Sequence variants associated with resilient responses in growing pigs.

The current work aimed to identify genomic regions and candidate genes associated with resilience in pigs. In previous work, we proposed the body weight deviation from the expected growth curve (ΔBW) and the increase of the positive acute-phase protein haptoglobin (ΔHP) after a vaccine challenge as resilience indicators which may be improved through selective breeding in pigs. Individuals with steady growth rate and minor activation of haptoglobin (high ΔBW and low ΔHP values) were considered resilient.

Genetic Association Studies in Host-Pathogen Interaction Analysis.

Studying host-pathogen interactions at a molecular level has always been technically challenging. Identifying the different biochemical and genetic pathways involved in the different stages of infection traditionally require complex molecular biology tools and often the use of costly animal models. In this chapter, we illustrate a complementary approach to address host-pathogen interactions, taking advantage of the natural interindividual genetic diversity.

Polygenic risk score comparator (PRScomp): Test population vs. worldwide populations.

Background: Polygenic risk scores (PRS) are a powerful tool for predicting an individual's genetic risk for complex diseases.

Methods: We have developed a web service (PRScomp) as a user-friendly tool to evaluate PRS of the user own population and compare it with worldwide populations.

Results: A disease/trait database has been constructed from GWAS Catalog summary statistics.

Buffy coat signatures of breast cancer risk in a prospective cohort study.

Background: Epigenetic alterations are a near-universal feature of human malignancy and have been detected in malignant cells as well as in easily accessible specimens such as blood and urine. These findings offer promising applications in cancer detection, subtyping, and treatment monitoring. However, much of the current evidence is based on findings in retrospective studies and may reflect epigenetic patterns that have already been influenced by the onset of the disease.

The power of geohistorical boundaries for modeling the genetic background of human populations: The case of the rural catalan Pyrenees.

The genetic variation of the European population at a macro-geographic scale follows genetic gradients which reflect main migration events. However, less is known about factors affecting mating patterns at a micro-geographic scale. In this study we have analyzed 726,718 autosomal single nucleotide variants in 435 individuals from the catalan Pyrenees covering around 200 km of a vast and abrupt region in the north of the Iberian Peninsula, for which we have information about the geographic origin of all grand-parents and parents.

Identification of as a Novel AKT Activator from a Lung Cancer Epigenome-Wide Association Study (EWAS).

Changes in DNA methylation identified by epigenome-wide association studies (EWAS) have been recently linked to increased lung cancer risk. However, the cellular effects of these differentially methylated positions (DMPs) are often unclear. Therefore, we investigated top differentially methylated positions identified from an EWAS study.

Differentially methylated regions within lung cancer risk loci are enriched in deregulated enhancers.

Genome-wide association studies (GWAS) have identified SNPs linked with lung cancer risk. Our aim was to discover the genes, non-coding RNAs, and regulatory elements within GWAS-identified risk regions that are deregulated in non-small cell lung carcinoma (NSCLC) to identify novel, clinically targetable genes and mechanisms in carcinogenesis. A targeted bisulphite-sequencing approach was used to comprehensively investigate DNA methylation changes occurring within lung cancer risk regions in 17 NSCLC and adjacent normal tissue pairs.

Lack of protective effect of chloroquine derivatives on COVID-19 disease in a Spanish sample of chronically treated patients.

Background: The search for a SARS-CoV-2 treatment has emerged as a worldwide priority. We evaluated the role of chloroquine and its derivatives in COVID-19 in Spanish individuals.

Methods: We performed a survey addressed to patients regularly taking chloroquine and its derivatives for the control of their autoimmune diseases.

Toll-Like Receptor 2 Promoter -196 to -174 Deletion Affects CD4 Levels Along Human Immunodeficiency Virus Infection Progression.

Toll-like receptor 2 (TLR2) plays a key role in innate immune response recognizing molecular patterns expressed by pathogens. rs111200466 is a TLR2 promoter insertion/deletion polymorphism with contradictory data about its role in human immunodeficiency virus type 1 (HIV-1) infection. We analyzed rs111200466 in HIV-1 disease progression and showed a correlation with a faster progression to the CD4+ < 200 cells/μL outcome for deletion allele carriers (Cox regression analysis: hazard ratio, 2.

Resilience Effects of and DNA Markers during PRRSV Outbreaks in Reproductive Sows.

The porcine reproductive and respiratory syndrome virus (PRRSV) is a major infectious stressor that causes serious health problems and productivity drops. Based on previous genome-wide analyses, we selected and as candidate genes for resilience, and genotyped three mutations, including a 3'UTR variant SGK1_rs338508371 and two synonymous variants TAP1_rs1109026889 and TAP1_rs80928141 in 305 Landrace × Large White sows. All polymorphisms affected the reproductive performance in the outbreak, but not during the endemic phase, thereby indicating a potential use of these markers for resilience.

Genetic associations of the vitamin D and antiviral pathways with natural resistance to HIV-1 infection are influenced by interpopulation variability.

Vitamin D (VitD) may modulate anti-HIV-1 responses modifying the risk to acquire the HIV-1-infection. We performed a nested case-control exploratory study involving 413 individuals; HIV-1-exposed seropositives (cases) and seronegatives (HESN) (controls) from three cohorts: sexually-exposed from Colombia and Italy and parenterally-exposed from Spain. The association and interactions of 139 variants in 9 VitD pathway genes, and in 14 antiviral genes with resistance/susceptibility (R/S) to HIV-1 infection was evaluated.

Vitamin D Receptor polymorphisms and risk of enveloped virus infection: A meta-analysis.

Introduction: Vitamin-D plays a role regulating the immune response against to viral infection. In this sense, vitamin-D deficiency may confer increased susceptibility to enveloped virus infection such as HIV, Hepatitis, Dengue and Respiratory Syncytial virus infection, among others. Vitamin D activity is mediated by its receptor (VDR), which acts as a transcription factor modulating the expression of genes triggering the response against viruses.

Pleiotropic Analysis of Lung Cancer and Blood Triglycerides.

Epidemiologically related traits may share genetic risk factors, and pleiotropic analysis could identify individual loci associated with these traits. Because of their shared epidemiological associations, we conducted pleiotropic analysis of genome-wide association studies of lung cancer (12 160 lung cancer case patients and 16 838 control subjects) and cardiovascular disease risk factors (blood lipids from 188 577 subjects, type 2 diabetes from 148 821 subjects, body mass index from 123 865 subjects, and smoking phenotypes from 74 053 subjects). We found that 6p22.

Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer.

We conducted imputation to the 1000 Genomes Project of four genome-wide association studies of lung cancer in populations of European ancestry (11,348 cases and 15,861 controls) and genotyped an additional 10,246 cases and 38,295 controls for follow-up. We identified large-effect genome-wide associations for squamous lung cancer with the rare variants BRCA2 p.Lys3326X (rs11571833, odds ratio (OR) = 2.

Vitamin-D pathway genes and HIV-1 disease progression in injection drug users.

Vitamin-D has pleiotropic effects on calcium and bone metabolism, cellular growth control, cell differentiation and modulation of both innate and acquired immune response. Previous studies revealed the association of vitamin-D receptor gene (VDR) polymorphism with infection diseases including HIV-1 infection. To assess for association between polymorphisms of vitamin-D pathway genes CYP27B1, vitamin-D binding protein (VDBP) and VDR with HIV-1 infection, disease progression to acquired immunodeficiency syndrome (AIDS) was analysed according to CDC93 criteria in a cohort of 185 HIV-1 seroprevalent patients belonging to the injection drug users.

Absence of substantial copy number differences in a pair of monozygotic twins discordant for features of autism spectrum disorder.

Autism spectrum disorder (ASD) is a highly heritable disease (~0.9) with a complex genetic etiology. It is initially characterized by altered cognitive ability which commonly includes impaired language and communication skills as well as fundamental deficits in social interaction.

Association of BST-2 gene variants with HIV disease progression underscores the role of BST-2 in HIV type 1 infection.

We tested bone marrow stromal cell antigen 2 (BST-2) gene variants rs3217318, a 19-base-pair insertion/deletion polymorphism in the promoter region, and rs10415893, a tag single-nucleotide polymorphism in the 3' untranslated region, for their association with human immunodeficiency virus type 1 (HIV-1) infection and disease progression. The study included 356 subjects exposed to HIV-1 (185 with and 171 without infection) and 188 controls. The first decrease in the CD4(+) T-cell count to <200 cells/µL was used as the primary outcome, whereas the primary outcome plus initiation of any antiretroviral treatment was used as a secondary composite outcome.

Distribution of functional polymorphic variants of inflammation-related genes RANTES and CCR5 in long-lived individuals.

Although persistent inflammation has been related to unsuccessful aging, a pro-inflammatory status is the common phenotype in older people. To assess for a genetic component in the inflammatory status of the oldest we studied the distribution of two polymorphic chemokine pathway genes, RANTES and CCR5, in elderly. RANTES -403G/A and RANTES Int1.

Tagging long-lived individuals through vitamin-D receptor (VDR) haplotypes.

Longevity is a complex phenomenon involving multiple environmental and biological factors. Genetic studies of longevity have focussed on DNA repair, oxidative damage correction and immune-related genes. Vitamin-D works by modulating mineral homeostasis and key physiological processes such as cell proliferation and immune response.