Search results for "polymorph"

Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes

2021

Survival in high-risk neuroblastoma (HR-NB) patients remains poor despite multimodal treatment. We aimed to identify HR-NB patients with worse outcomes by analyzing the genomic instability derived from segmental chromosomal aberrations. We calculated 3 genomic instability indexes for primary tumor SNP array profiles from 127 HR-NB patients: (1) Copy number aberration burden (%gainslength+%losseslength), (2) copy number load (CNL) (%gainslength-%losseslength) and (3) net genomic load (NGL) (%gainsamount-%lossesamount). Tumors were classified according to positive or negative CNL and NGL genomic subtypes. The impact of the genomic instability indexes on overall survival (OS) was assessed with…

Genomic characterization of the Atlantic cod sex-locus

2016

AbstractA variety of sex determination mechanisms can be observed in evolutionary divergent teleosts. Sex determination is genetic in Atlantic cod (Gadus morhua), however the genomic location or size of its sex-locus is unknown. Here, we characterize the sex-locus of Atlantic cod using whole genome sequence (WGS) data of 227 wild-caught specimens. Analyzing more than 55 million polymorphic loci, we identify 166 loci that are associated with sex. These loci are located in six distinct regions on five different linkage groups (LG) in the genome. The largest of these regions, an approximately 55 Kb region on LG11, contains the majority of genotypes that segregate closely according to a XX-XY s…

KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern

2019

BACKGROUND: The presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown. METHODS: To identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry. RESULTS: We identified a genome-wide significant (P < 5 × 10(–8)) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discov…

Sex and MC1R variants in human pigmentation: Differences in tanning ability and sensitivity to sunlight between sexes

2016

Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

2016

Background BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (…

Mitochondrial genetic haplogroups and cardiovascular diseases: Data from the Osteoarthritis Initiative

2019

Background Some case-control studies reported that mitochondrial haplogroups could be associated with the onset of cardiovascular diseases (CVD), but the literature regarding this topic is limited. We aimed to investigate whether any mitochondrial haplogroup carried a higher or lower risk of CVD in a large cohort of North American people affected by knee osteoarthritis or at high risk for this condition. Materials and methods A longitudinal cohort study including individuals from the Osteoarthritis Initiative was done. Haplogroups were assigned through a combination of sequencing and PCR-RFLP techniques. All the mitochondrial haplogroups have been named following this nomenclature: HV, JT, …

Genomic and Metabolomic Profile Associated to Clustering of Cardio-Metabolic Risk Factors

2016

Background To identify metabolomic and genomic markers associated with the presence of clustering of cardiometabolic risk factors (CMRFs) from a general population. Methods and Findings One thousand five hundred and two subjects, Caucasian, > 18 years, representative of the general population, were included. Blood pressure measurement, anthropometric parameters and metabolic markers were measured. Subjects were grouped according the number of CMRFs (Group 1: <2; Group 2: 2; Group 3: 3 or more CMRFs). Using SNPlex, 1251 SNPs potentially associated to clustering of three or more CMRFs were analyzed. Serum metabolomic profile was assessed by 1H NMR spectra using a Brucker Advance DRX 600 spect…

Genome- wide association study with additional genetic and post-transcriptional analyses reveals novel regulators of plasma factor XI levels

2017

International audience; Coagulation factor XI (FXI) has become increasingly interesting for its role in pathogenesis of thrombosis. While elevated plasma levels of FXI have been associated with venous thromboembolism and ischemic stroke, its deficiency is associated with mild bleeding. We aimed to determine novel genetic and post-transcriptional plasma FXI regulators.We performed a genome-wide association study (GWAS) for plasma FXI levels, using novel data imputed to the 1000 Genomes reference panel. Individual GWAS analyses, including a total of 16,169 European individuals from the ARIC, GHS, MARTHA and PROCARDIS studies, were meta-analysed and further replicated in 2,045 individuals from…

Prevalence of pathogenic copy number variants among children conceived by donor oocyte.

2021

AbstractDevelopment of assisted reproductive technologies to address infertility has favored the birth of many children in the last years. The majority of children born with these treatments are healthy, but some concerns remain on the safety of these medical procedures. We have retrospectively analyzed both the fertilization method and the microarray results in all those children born between 2010 and 2019 with multiple congenital anomalies, developmental delay and/or autistic spectrum disorder (n = 486) referred for array study in our center. This analysis showed a significant excess of pathogenic copy number variants among those patients conceived after in vitro fertilization with donor …

Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors

2020

Abstract Objectives This study evaluated the emergence of mutations associated with integrase strand transfer inhibitors (INSTI) resistance (INSTI-RMs) and the integrase evolution in human immunodeficiency virus type 1 (HIV-1) infected patients treated with this drug class. Methods The emergence of INSTI-RMs and integrase evolution (estimated as genetic distance between integrase sequences under INSTI treatment and before INSTI treatment) were evaluated in 107 INSTI-naive patients (19 drug-naive and 88 drug-experienced) with two plasma genotypic resistance tests: one before INSTI treatment and one under INSTI treatment. A logistic regression analysis was performed to evaluate factors associ…