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Host genomic information, specifically genomic variations, may characterize susceptibility to disease and identify people with a higher risk of harm, leading to better targeting of care and vaccination. Italy was the epicentre for the spread of COVID-19 in Europe, the first country to go into a national lockdown and has one of the highest COVID-19 associated mortality rates. Qatar, on the other hand has a very low mortality rate. In this study, we compared whole-genome sequencing data of 14398 adults and Qatari-national to 925 Italian individuals. We also included in the comparison whole-exome sequence data from 189 Italian laboratory-confirmed COVID-19 cases. We focused our study on a curated list of 3619 candidate genes involved in innate immunity and host-pathogen interaction. Two population-gene metric scores, the Delta Singleton-Cohort variant score (DSC) and Sum Singleton-Cohort variant score (SSC), were applied to estimate the presence of selective constraints in the Qatari population and in the Italian cohorts. Results based on DSC and SSC metrics demonstrated a different selective pressure on three genes (MUC5AC, ABCA7, FLNA) between Qatari and Italian populations. This study highlighted the genetic differences between Qatari and Italian populations and identified a subset of genes involved in innate immunity and host-pathogen interaction.

Whole genome sequencing (WGS) allows the identification of human knockouts (HKOs), individuals in whom loss of function (LoF) variants disrupt both alleles of a given gene. HKOs are a valuable model for understanding the consequences of genes function loss. Naturally occurring biallelic LoF variants tend to be significantly enriched in "genetic isolates," making these populations specifically suited for HKO studies. In this work, a meticulous WGS data analysis combined with an in-depth phenotypic assessment of 947 individuals from three Italian genetic isolates led to the identification of ten biallelic LoF variants in ten OMIM genes associated with known autosomal recessive diseases. Notably, only a minority of the identified HKOs (C7, F12, and GPR68 genes) displayed the expected phenotype. For most of the genes, instead, (ACADSB, FANCL, GRK1, LGI4, MPO, PGAM2, and RP1L1), the carriers showed none or few of the signs and symptoms typically associated with the related diseases. Of particular interest is a case presenting with a FANCL biallelic LoF variant and a positive diepoxybutane test but lacking a full Fanconi anemia phenotypic spectrum. Identifying KO subjects displaying expected phenotypes suggests that the lack of correct genetic diagnoses may lead to inappropriate and delayed treatment. In contrast, the presence of HKOs with phenotypes deviating from the expected patterns underlines how LoF variants may be responsible for broader phenotypic spectra. Overall, these results highlight the importance of in-depth phenotypical characterization to understand the role of LoF variants and the advantage of studying these variants in genetic isolates., (© 2021. The Author(s).)

The assessment of the distribution and composition of microlitter in the sea is a great challenge. Biological indicators can be an irreplaceable tool since they measure microlitter levels in their environments in a way that is virtually impossible to replicate by direct physical measurements. Furthermore, trends can provide policymakers with statistically robust analysis. We looked into the capacity of multiple fish species to describe the distribution and composition of microlitter vertically across different compartments of the water column. A total of 502 individuals from six selected species (Scomber scombrus, Oblada melanura, Spicara smaris, Boops boops, Merluccius merluccius and Mullus barbatus) were collected on the western side of Sardinia island and allocated to three compartments: surface, mid-water and bottom. The species of the surface exhibited a higher frequency of occurrence (41.89%) of microlitter ingestion, compared to those of the mid-water and bottom (19.60%; 22.58%). A significant difference in the average number of ingested microlitter was found between the surface and the bottom compartment. All the microlitter fragments found were analysed through Fourier Transform Infrared Spectroscopy (FTIR). The comparison of the expected buoyancies of the polymers identified puth faith in the allocation of the species to the respective compartments. Therefore, considering the Marine Strategy Framework Directive objective, this approach could be useful in assessing microlitter distribution and composition vertically across the water column., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The genomic variation of the Italian peninsula populations is currently under characterised: the only Italian whole-genome reference is represented by the Tuscans from the 1000 Genome Project. To address this issue, we sequenced a total of 947 Italian samples from three different geographical areas. First, we defined a new Italian Genome Reference Panel (IGRP1.0) for imputation, which improved imputation accuracy, especially for rare variants, and we tested it by GWAS analysis on red blood traits. Furthermore, we extended the catalogue of genetic variation investigating the level of population structure, the pattern of natural selection, the distribution of deleterious variants and occurrence of human knockouts (HKOs). Overall the results demonstrate a high level of genomic differentiation between cohorts, different signatures of natural selection and a distinctive distribution of deleterious variants and HKOs, confirming the necessity of distinct genome references for the Italian population.