Genetic history of Calabrian Greeks reveals ancient events and long term isolation in the Aspromonte area of Southern Italy

Calabrian Greeks are an enigmatic population that have preserved and evolved a unique variety of language, Greco, survived in the isolated Aspromonte mountain area of Southern Italy. To understand their genetic ancestry and explore possible effects of geographic and cultural isolation, we genome-wide genotyped a large set of South Italian samples including both communities that still speak Greco nowadays and those that lost the use of this language earlier in time. Comparisons with modern and ancient populations highlighted ancient, long-lasting genetic links with Eastern Mediterranean and Caucasian/Near-Eastern groups as ancestral sources of Southern Italians. Our results suggest that the Aspromonte communities might be interpreted as genetically drifted remnants that departed from such ancient genetic background as a consequence of long-term isolation. Specific patterns of population structuring and higher levels of genetic drift were indeed observed in these populations, reflecting geographic isolation amplified by cultural differences in the groups that still conserve the Greco language. Isolation and drift also affected the current genetic differentiation at specific gene pathways, prompting for future genome-wide association studies aimed at exploring trait-related loci that have drifted up in frequency in these isolated groups

Pliocene colonization of the Mediterranean by Great White Shark inferred from fossil records, historical jaws, phylogeographic and divergence time analyses

Aim: Determine the evolutionary origin of the heretofore poorly characterized contemporary Great White Shark (GWS; Carcharodon carcharias) of the Mediterranean Sea, using phylogenetic and dispersal vicariance analyses to trace back its global palaeo-migration pattern. Location: Mediterranean Sea. Taxon: Carcharodon carcharias. Methods: We have built the largest mitochondrial DNA control region (CR) sequence dataset for the Mediterranean GWS from referenced historical jaws spanning the 19th and 20th centuries. Mediterranean and global GWS CR sequences were analysed for genetic diversity, phylogenetic relationships and divergence time. A Bayes factor approach was used to assess two scenarios of GWS lineage divergence and emergence of the Mediterranean GWS line using fossil records and palaeo-geographical events for calibration of the molecular clock. Results: The results confirmed a closer evolutionary relationship between Mediterranean GWS and populations from Australia–New Zealand and the North-eastern Pacific coast rather than populations from South African and North-western Atlantic. The Mediterranean GWS lineage showed the lowest genetic diversity at the global level, indicating its recent evolutionary origin. An evaluation of various divergence scenarios determined the Mediterranean GWS lineage most likely appeared some 3.23 million years ago by way dispersal/vicariance from Australian/Pacific palaeo-populations. Main conclusion: Based on the fossil records, phylogeographic patterns and divergence time, we revealed that the Mediterranean GWS population originated in the Pliocene following the Messinian Salinity Crisis. Colonization of the Mediterranean by GWS likely occurred via an eastward palaeo-migration of Australian/eastern Pacific elements through the Central American Seaway, before the complete closure of the Isthmus of Panama. This Pliocene origin scenario contrasts with a previously proposed scenario in which Australian GWS colonized the Mediterranean via antipodean northward migration resulting from navigational errors from South Africa during Quaternary climatic oscillations

HGF Mediates the Anti-inflammatory Effects of PRP on Injured Tendons

Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2. © 2013 Zhang et al