scholarly journals Sequence variability, constraint and selection in the CD163 gene in pigs

2018 ◽  
Author(s):  
Martin Johnsson ◽  
Roger Ros-Freixedes ◽  
Gregor Gorjanc ◽  
Matt A. Campbell ◽  
Sudhir Naswa ◽  
...  
Keyword(s):  
Sequence Data ◽  
Haplotype Diversity ◽  
Whole Genome Sequence ◽  
Respiratory Syndrome Virus ◽  
Evolutionary Constraint ◽  
Selective Sweeps ◽  
Sequence Variability ◽  
Protein Coding ◽  
Knock Out ◽  
Deep Survey

AbstractBackgroundIn this paper, we investigate sequence variability, evolutionary constraint, and selection on the CD163 gene in pigs. The pig CD163 gene is required for infection by porcine reproductive and respiratory syndrome virus (PRRSV), a serious pathogen with major impact on pig production.ResultsWe used targeted pooled sequencing of the exons of CD163 to detect sequence variants in 35,000 pigs of diverse genetic backgrounds and search for potential knock-out variants. We then used whole genome sequence data from three pig lines to calculate a variant intolerance score, which measures the tolerance of genes to protein coding variation, a selection test on protein coding variation over evolutionary time, and haplotype diversity statistics to detect recent selective sweeps during breeding.ConclusionsWe performed a deep survey of sequence variation in the CD163 gene in domestic pigs. We found no potential knock-out variants. CD163 was moderately intolerant to variation, and showed evidence of positive selection in the lineage leading up to the pig, but no evidence of selective sweeps during breeding.

scholarly journals Deletion of the SELENOP gene leads to CNS atrophy with cerebellar ataxia in dogs

PLoS Genetics ◽  
2021 ◽  
Vol 17 (8) ◽  
pp. e1009716
Author(s):  
Matthias Christen ◽  
Sandra Högler ◽  
Miriam Kleiter ◽  
Michael Leschnik ◽  
Corinna Weber ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Sequence Data ◽  
Clinical Signs ◽  
Selenium Deficiency ◽  
Homozygosity Mapping ◽  
Whole Genome Sequence ◽  
Critical Interval ◽  
Protein Coding ◽  
Knock Out ◽  
Homozygous Mutant

We investigated a hereditary cerebellar ataxia in Belgian Shepherd dogs. Affected dogs developed uncoordinated movements and intention tremor at two weeks of age. The severity of clinical signs was highly variable. Histopathology demonstrated atrophy of the CNS, particularly in the cerebellum. Combined linkage and homozygosity mapping in a family with four affected puppies delineated a 52 Mb critical interval. The comparison of whole genome sequence data of one affected dog to 735 control genomes revealed a private homozygous structural variant in the critical interval, chr4:66,946,539_66,963,863del17,325. This deletion includes the entire protein coding sequence of SELENOP and is predicted to result in complete absence of the encoded selenoprotein P required for selenium transport into the CNS. Genotypes at the deletion showed the expected co-segregation with the phenotype in the investigated family. Total selenium levels in the blood of homozygous mutant puppies of the investigated litter were reduced to about 30% of the value of a homozygous wildtype littermate. Genotyping >600 Belgian Shepherd dogs revealed an additional homozygous mutant dog. This dog also suffered from pronounced ataxia, but reached an age of 10 years. Selenop-/- knock-out mice were reported to develop ataxia, but their histopathological changes were less severe than in the investigated dogs. Our results demonstrate that deletion of the SELENOP gene in dogs cause a defect in selenium transport associated with CNS atrophy and cerebellar ataxia (CACA). The affected dogs represent a valuable spontaneous animal model to gain further insights into the pathophysiological consequences of CNS selenium deficiency.

scholarly journals Diversity of The Ornate Lorikeet (Trichoglossus ornatus) Birds Based on Mitochondrial DNA Protein Coding Gene

2018 ◽  
Vol 10 (2) ◽  
pp. 465-471
Author(s):  
Dwi Astuti ◽  
Siti Nuramaliati Prijono
Keyword(s):  
Mitochondrial Dna ◽  
Dna Sequences ◽  
Sequence Data ◽  
Gene Diversity ◽  
Haplotype Diversity ◽  
Base Pairs ◽  
Protein Coding ◽  
Dna Sequence Data ◽  
Breeding Management ◽  
Nd2 Gene

Ornate lorikeet (Trichoglossus ornatus) is an endemic bird in Sulawesi. Endemism is one of the factors in declining bird’s population. In the case of the birds conservation programme, information about gene diversity is important for basic strategy. Mitochondrial DNA of animals consists of protein coding genes including ND2 gene. This study informs diversity of the Ornate Lorikeet (Trichoglossus ornatus) birds based on DNA sequences of ND2 gene. DNA total was extracted from blood samples of 21 birds. PCR (Polymerase Chain Reaction) was performed and successfully amplified a single DNA fragment of ND2 gene for all birds. DNA fragments were sequenced and totally 997 base pairs were analyzed. NJ tree was constructed using MEGA5. All DNA sequence data showed that between the birds there were 20  polymorphic (segregating) sites with mean genetic distance was 0.004 ± 0.002 (ranged from 0,000 – 0,008), and had 17 sequence haplotypes (HTor1- HTo17). Haplotype diversity (Hd) was 0.967 ± 0.30387 and nucleotide diversity (Pi) was 0.00439 ± 0.0012. Genetic diversity information could be potential relevance to the breeding management for conservation of the birds.

scholarly journals Identification ofKlebsiellacapsule synthesis loci from whole genome data

2016 ◽  
Author(s):  
Kelly L. Wyres ◽  
Ryan R. Wick ◽  
Claire Gorrie ◽  
Adam Jenney ◽  
Rainer Follador ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Sequence Data ◽  
Gene Clusters ◽  
Whole Genome Sequence ◽  
Multi Drug Resistance ◽  
Reference Database ◽  
Whole Genome ◽  
Genome Sequences ◽  
Protein Coding ◽  
Genome Data

AbstractBackgroundKlebsiella pneumoniaeand close relatives are a growing cause of healthcare-associated infections for which increasing rates of multi-drug resistance are a major concern. TheKlebsiellapolysaccharide capsule is a major virulence determinant and epidemiological marker. However, little is known about capsule epidemiology since serological typing is not widely accessible, and many isolates are serologically non-typeable. Molecular methods for capsular typing are needed, but existing methods lack sensitivity and specificity and fail to take advantage of the information available in whole-genome sequence data, which is increasingly being generated for surveillance and investigation ofKlebsiella.MethodsWe investigated the diversity of capsule synthesis loci (K loci) among a large, diverse collection of 2503 genome sequences ofK. pneumoniaeand closely related species. We incorporated analyses of both full-length K locus DNA sequences and clustered protein coding sequences to identify, annotate and compare K locus structures, and we propose a novel method for identifying K loci based on full locus information extracted from whole genome sequences.ResultsA total of 134 distinct K loci were identified, including 31 novel types. Comparative analysis of K locus gene content detected 508 unique protein coding gene clusters that appear to reassort via homologous recombination, generating novel K locus types. Extensive nucleotide diversity was detected among thewziandwzcgenes, both within and between K loci, indicating that current typing schemes based on these genes are inadequate. As a solution, we introduceKaptive, a novel software tool that automates the process of identifying K loci from large sets ofKlebsiellagenomes based on full locus information.ConclusionsThis work highlights the extensive diversity ofKlebsiellaK loci and the proteins that they encode. We propose a standardised K locus nomenclature forKlebsiella, present a curated reference database of all known K loci, and introduce a tool for identifying K loci from genome data (https://github.com/katholt/Kaptive). These developments constitute important new resources for theKlebsiellacommunity for use in genomic surveillance and epidemiology.

Sporadic Occurrence of Recent Selective Sweeps from Standing Variation in Humans as Revealed by an Approximate Bayesian Computation Approach

Genetics ◽  
2021 ◽  
Author(s):  
Guillaume Laval ◽  
Etienne Patin ◽  
Pierre Boutillier ◽  
Lluis Quintana-Murci
Keyword(s):  
Approximate Bayesian Computation ◽  
Sequence Data ◽  
Machine Learning Algorithms ◽  
Whole Genome Sequence ◽  
Bayesian Computation ◽  
Human Adaptation ◽  
Selective Sweeps ◽  
Standing Variation ◽  
Genome Wide ◽  
Approximate Bayesian

Abstract During their dispersals over the last 100,000 years, modern humans have been exposed to a large variety of environments, resulting in genetic adaptation. While genome-wide scans for the footprints of positive Darwinian selection have increased knowledge of genes and functions potentially involved in human local adaptation, they have globally produced evidence of a limited contribution of selective sweeps in humans. Conversely, studies based on machine learning algorithms suggest that recent sweeps from standing variation are widespread in humans, an observation that has been recently questioned. Here, we sought to formally quantify the number of recent selective sweeps in humans, by leveraging approximate Bayesian computation and whole-genome sequence data. Our computer simulations revealed suitable ABC estimations, regardless of the frequency of the selected alleles at the onset of selection and the completion of sweeps. Under a model of recent selection from standing variation, we inferred that an average of 68 (from 56 to 79) and 140 (from 94 to 198) sweeps occurred over the last 100,000 years of human history, in African and Eurasian populations, respectively. The former estimation is compatible with human adaptation rates estimated since divergence with chimps, and reveal numbers of sweeps per generation per site in the range of values estimated in Drosophila. Our results confirm the rarity of selective sweeps in humans and show a low contribution of sweeps from standing variation to recent human adaptation.

scholarly journals PSI-40 Two mitochondrial lineages revealed in North American yak

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 477-477
Author(s):  
Leah K Treffer ◽  
Edward S Rice ◽  
Anna M Fuller ◽  
Samuel Cutler ◽  
Jessica L Petersen
Keyword(s):  
Sequence Data ◽  
Haplotype Network ◽  
Ovis Aries ◽  
Similar Species ◽  
Nucleotide Polymorphisms ◽  
Mt Dna ◽  
Protein Coding ◽  
Sister Clade ◽  
Mtdna Sequence ◽  
The Impact

Abstract Domestic yak (Bos grunniens) are bovids native to the Asian Qinghai-Tibetan Plateau. Studies of Asian yak have revealed that introgression with domestic cattle has contributed to the evolution of the species. When imported to North America (NA), some hybridization with B. taurus did occur. The objective of this study was to use mitochondrial (mt) DNA sequence data to better understand the mtDNA origin of NA yak and their relationship to Asian yak and related species. The complete mtDNA sequence of 14 individuals (12 NA yak, 1 Tibetan yak, 1 Tibetan B. indicus) was generated and compared with sequences of similar species from GeneBank (B. indicus, B. grunniens (Chinese), B. taurus, B. gaurus, B. primigenius, B. frontalis, Bison bison, and Ovis aries). Individuals were aligned to the B. grunniens reference genome (ARS_UNL_BGru_maternal_1.0), which was also included in the analyses. The mtDNA genes were annotated using the ARS-UCD1.2 cattle sequence as a reference. Ten unique NA yak haplotypes were identified, which a haplotype network separated into two clusters. Variation among the NA haplotypes included 93 nonsynonymous single nucleotide polymorphisms. A maximum likelihood tree including all taxa was made using IQtree after the data were partitioned into twenty-two subgroups using PartitionFinder2. Notably, six NA yak haplotypes formed a clade with B. indicus; the other four haplotypes grouped with B. grunniens and fell as a sister clade to bison, gaur and gayal. These data demonstrate two mitochondrial origins of NA yak with genetic variation in protein coding genes. Although these data suggest yak introgression with B. indicus, it appears to date prior to importation into NA. In addition to contributing to our understanding of the species history, these results suggest the two major mtDNA haplotypes in NA yak may functionally differ. Characterization of the impact of these differences on cellular function is currently underway.

TIGER: inferring DNA replication timing from whole-genome sequence data

2021 ◽  
Author(s):  
Amnon Koren ◽  
Dashiell J Massey ◽  
Alexa N Bracci
Keyword(s):  
Dna Replication ◽  
Genome Sequence ◽  
Genomic Dna ◽  
Sequence Data ◽  
Replication Timing ◽  
Whole Genome Sequence ◽  
Supplementary Information ◽  
Whole Genome ◽  
Genome Sequence Data ◽  
Dna Replication Timing

Abstract Motivation Genomic DNA replicates according to a reproducible spatiotemporal program, with some loci replicating early in S phase while others replicate late. Despite being a central cellular process, DNA replication timing studies have been limited in scale due to technical challenges. Results We present TIGER (Timing Inferred from Genome Replication), a computational approach for extracting DNA replication timing information from whole genome sequence data obtained from proliferating cell samples. The presence of replicating cells in a biological specimen leads to non-uniform representation of genomic DNA that depends on the timing of replication of different genomic loci. Replication dynamics can hence be observed in genome sequence data by analyzing DNA copy number along chromosomes while accounting for other sources of sequence coverage variation. TIGER is applicable to any species with a contiguous genome assembly and rivals the quality of experimental measurements of DNA replication timing. It provides a straightforward approach for measuring replication timing and can readily be applied at scale. Availability and Implementation TIGER is available at https://github.com/TheKorenLab/TIGER. Supplementary information Supplementary data are available at Bioinformatics online

scholarly journals Whole-Genome Sequence Analysis of Pseudorabies Virus Clinical Isolates from Pigs in China between 2012 and 2017 in China

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1322
Author(s):  
Ruiming Hu ◽  
Leyi Wang ◽  
Qingyun Liu ◽  
Lin Hua ◽  
Xi Huang ◽  
...  
Keyword(s):  
Selection Pressure ◽  
Pseudorabies Virus ◽  
Viral Evolution ◽  
Infectious Agent ◽  
Genomic Diversity ◽  
Whole Genome Sequence ◽  
Evolutionary Constraint ◽  
The Novel ◽  
Novel Variants ◽  
Pressure Analysis

Pseudorabies virus (PRV) is an economically significant swine infectious agent. A PRV outbreak took place in China in 2011 with novel virulent variants. Although the association of viral genomic variability with pathogenicity is not fully confirmed, the knowledge concerning PRV genomic diversity and evolution is still limited. Here, we sequenced 54 genomes of novel PRV variants isolated in China from 2012 to 2017. Phylogenetic analysis revealed that China strains and US/Europe strains were classified into two separate genotypes. PRV strains isolated from 2012 to 2017 in China are highly related to each other and genetically close to classic China strains such as Ea, Fa, and SC. RDP analysis revealed 23 recombination events within novel PRV variants, indicating that recombination contributes significantly to the viral evolution. The selection pressure analysis indicated that most ORFs were under evolutionary constraint, and 19 amino acid residue sites in 15 ORFs were identified under positive selection. Additionally, 37 unique mutations were identified in 19 ORFs, which distinguish the novel variants from classic strains. Overall, our study suggested that novel PRV variants might evolve from classical PRV strains through point mutation and recombination mechanisms.

scholarly journals Genome sequences of human cytomegalovirus strain TB40/E variants propagated in fibroblasts and epithelial cells

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Ahmed Al Qaffas ◽  
Salvatore Camiolo ◽  
Mai Vo ◽  
Alexis Aguiar ◽  
Amine Ourahmane ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Cytomegalovirus ◽  
Viral Entry ◽  
Sequence Data ◽  
Laboratory Strain ◽  
Serial Passage ◽  
Wild Type Virus ◽  
Protein Coding ◽  
Genetic Changes ◽  
Long Read

AbstractThe advent of whole genome sequencing has revealed that common laboratory strains of human cytomegalovirus (HCMV) have major genetic deficiencies resulting from serial passage in fibroblasts. In particular, tropism for epithelial and endothelial cells is lost due to mutations disrupting genes UL128, UL130, or UL131A, which encode subunits of a virion-associated pentameric complex (PC) important for viral entry into these cells but not for entry into fibroblasts. The endothelial cell-adapted strain TB40/E has a relatively intact genome and has emerged as a laboratory strain that closely resembles wild-type virus. However, several heterogeneous TB40/E stocks and cloned variants exist that display a range of sequence and tropism properties. Here, we report the use of PacBio sequencing to elucidate the genetic changes that occurred, both at the consensus level and within subpopulations, upon passaging a TB40/E stock on ARPE-19 epithelial cells. The long-read data also facilitated examination of the linkage between mutations. Consistent with inefficient ARPE-19 cell entry, at least 83% of viral genomes present before adaptation contained changes impacting PC subunits. In contrast, and consistent with the importance of the PC for entry into endothelial and epithelial cells, genomes after adaptation lacked these or additional mutations impacting PC subunits. The sequence data also revealed six single noncoding substitutions in the inverted repeat regions, single nonsynonymous substitutions in genes UL26, UL69, US28, and UL122, and a frameshift truncating gene UL141. Among the changes affecting protein-coding regions, only the one in UL122 was strongly selected. This change, resulting in a D390H substitution in the encoded protein IE2, has been previously implicated in rendering another viral protein, UL84, essential for viral replication in fibroblasts. This finding suggests that IE2, and perhaps its interactions with UL84, have important functions unique to HCMV replication in epithelial cells.

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