65 research outputs found
A Nonsense Variant in the ST14 Gene in Akhal-Teke Horses with Naked Foal Syndrome
No full textNaked foal syndrome (NFS) is a genodermatosis in the Akhal-Teke horse breed. We provide the first scientific description of this phenotype. Affected horses have almost no hair and show a mild ichthyosis. So far, all known NFS affected horses died between a few weeks and 3 yr of age. It is not clear whether a specific pathology caused the premature deaths. NFS is inherited as a monogenic autosomal recessive trait. We mapped the disease causing genetic variant to two segments on chromosomes 7 and 27 in the equine genome. Whole genome sequencing of two affected horses, two obligate carriers, and 75 control horses from other breeds revealed a single nonsynonymous genetic variant on the chromosome 7 segment that was perfectly associated with NFS. The affected horses were homozygous for ST14:c.388G>T, a nonsense variant that truncates >80% of the open reading frame of the ST14 gene (p.Glu130*). The variant leads to partial nonsense-mediated decay of the mutant transcript. Genetic variants in the ST14 gene are responsible for autosomal recessive congenital ichthyosis 11 in humans. Thus, the identified equine ST14:c.388G>T variant is an excellent candidate causative variant for NFS, and the affected horses represent a large animal model for a known human genodermatosis. Our findings will enable genetic testing to avoid the nonintentional breeding of NFS-affected foals
Analysis of ROH patterns in the Noriker horse breed reveals signatures of selection for coat color and body size
No full textSupplementary data for publication: Grilz-Seger G, Druml T, Neuditschko M, Mesaric M, Cotman M, Brem. (2019). Analysis of ROH patterns in the Noriker horse breed reveals signatures of selection for coat color and body size. Anim Genet. 2019 Aug;50(4):334-346
Analysis of ROH patterns in the Noriker horse breed reveals signatures of selection for coat color and body size
No full textSupplementary data for publication: Grilz-Seger G, Druml T, Neuditschko M, Mesaric M, Cotman M, Brem. (2019). Analysis of ROH patterns in the Noriker horse breed reveals signatures of selection for coat color and body size. Anim Genet. 2019 Aug;50(4):334-346
Analysis of ROH patterns in the Noriker horse breed reveals signatures of selection for coat color and body size
No full textSupplementary data for publication: Grilz-Seger G, Druml T, Neuditschko M, Mesaric M, Cotman M, Brem. (2019). Analysis of ROH patterns in the Noriker horse breed reveals signatures of selection for coat color and body size. Anim Genet. 2019 Aug;50(4):334-346
A genome-wide association study for equine recurrent airway obstruction in European Warmblood horses reveals a suggestive new quantitative trait locus on chromosome 13.
No full textRecurrent airway obstruction (RAO), also known as heaves, is an asthma-like respiratory disease. Its development is strongly influenced by environmental risk factors such as sensitization and exposure to moldy hay, straw bedding and stabling indoors. A hereditary component has been documented in previous studies; however, so far no causative genetic variant that influences the risk of developing RAO has been identified. In this study, we revised an existing dataset and selected 384 horses for genotyping on the Affymetrix high-density equine SNP array. We performed an allelic case-control genome-wide association study, which revealed a suggestively significant association on equine chromosome 13 at 32 843 309 bp. This SNP is located in the protein-coding gene TXNDC11, which is possibly involved in the folding process of the multiprotein complexes DUOX1 and DUOX2. In humans, these proteins are known to take part in regulating the production of H2 O2 in the respiratory tract epithelium as well as in MUC5AC mucin expression. Therefore, TXNDC11 may be considered a functional candidate gene, and further research is needed to explore its potential role in RAO-affected horses
Selection signatures in Shetland ponies.
No full textShetland ponies were selected for numerous traits including small stature, strength, hardiness and longevity. Despite the different selection criteria, Shetland ponies are well known for their small stature. We performed a selection signature analysis including genome-wide SNPs of 75 Shetland ponies and 76 large-sized horses. Based upon this dataset, we identified a selection signature on equine chromosome (ECA) 1 between 103.8 Mb and 108.5 Mb. A total of 33 annotated genes are located within this interval including the IGF1R gene at 104.2 Mb and the ADAMTS17 gene at 105.4 Mb. These two genes are well known to have a major impact on body height in numerous species including humans. Homozygosity mapping in the Shetland ponies identified a region with increased homozygosity between 107.4 Mb and 108.5 Mb. None of the annotated genes in this region have so far been associated with height. Thus, we cannot exclude the possibility that the identified selection signature on ECA1 is associated with some trait other than height, for which Shetland ponies were selected
An Organometallic Gold(I) Bis-N-Heterocyclic Carbene Complex with Multimodal Activity in Ovarian Cancer Cells
No full textThe organometallic AuI bis-N-heterocyclic carbene complex [Au(9-methylcaffeine-8-ylidene)2]+ (AuTMX2) was previously shown to selectively and potently stabilise telomeric DNA G-quadruplex (G4) structures. This study sheds light on the molecular reactivity and mode of action of AuTMX2 in the cellular context using mass spectrometry-based methods, including shotgun proteomics in A2780 ovarian cancer cells. In contrast to other metal-based anticancer agents, this organogold compound is less prone to form coordinative bonds with biological nucleophiles and is expected to exert its drug effects mainly by non-covalent interactions. Global protein expression changes of treated cancer cells revealed a multimodal mode of action of AuTMX2 by alterations in the nucleolus, telomeres, actin stress-fibres and stress-responses, which were further supported by pharmacological assays, fluorescence microscopy and cellular accumulation experiments. Proteomic data are available via ProteomeXchange with identifier PXD020560
Sequence-based genome-wide association studies reveal the polygenic architecture of Varroa destructor resistance in Western honey bees Apis mellifera
No full textDatasetThis repository contains data linked to the publication: Sequence-based genome-wide association studies reveal the polygenic architecture of Varroa destructor resistance in Western honey bees Apis mellifera by SE Eynard, F Mondet, B Basso, O Bouchez, T Bulach, Y Le Conte, B Dainat, A Decourtye, L Genestout, M Guichard, F Guillaume, E Labarthe, B Locke, R Mahla, J de Miranda, M Neuditschko, F Phocas, Y Poquet, C Sann, RF Serre, K Tabet, A Vignal and B Servin [Preprint] (2024). https://doi.org/10.1101/2024.02.16.580755. It includes a file summarising the sequence availability on SRA, the phenotypes, the 'count' files produced using popoolation 2 from mpileup files, the summary statistics from the GWAS analysis performed for a unique population and phenotype using GEMMA and the fixed version, 15/03/2024, of the scripts available on GitHub (https://github.com/seynard/gwas_beestrong
Using Whole-Genome Sequence Information to Foster Conservation Efforts for the European Dark Honey Bee, Apis mellifera mellifera
No full textPas de Clé UTInternational audiencePollination is a key ecosystem service for agricultural systems and Western honey bees, Apis mellifera, are the most important managed pollinators. Major losses of managed honey bee colonies reinforced the need to take advantage of locally adapted subspecies and ecotypes to buffer populations against various stressors. However, introductions of non-native honey bees from distant lineages are likely to undermine respective conservation efforts unless reliable and cost effective tools can be used to identify hybridization. The purpose of this study is to characterize current population structure and genetic diversity, and to assess the degree of admixture between native and introduced honey bees. Moreover, we aim to select a reduced number of genetic markers to improve conservation management strategies. We take advantage of recent developments in next-generation sequencing and network-based clustering to investigate conservation efforts for the native European Dark honey bee, A. m. mellifera, which is threatened by introgression in most of its range. We collected whole-genome sequence information from haploid drones of A. m. mellifera, A. m. carnica, and Buckfast sampled throughout Switzerland (N = 81), as well as from four Swiss A. m. mellifera conservation areas (N = 39) and from one conservatory in the French Alps (N = 31). Population structure analyses based upon 3.375 M genome-wide SNPs discerned samples by subspecies and geographic origin (Switzerland or France). Ancestry inference indicated admixed individuals in all of the protected areas, calling for improved management efforts. After testing different subsets of ancestry informative SNPs using three different selection strategies (FST, PCA-based or at random), as few as 50 SNPs are found to be sufficient to differentiate native from introduced honey bees. Therefore, our data suggests that a low-density SNP panel can be a precise and cost-effective tool to support conservation management efforts for managed pollinators
Genome-wide association studies based on sequence-derived genotypes reveal new QTL associated with conformation and performance traits in the Franches-Montagnes horse breed
No full textTo identify novel quantitative trait loci (QTL) within horses, we performed genome-wide association studies (GWAS) based on sequence-level genotypes for conformation and performance traits in the Franches-Montagnes (FM) horse breed. Sequence-level genotypes of FM horses were derived by re-sequencing 30 key founders and imputing 50K data of genotyped horses. In total, we included 1077 FM horses genotyped for ~4 million SNPs and their respective de-regressed breeding values of the traits in the analysis. Based on this dataset, we identified a total of 14 QTL associated with 18 conformation traits and one performance trait. Therefore, our results suggest that the application of sequence-derived genotypes increases the power to identify novel QTL which were not identified previously based on 50K SNP chip data
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