Variation of the 3'RR1 HS1.2 Enhancer and Its Genomic Context.

In humans, the HS1.2 enhancer in the Ig heavy-chain locus is modular, with length polymorphism. Previous studies have shown the following features for this variation: (i) strong population structuring; (ii) association with autoimmune diseases; and (iii) association with developmental changes in Ig expression.

COVID-19 annual update: a narrative review.

Three and a half years after the pandemic outbreak, now that WHO has formally declared that the emergency is over, COVID-19 is still a significant global issue. Here, we focus on recent developments in genetic and genomic research on COVID-19, and we give an outlook on state-of-the-art therapeutical approaches, as the pandemic is gradually transitioning to an endemic situation. The sequencing and characterization of rare alleles in different populations has made it possible to identify numerous genes that affect either susceptibility to COVID-19 or the severity of the disease.

Genetics: A Starting Point for the Prevention and the Treatment of Obesity.

Obesity is a common, serious, and costly disease. More than 1 billion people worldwide are obese-650 million adults, 340 million adolescents, and 39 million children. The WHO estimates that, by 2025, approximately 167 million people-adults and children-will become less healthy because they are overweight or obese.

Indole-3-carbinol in vitro antiviral activity against SARS-Cov-2 virus and in vivo toxicity.

The effects of indole-3-carbinol (I3C) compound have been described deeply as antitumor drug in multiple cancers. Herein, I3C compound was tested for toxicity and antiviral activity against SARS-CoV-2 infection. Antiviral activity was assessed in vitro in both in VeroE6 cell line and human Lung Organoids (hLORGs) where I3C exhibited a direct anti-SARS-CoV-2 replication activity with an antiviral effect and a modulation of the expression of genes implicated in innate immunity and inflammatory response was observed at 16.

COVID-19 2022 update: transition of the pandemic to the endemic phase.

COVID-19, which is caused by the SARS-CoV-2, has ravaged the world for the past 2 years. Here, we review the current state of research into the disease with focus on its history, human genetics and genomics and the transition from the pandemic to the endemic phase. We are particularly concerned by the lack of solid information from the initial phases of the pandemic that highlighted the necessity for better preparation to face similar future threats.

COVID-19 and Molecular Genetics.

Since early December 2019, the COVID-19 pandemic has impacted global society: over 400 million people have been infected with SARS-CoV-2, and there have been nearly 6 million deaths worldwide (1 [...

Breast cancer in West Africa: molecular analysis of BRCA genes in early-onset breast cancer patients in Burkina Faso.

Background: Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths among women in Africa after cervical cancer. Even if the epidemiological data are now aligned with those relating to industrialized countries, the knowledge concerning breast cancer in Africa, particularly in Western Africa, still lack clinical data, medical treatments, and the evaluation of genetic and non-genetic factors implicated in the etiology of the disease. The early onset and the aggressiveness of diagnosed breast cancers in patients of African ancestry strongly suggest that the genetic risk factor may be a key component, but so far, very few studies on the impact of germ line mutations in breast cancer in Africa have been conducted, with negative consequences on prevention, awareness and patient management.

Will GWAS eventually allow the identification of genomic biomarkers for COVID-19 severity and mortality?

GWAS involve testing genetic variants across the genomes of many individuals to identify genotype-phenotype associations. GWAS have enabled the identification of numerous genomic biomarkers in various complex human diseases, including infectious ones. However, few of these studies are relevant for clinical practice or at the bedside.

COVID-19 one year into the pandemic: from genetics and genomics to therapy, vaccination, and policy.

COVID-19 has engulfed the world and it will accompany us all for some time to come. Here, we review the current state at the milestone of 1 year into the pandemic, as declared by the WHO (World Health Organization). We review several aspects of the on-going pandemic, focusing first on two major topics: viral variants and the human genetic susceptibility to disease severity.

Inhibition of HECT E3 ligases as potential therapy for COVID-19.

SARS-CoV-2 is responsible for the ongoing world-wide pandemic which has already taken more than two million lives. Effective treatments are urgently needed. The enzymatic activity of the HECT-E3 ligase family members has been implicated in the cell egression phase of deadly RNA viruses such as Ebola through direct interaction of its VP40 Protein.

COVID-19 update: the first 6 months of the pandemic.

The COVID-19 pandemic is sweeping the world and will feature prominently in all our lives for months and most likely for years to come. We review here the current state 6 months into the declared pandemic. Specifically, we examine the role of the pathogen, the host and the environment along with the possible role of diabetes.

COVID-19 and Genetic Variants of Protein Involved in the SARS-CoV-2 Entry into the Host Cells.

The recent global COVID-19 public health emergency is caused by SARS-CoV-2 infections and can manifest extremely variable clinical symptoms. Host human genetic variability could influence susceptibility and response to infection. It is known that ACE2 acts as a receptor for this pathogen, but the viral entry into the target cell also depends on other proteins.

HLA allele frequencies and susceptibility to COVID-19 in a group of 99 Italian patients.

With the aim to individuate alleles that may reflect a higher susceptibility to the disease, in the present study we analyzed the HLA allele frequency distribution in a group of 99 Italian patients affected by a severe or extremely severe form of COVID-19. After the application of Bonferroni's correction for multiple tests, a significant association was found for HLA-DRB1*15:01, -DQB1*06:02 and -B*27:07, after comparing the results to a reference group of 1017 Italian individuals, previously typed in our laboratory. The increased frequencies observed may contribute to identify potential markers of susceptibility to the disease, although controversial results on the role of single HLA alleles in COVID-19 patients have been recently reported.

Genetics and Genomics of Breast Cancer: update and translational perspectives.

In the recent years the rapid scientific innovation in the evaluation of the individual's genome have allowed the identification of variants associated with the onset, treatment and prognosis of various pathologies including cancer, and with a potential impact in the assessment of therapy responses. Despite the analysis and interpretation of genomic information is considered incomplete, in many cases the identification of specific genomic profile has allowed the stratification of subgroups of patients characterized by a better response to drug therapies. Individual genome analysis has changed profoundly the diagnostic and therapeutic approach of breast cancer in the last 15 years by identifying selective molecular lesions that drive the development of neoplasms, showing that each tumor has its own genomic signature, with some specific features and some features common to several sub-types.

Precision Medicine in Non-Communicable Diseases.

The increase in life expectancy during the 20th century ranks as one of society's greatest achievements, with massive growth in the numbers and proportion of the elderly, virtually occurring in every country of the world. The burden of chronic diseases is one of the main consequences of this phenomenon, severely hampering the quality of life of elderly people and challenging the efficiency and sustainability of healthcare systems. Non-communicable diseases (NCDs) are considered a global emergency responsible for over 70% of deaths worldwide.

Pro-oncogenic action of LOX-1 and its splice variant LOX-1Δ4 in breast cancer phenotypes.

The identification of new predictive biomarkers and therapeutic target for tailored therapy in breast cancer onset and progression is an interesting challenge. OLR-1 gene encodes the cell membrane receptor LOX-1 (lectin-like oxidized low-density lipoprotein receptor). We have recently identified a novel alternative OLR-1 isoform, LOX-1Δ4, whose expression and functions are still not clarified.

Star-related lipid transfer protein 10 (STARD10): a novel key player in alcohol-induced breast cancer progression.

Background: Ethanol abuse promotes breast cancer development, metastasis and recurrence stimulating mammary tumorigenesis by mechanisms that remain unclear. Normally, 35% of breast cancer is Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2)-positive that predisposes to poor prognosis and relapse, while ethanol drinking leads to invasion of their ERBB2 positive cells triggering the phosphorylation status of mitogen-activated protein kinase. StAR-related lipid transfer protein 10 (STARD10) is a lipid transporter of phosphatidylcholine (PC) and phosphatidylethanolamine (PE); changes on membrane composition of PC and PE occur before the morphological tumorigenic events.

Genetic Testing and Clinical Management Practices for Variants in Non-BRCA1/2 Breast (and Breast/Ovarian) Cancer Susceptibility Genes: An International Survey by the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Clinical Working Group.

Purpose: To describe a snapshot of international genetic testing practices, specifically regarding the use of multigene panels, for hereditary breast/ovarian cancers. We conducted a survey through the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium, covering questions about 16 non-/ genes.

Methods: Data were collected via in-person and paper/electronic surveys.

Deletion of REXO1L1 locus in a patient with malabsorption syndrome, growth retardation, and dysmorphic features: a novel recognizable microdeletion syndrome?

Background: Copy number variations (CNVs) can contribute to genetic variation among individuals and/or have a significant influence in causing diseases. Many studies consider new CNVs' effects on protein family evolution giving rise to gene duplicates or losses. "Unsuccessful" duplicates that remain in the genome as pseudogenes often exhibit functional roles.

Identification and characterization of functional risk variants for colorectal cancer mapping to chromosome 11q23.1.

Genome-wide association studies of colorectal cancer (CRC) have identified a number of common variants associated with modest risk, including rs3802842 at chromosome 11q23.1. Several genes map to this region but rs3802842 does not map to any known transcribed or regulatory sequences.

Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins.

The muscleblind-like (Mbnl) family of RNA-binding proteins plays important roles in muscle and eye development and in myotonic dystrophy (DM), in which expanded CUG or CCUG repeats functionally deplete Mbnl proteins. We identified transcriptome-wide functional and biophysical targets of Mbnl proteins in brain, heart, muscle, and myoblasts by using RNA-seq and CLIP-seq approaches. This analysis identified several hundred splicing events whose regulation depended on Mbnl function in a pattern indicating functional interchangeability between Mbnl1 and Mbnl2.

SOS1 over-expression in genital skin fibroblasts from hirsute women: a putative role of the SOS1/RAS pathway in the pathogenesis of hirsutism.

Hirsutism is the development of androgen-dependent terminal body hair in women in places in which terminal hair are normally not found. It is often associated with hyperandrogenemia and/or polycystic ovary syndrome (PCOS), but the existence of uncommom hirsutism forms that are not related to altered androgen plasma levels lead also to the definition of - idiopathic hirsutism. Although the pathophysiology of hirsutism has been linked to increasing 5-alpha reductase (SRD5A) activity and to an alteration of the androgen receptor (AR) transcriptional machinery, many aspects remain unclear.