scholarly journals Seascape genomics of coastal bottlenose dolphins along strong gradients of temperature and salinity

2021 ◽  
Author(s):  
Eleanor Pratt ◽  
Luciano Beheregaray ◽  
Kerstin Bilgmann ◽  
Nikki Zanardo ◽  
Fernando Diaz-Aguirre ◽  
...  
Keyword(s):  
Kidney Development ◽  
Environmental Gradients ◽  
Bottlenose Dolphins ◽  
Large Population ◽  
Habitat Type ◽  
Enrichment Analysis ◽  
Adaptive Divergence ◽  
Nucleotide Polymorphisms ◽  
Natal Philopatry ◽  
Genomic Study

Heterogeneous seascapes and strong environmental gradients in coastal waters are expected to influence adaptive divergence, particularly in species with large population sizes where selection is expected to be highly efficient. However, these influences might also extend to species characterized by strong social structure, natal philopatry and small home ranges. We implemented a seascape genomic study to test this hypothesis in Indo-Pacific bottlenose dolphins (Tursiops aduncus) distributed along the environmentally heterogeneous coast of southern Australia. The datasets included oceanographic and environmental variables thought to be good predictors of local adaptation in dolphins and 8,081 filtered single nucleotide polymorphisms (SNPs) genotyped for individuals sampled from six different bioregions. From a neutral perspective, population structure and connectivity of the dolphins were generally influenced by habitat type and social structuring. Genotype-environment association analysis identified 241 candidate adaptive loci and revealed that sea surface temperature and salinity gradients influenced adaptive divergence in these animals at both large- (1,000s km) and fine-scales (<100 km). Enrichment analysis and annotation of candidate genes revealed functions related to sodium-activated ion transport, kidney development, adipogenesis and thermogenesis. The findings of spatial adaptive divergence and inferences of putative physiological adaptations challenge previous suggestions that marine megafauna is most likely to be affected by environmental and climatic changes via indirect, trophic effects. Our work contributes to conservation management of coastal bottlenose dolphins subjected to anthropogenic disturbance and to efforts of clarifying how seascape heterogeneity influences adaptive diversity and evolution in small cetaceans.

scholarly journals One Health Genomic Study of Human and Animal Klebsiella pneumoniae Isolated at Diagnostic Laboratories on a Small Caribbean Island

Antibiotics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 42
Author(s):  
Patrick Butaye ◽  
Marc Stegger ◽  
Arshnee Moodley ◽  
Peter Damborg ◽  
Andrea Williams ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
One Health ◽  
De Novo ◽  
Large Population ◽  
Vervet Monkeys ◽  
Nucleotide Polymorphisms ◽  
Caribbean Island ◽  
Indirect Contact ◽  
Genomic Study ◽  
Antimicrobial Resistance Gene

Klebsiella pneumoniae causes a variety of infections in both humans and animals. In this study, we characterised the genomes of human and animal isolates from two diagnostic laboratories on St. Kitts, a small Caribbean island inhabited by a large population of vervet monkeys. In view of the increased chances of direct or indirect contact with humans and other animal species, we used the One Health approach to assess transmission of K. pneumoniae across host species by sequencing 82 presumptive K. pneumoniae clinical isolates from humans (n = 51), vervets (n = 21), horses (n = 5), dogs (n = 4) and a cat (n = 1). Whole genome sequencing (WGS) was carried out using Illumina technology. De novo assembly was performed in CLC Genomics Workbench v.11.0. Single nucleotide polymorphisms were detected using NASP followed by phylogenetic analysis using IQ-TREE. Virulence and antimicrobial resistance gene contents were analysed using the Kleborate and CGE pipelines. WGS-based analysis showed that 72 isolates were K. pneumoniae sensu stricto and five K. quasipneumoniae and five K. variicola. K. pneumoniae isolates belonged to 35 sequence types (ST), three of which were occasionally shared between humans and animals: ST23, ST37 and ST307. The ST23 strains from vervets formed a separate cluster amongst publicly available sequenced ST23 strains, indicating the presence of a specific vervet sublineage. Animal strains harbored fewer resistance genes and displayed distinct virulence traits that appeared to be host-specific in vervet isolates. Our results show that K. pneumoniae infections on this Caribbean island are usually caused by host-specific lineages.

Role of the norepinephrine transporter polymorphisms in atomoxetine treatment: From response to side effects in children with ADHD

2021 ◽  
pp. 026988112110152
Author(s):  
Melike Kevser Gul ◽  
Elif Funda Sener ◽  
Muge Gulcihan Onal ◽  
Esra Demirci
Keyword(s):  
Side Effects ◽  
Treatment Response ◽  
Large Population ◽  
Norepinephrine Transporter ◽  
Response To Treatment ◽  
Nucleotide Polymorphisms ◽  
Children With Adhd ◽  
Real Time Quantitative Pcr ◽  
Treatment Side Effects ◽  
Adhd Treatment

Objective: Atomoxetine (ATX), one of the most commonly used drugs after stimulants in attention deficit hyperactivity disorder (ADHD) treatment, is an inhibitor of the norepinephrine transporter ( NET/SLC6A2), which is also associated with the etiology of ADHD. In this study, we aimed to investigate the effect of NET gene polymorphisms on response to ATX treatment and to find the answers to the questions about whether there is a relationship between the severity of the disorder and the observed side effects in children with ADHD. Method: About 100 children with ADHD and 80 healthy controls (HCs) were included in this study. The dose of ATX was started at 0.5 mg/kg/day and titrated at 1.2 mg/kg/day. Response to treatment of 78 patients was evaluated 2 months after the beginning of the treatment. After whole blood samples were obtained, DNAs were isolated, and samples were stored at −80°C. Two single-nucleotide polymorphisms (SNPs) (rs12708954 and rs3785143) were analyzed by real-time quantitative PCR (qRT-PCR). Results: The patients with both rs12708954 and rs3785143 heterozygous genotype had better treatment response and more side effects than patients with wild type. There was not found any association between any of the investigated NET polymorphisms and ADHD severity. Conclusion: It was, however, found that the NET rs12708954 and rs3785143 genotypes affect the treatment response to ATX in our study; thus, further studies with a large population are needed to understand the effects of NET polymorphisms on treatment, side effects, and also the severity of ADHD.

scholarly journals Identification and Functional Annotation of Genes Related to Bone Stability in Laying Hens Using Random Forests

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 702
Author(s):  
Simon Jansen ◽  
Ulrich Baulain ◽  
Christin Habig ◽  
Faisal Ramzan ◽  
Jens Schauer ◽  
...  
Keyword(s):  
Random Forests ◽  
Metabolic Pathways ◽  
Genetic Architecture ◽  
Laying Hens ◽  
Enrichment Analysis ◽  
Nucleotide Polymorphisms ◽  
Mineral Density ◽  
Single Nucleotide ◽  
Economic Problems ◽  
Close Proximity

Skeletal disorders, including fractures and osteoporosis, in laying hens cause major welfare and economic problems. Although genetics have been shown to play a key role in bone integrity, little is yet known about the underlying genetic architecture of the traits. This study aimed to identify genes associated with bone breaking strength and bone mineral density of the tibiotarsus and the humerus in laying hens. Potentially informative single nucleotide polymorphisms (SNP) were identified using Random Forests classification. We then searched for genes known to be related to bone stability in close proximity to the SNPs and identified 16 potential candidates. Some of them had human orthologues. Based on our findings, we can support the assumption that multiple genes determine bone strength, with each of them having a rather small effect, as illustrated by our SNP effect estimates. Furthermore, the enrichment analysis showed that some of these candidates are involved in metabolic pathways critical for bone integrity. In conclusion, the identified candidates represent genes that may play a role in the bone integrity of chickens. Although further studies are needed to determine causality, the genes reported here are promising in terms of alleviating bone disorders in laying hens.

148 Multiple Dysregulated Novel Pathways and Genes in Aleutian Mink Disease Revealed by Selection Signatures and Gene Network Analyses Using Whole-genome Sequence Data

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 76-76
Author(s):  
Seyed Milad Vahedi ◽  
Karim Karimi ◽  
Siavash Salek Ardestani ◽  
Younes Miar
Keyword(s):  
Sequence Data ◽  
American Mink ◽  
Enrichment Analysis ◽  
Whole Genome Sequence ◽  
Fixation Index ◽  
Pathway Enrichment Analysis ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Network Analyses ◽  
Genome Level

Abstract Aleutian disease (AD) is a chronic persistent infection in domestic mink caused by Aleutian mink disease virus (AMDV). Female mink’s fertility and pelt quality depression are the main reasons for the AD’s negative economic impacts on the mink industry. A total number of 79 American mink from the Canadian Center for Fur Animal Research at Dalhousie University (Truro, NS, Canada) were classified based on the results of counter immunoelectrophoresis (CIEP) tests into two groups of positive (n = 48) and negative (n = 31). Whole-genome sequences comprising 4,176 scaffolds and 8,039,737 single nucleotide polymorphisms (SNPs) were used to trace the selection footprints for response to AMDV infection at the genome level. Window-based fixation index (Fst) and nucleotide diversity (θπ) statistics were estimated to compare positive and negative animals’ genomes. The overlapped top 1% genomic windows between two statistics were considered as potential regions underlying selection pressures. A total of 98 genomic regions harboring 33 candidate genes were detected as selective signals. Most of the identified genes were involved in the development and functions of immune system (PPP3CA, SMAP2, TNFRSF21, SKIL, and AKIRIN2), musculoskeletal system (COL9A2, PPP1R9A, ANK2, AKAP9, and STRIT1), nervous system (ASCL1, ZFP69B, SLC25A27, MCF2, and SLC7A14), reproductive system (CAMK2D, GJB7, SSMEM1, C6orf163), liver (PAH and DPYD), and lung (SLC35A1). Gene-expression network analysis showed the interactions among 27 identified genes. Moreover, pathway enrichment analysis of the constructed genes network revealed significant oxytocin (KEGG: hsa04921) and GnRH signaling (KEGG: hsa04912) pathways, which are likely to be impaired by AMDV leading to dams’ fecundity reduction. These results provided a perspective to the genetic architecture of response to AD in American mink and novel insight into the pathogenesis of AMDV.

scholarly journals TADA – a Machine Learning Tool for Functional Annotation based Prioritisation of Putative Pathogenic CNVs

2020 ◽  
Author(s):  
J. Hertzberg ◽  
S. Mundlos ◽  
M. Vingron ◽  
G. Gallone
Keyword(s):  
Machine Learning ◽  
Functional Annotation ◽  
Copy Number Variants ◽  
Enrichment Analysis ◽  
Computational Prediction ◽  
Nucleotide Polymorphisms ◽  
Automated Classification ◽  
Single Nucleotide ◽  
Pathogenic Cnvs ◽  
Disease Impact

AbstractThe computational prediction of disease-associated genetic variation is of fundamental importance for the genomics, genetics and clinical research communities. Whereas the mechanisms and disease impact underlying coding single nucleotide polymorphisms (SNPs) and small Insertions/Deletions (InDels) have been the focus of intense study, little is known about the corresponding impact of structural variants (SVs), which are challenging to detect, phase and interpret. Few methods have been developed to prioritise larger chromosomal alterations such as Copy Number Variants (CNVs) based on their pathogenicity. We address this issue with TADA, a method to prioritise pathogenic CNVs through manual filtering and automated classification, based on an extensive catalogue of functional annotation supported by rigorous enrichment analysis. We demonstrate that our machine-learning classifiers for deletions and duplications are able to accurately predict pathogenic CNVs (AUC: 0.8042 and 0.7869, respectively) and produce a well-calibrated pathogenicity score. The combination of enrichment analysis and classifications suggests that prioritisation of pathogenic CNVs based on functional annotation is a promising approach to support clinical diagnostic and to further the understanding of mechanisms that control the disease impact of larger genomic alterations.

scholarly journals Multiple functional variants in the IL1RL1 region are pretransplant markers for risk of GVHD and infection deaths

2019 ◽  
Vol 3 (16) ◽  
pp. 2512-2524 ◽  
Author(s):  
Ezgi Karaesmen ◽  
Theresa Hahn ◽  
Alexander James Dile ◽  
Abbas A. Rizvi ◽  
Junke Wang ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Fixed Effects ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Nucleotide Polymorphisms ◽  
Protein Levels ◽  
Risk Alleles ◽  
Functional Variants ◽  
Genomic Study ◽  
Meta Analyses

Abstract Graft-versus-host disease (GVHD) and infections are the 2 main causes of death without relapse after allogeneic hematopoietic cell transplantation (HCT). Elevated soluble serum simulation-2 (sST2), the product of IL1RL1 in plasma/serum post-HCT, is a validated GVHD biomarker. Hundreds of SNPs at 2q12.1 have been shown to be strongly associated with sST2 concentrations in healthy populations. We therefore hypothesized that the donor genetic variants in IL1RL1 correlate with sST2 protein levels associated with patient survival outcomes after HCT. We used DISCOVeRY-BMT (Determining the Influence of Susceptibility Conveying Variants Related to 1-Year Mortality after Blood and Marrow Transplantation), a genomic study of &gt;3000 donor–recipient pairs, to inform our hypothesis. We first measured pre-HCT plasma/serum sST2 levels in a subset of DISCOVeRY-BMT donors (n = 757) and tested the association of donor sST2 levels with donor single nucleotide polymorphisms (SNPs) in the 2q12.1 region. Donor SNPs associated with sST2 levels were then tested for association with recipient death caused by acute GVHD (aGVHD)–, infection-, and transplant-related mortality in cohorts 1 and 2. Meta-analyses of cohorts 1 and 2 were performed using fixed-effects inverse variance weighting, and P values were corrected for multiple comparisons. Donor risk alleles in rs22441131 (Pmeta = .00026) and rs2310241 (Pmeta = .00033) increased the cumulative incidence of aGVHD death up to fourfold and were associated with high sST2 levels. Donor risk alleles at rs4851601 (Pmeta = 9.7 × 10−7), rs13019803 (Pmeta = 8.9 × 10−6), and rs13015714 (Pmeta = 5.3 × 10−4) increased cumulative incidence of infection death to almost sevenfold and were associated with low sST2 levels. These functional variants are biomarkers of infection or aGVHD death and could facilitate donor selection, prophylaxis, and a conditioning regimen to reduce post-HCT mortality.

scholarly journals Regional imaging genetic enrichment analysis

2019 ◽  
Vol 36 (8) ◽  
pp. 2554-2560
Author(s):  
Xiaohui Yao ◽  
Shan Cong ◽  
Jingwen Yan ◽  
Shannon L Risacher ◽  
Andrew J Saykin ◽  
...  
Keyword(s):  
Statistical Power ◽  
Enrichment Analysis ◽  
Genetic Effects ◽  
Imaging Genetics ◽  
Supplementary Information ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Specific Expression ◽  
Positron Emission ◽  
Annotation Information

Abstract Motivation Brain imaging genetics aims to reveal genetic effects on brain phenotypes, where most studies examine phenotypes defined on anatomical or functional regions of interest (ROIs) given their biologically meaningful interpretation and modest dimensionality compared with voxelwise approaches. Typical ROI-level measures used in these studies are summary statistics from voxelwise measures in the region, without making full use of individual voxel signals. Results In this article, we propose a flexible and powerful framework for mining regional imaging genetic associations via voxelwise enrichment analysis, which embraces the collective effect of weak voxel-level signals and integrates brain anatomical annotation information. Our proposed method achieves three goals at the same time: (i) increase the statistical power by substantially reducing the burden of multiple comparison correction; (ii) employ brain annotation information to enable biologically meaningful interpretation and (iii) make full use of fine-grained voxelwise signals. We demonstrate our method on an imaging genetic analysis using data from the Alzheimer’s Disease Neuroimaging Initiative, where we assess the collective regional genetic effects of voxelwise FDG-positron emission tomography measures between 116 ROIs and 565 373 single-nucleotide polymorphisms. Compared with traditional ROI-wise and voxelwise approaches, our method identified 2946 novel imaging genetic associations in addition to 33 ones overlapping with the two benchmark methods. In particular, two newly reported variants were further supported by transcriptome evidences from region-specific expression analysis. This demonstrates the promise of the proposed method as a flexible and powerful framework for exploring imaging genetic effects on the brain. Availability and implementation The R code and sample data are freely available at https://github.com/lshen/RIGEA. Supplementary information Supplementary data are available at Bioinformatics online.

Inheritance of geographic variation in body size, and countergradient variation in growth rates, in the southern brown bandicoot Isoodon obesulus.

2000 ◽  
Vol 22 (1) ◽  
pp. 9 ◽  
Author(s):  
ML Hale
Keyword(s):  
Growth Rate ◽  
Body Weight ◽  
Body Size ◽  
Geographic Variation ◽  
Growth Rates ◽  
Habitat Type ◽  
Adaptive Divergence ◽  
Common Environment ◽  
Countergradient Variation ◽  
Large Animals

The inheritance of geographic variation in body size in the southern brown bandicoot (Isoodon obesulus) was investigated through a common-environment crossbreeding experiment. The geographic variation in body size is related to habitat type, suggesting that it may be adaptive. Adults from two locations in Western Australia, Perth (large animals) and Albany (small animals), were collected and offspring from both hybrid and non-hybrid matings were reared under controlled conditions. All four variables examined (head length, pes length, ear length and body weight) were found to possess a large genetic component, supporting the interpretation that the geographic variation in size is adaptive. The three length variables initially showed additive genetic variation, although the variation in body weight displayed dominance. Genetically controlled differences in growth rate were also detected, with the smaller animals, found in the relatively poorer environment, possessing the faster intrinsic growth rate. Thus, not only does there appear to be adaptive divergence in initial body size, but the countergradient variation in growth rates provides additional evidence for adaptive divergence in this species.

scholarly journals QTL × environment interactions underlie adaptive divergence in switchgrass across a large latitudinal gradient

2019 ◽  
Vol 116 (26) ◽  
pp. 12933-12941 ◽  
Author(s):  
David B. Lowry ◽  
John T. Lovell ◽  
Li Zhang ◽  
Jason Bonnette ◽  
Philip A. Fay ◽  
...  
Keyword(s):  
Local Adaptation ◽  
Panicum Virgatum ◽  
Environmental Gradients ◽  
Adaptive Divergence ◽  
Multiple Loci ◽  
Trade Offs ◽  
Locally Adaptive ◽  
Trait Locus ◽  
Benefits And Costs ◽  
Transplant Experiments

Local adaptation is the process by which natural selection drives adaptive phenotypic divergence across environmental gradients. Theory suggests that local adaptation results from genetic trade-offs at individual genetic loci, where adaptation to one set of environmental conditions results in a cost to fitness in alternative environments. However, the degree to which there are costs associated with local adaptation is poorly understood because most of these experiments rely on two-site reciprocal transplant experiments. Here, we quantify the benefits and costs of locally adaptive loci across 17° of latitude in a four-grandparent outbred mapping population in outcrossing switchgrass (Panicum virgatumL.), an emerging biofuel crop and dominant tallgrass species. We conducted quantitative trait locus (QTL) mapping across 10 sites, ranging from Texas to South Dakota. This analysis revealed that beneficial biomass (fitness) QTL generally incur minimal costs when transplanted to other field sites distributed over a large climatic gradient over the 2 y of our study. Therefore, locally advantageous alleles could potentially be combined across multiple loci through breeding to create high-yielding regionally adapted cultivars.

scholarly journals A Genomic Study of Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniels

Animals ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1895
Author(s):  
Arianna Bionda ◽  
Matteo Cortellari ◽  
Mara Bagardi ◽  
Stefano Frattini ◽  
Alessio Negro ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Heart Development ◽  
Mitral Valve Disease ◽  
Transforming Growth Factor ◽  
Valve Disease ◽  
Fixation Index ◽  
Nucleotide Polymorphisms ◽  
Extended Haplotype ◽  
Polygenic Inheritance ◽  
Genomic Study

Cavalier King Charles spaniels (CKCSs) show the earliest onset and the highest incidence of myxomatous mitral valve disease (MMVD). Previous studies have suggested a polygenic inheritance of the disease in this breed and revealed an association with regions on canine chromosomes 13 and 14. Following clinical and echocardiographic examinations, 33 not-directly-related CKCSs were selected and classified as cases (n = 16) if MMVD was present before 5 years of age or as controls (n = 17) if no or very mild MMVD was present after 5 years of age. DNA was extracted from whole blood and genotyped with a Canine 230K SNP BeadChip instrument. Cases and controls were compared with three complementary genomic analyses (Wright’s fixation index—FST, cross-population extended haplotype homozygosity—XP-EHH, and runs of homozygosity—ROH) to identify differences in terms of heterozygosity and regions of homozygosity. The top 1% single-nucleotide polymorphisms (SNPs) were selected and mapped, and the genes were thoroughly investigated. Ten consensus genes were found localized on chromosomes 3-11-14-19, partially confirming previous studies. The HEPACAM2, CDK6, and FAH genes, related to the transforming growth factor β (TGF-β) pathway and heart development, also emerged in the ROH analysis. In conclusion, this work expands the knowledge of the genetic basis of MMVD by identifying genes involved in the early onset of MMVD in CKCSs.

Sign in / Sign up

Export Citation Format

Share Document