Search results for "linkage"

The first high-density sequence characterized SNP-based linkage map of olive (Olea europaea L. subsp. europaea) developed using genotyping by sequenc…

2016

A number of linkage maps have been previously developed in olive; however, these are mostly composed of markers that have not been characterized at the sequence level, supplemented with smaller numbers of microsatellite markers. In this investigation, we sought to develop a saturated linkage mapping resource for olive composed entirely of sequence characterized markers. We employed genotyping by sequencing to develop a map of a F2 population derived from the selfing of the cultivar Koroneiki. The linkage map contained a total of 23 linkage groups comprised of 1,597 tagged SNP markers in 636 mapping bins spanning a genetic distance of 1189.7 cM. An additional 6,658 segregating SNPs were asso…

2018

Genome-Wide-Association-Studies have become a powerful method to link point mutations (e.g. single nucleotide polymorphisms (SNPs)) to a certain phenotype or a disease. However, their power to detect SNPs associated to polygenic diseases such as Alzheimer's Disease (AD) is limited, since they can only infer the pairwise relation of single SNPs to the phenotype and ignore possible effects of various SNP combinations. The common method to probe these possible complex genetic patterns is to compute a measure called linkage disequilibrium (LD). Despite the fact that several predictive patterns found with LD could successfully be applied to medical diagnosis, this measure still holds several dra…

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

2017

International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68…

The population genomics of archaeological transition in west Iberia: Investigation of ancient substructure using imputation and haplotype-based metho…

2017

We analyse new genomic data (0.05–2.95x) from 14 ancient individuals from Portugal distributed from the Middle Neolithic (4200–3500 BC) to the Middle Bronze Age (1740–1430 BC) and impute genomewide diploid genotypes in these together with published ancient Eurasians. While discontinuity is evident in the transition to agriculture across the region, sensitive haplotype-based analyses suggest a significant degree of local hunter-gatherer contribution to later Iberian Neolithic populations. A more subtle genetic influx is also apparent in the Bronze Age, detectable from analyses including haplotype sharing with both ancient and modern genomes, D-statistics and Y-chromosome lineages. However, t…

Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis

2017

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluat…

9q33.3q34.11 microdeletion: new contiguous gene syndrome encompassing STXBP1, LMX1B and ENG genes assessed using reverse phenotyping

2016

International audience; The increasing use of array-CGH in malformation syndromes with intellectual disability could lead to the description of new contiguous gene syndrome by the analysis of the gene content of the microdeletion and reverse phenotyping. Thanks to a national and international call for collaboration by Achropuce and Decipher, we recruited four patients carrying de novo overlapping deletions of chromosome 9q33.3q34.11, including the STXBP1, the LMX1B and the ENG genes. We restrained the selection to these three genes because the effects of their haploinsufficency are well described in the literature and easily recognizable clinically. All deletions were detected by array-CGH …

Association study of MMP8 gene in osteoarthritis.

2016

Objectives: Osteoarthritis (OA) is a joint disease common in the elderly. There is a prior functional evidence for different matrix metalloproteinases (MMPs), such as MMP8 and MMP9, having a role in the breakdown of cartilage extracellular matrix in OA. Thus, we analyzed whether the common genetic variants of MMP8 and MMP9 contribute to the risk of OA. Materials and methods: In total, 13 common tagging single-nucleotide polymorphisms (SNPs) were studied in a discovery knee OA cohort of 185 cases and 895 controls. For validation, two knee OA replication cohorts and two hand OA replication cohorts were studied (altogether 1369 OA cases, 4445 controls in the five cohorts). The chi(2) test for …

Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients.

2016

Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, lin…

Rett Syndrome Mutant Neural Cells Lacks MeCP2 Immunoreactive Bands.

2016

Dysfunctions of MeCP2 protein lead to various neurological disorders such as Rett syndrome and Autism. The exact functions of MeCP2 protein is still far from clear. At a molecular level, there exist contradictory data. MeCP2 protein is considered a single immunoreactive band around 75 kDa by western-blot analysis but several reports have revealed the existence of multiple MeCP2 immunoreactive bands above and below the level where MeCP2 is expected. MeCP2 immunoreactive bands have been interpreted in different ways. Some researchers suggest that multiple MeCP2 immunoreactive bands are unidentified proteins that cross-react with the MeCP2 antibody or degradation product of MeCP2, while others…

Genomic characterization of the Braque Français type Pyrénées dog and relationship with other breeds

2018

The evaluation of genetic variability is a useful research tool for the correct management of selection and conservation strategies in dog breeds. In addition to pedigree genealogies, genomic data allow a deeper knowledge of the variability and genetic structure of populations. To date, many dog breeds, such as small regional breeds, still remain uncharacterized. Braque Français type Pyrénées (BRA) is a dog breed originating from a very old type of gun-dog used for pointing the location of game birds to hunters. Despite the ancient background, the knowledge about levels of genetic diversity, degree of inbreeding and population structure is scarce. This may raise concerns on the possibility …