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

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.

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

10.1101/354159 ◽

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.

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MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA)

Genes ◽

10.3390/genes12101497 ◽

2021 ◽

Vol 12 (10) ◽

pp. 1497

Author(s):

Matthias Christen ◽

Henriëtte Booij-Vrieling ◽

Jelena Oksa-Minalto ◽

Cynthia de Vries ◽

Alexandra Kehl ◽

...

Keyword(s):

Vision Loss ◽

Sequence Data ◽

Mammalian Species ◽

Homozygosity Mapping ◽

Whole Genome Sequence ◽

Critical Interval ◽

Splice Defect ◽

Gene Encoding ◽

Functional Knowledge ◽

Er Export

We investigated a hereditary syndrome in Cane Corso dogs. Affected dogs developed dental-skeletal-retinal anomaly (DSRA), clinically characterized by brittle, discolored, translucent teeth, disproportionate growth and progressive retinal degeneration resulting in vision loss. Combined linkage and homozygosity mapping delineated a 5.8 Mb critical interval. The comparison of whole genome sequence data of an affected dog to 789 control genomes revealed a private homozygous splice region variant in the critical interval. It affected the MIA3 gene encoding the MIA SH3 domain ER export factor 3, which has an essential role in the export of collagen and other secreted proteins. The identified variant, XM_005640835.3:c.3822+3_3822+4del, leads to skipping of two exons from the wild type transcript, XM_005640835.3:r.3712_3822del. Genotypes at the variant were consistent with monogenic autosomal recessive mode of inheritance in a complete family and showed perfect genotype-phenotype association in 18 affected and 22 unaffected Cane Corso dogs. MIA3 variants had previously been shown to cause related phenotypes in humans and mice. Our data in dogs together with the existing functional knowledge of MIA3 variants in other mammalian species suggest the MIA3 splice defect and a near complete loss of gene function as causative molecular pathomechanism for the DSRA phenotype in the investigated dogs.

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A Missense Variant Affecting the C-Terminal Tail of UNC93B1 in Dogs with Exfoliative Cutaneous Lupus Erythematosus (ECLE)

Genes ◽

10.3390/genes11020159 ◽

2020 ◽

Vol 11 (2) ◽

pp. 159 ◽

Cited By ~ 1

Author(s):

Tosso Leeb ◽

Fabienne Leuthard ◽

Vidhya Jagannathan ◽

Sarah Kiener ◽

Anna Letko ◽

...

Keyword(s):

Lupus Erythematosus ◽

Sequence Data ◽

Transmembrane Protein ◽

Cutaneous Lupus Erythematosus ◽

Whole Genome Sequence ◽

Recessive Trait ◽

Critical Interval ◽

Mutant Genotype ◽

A Genome ◽

Cutaneous Lupus

Cutaneous lupus erythematosus (CLE) in humans encompasses multiple subtypes that exhibit a wide array of skin lesions and, in some cases, are associated with the development of systemic lupus erythematosus (SLE). We investigated dogs with exfoliative cutaneous lupus erythematosus (ECLE), a dog-specific form of chronic CLE that is inherited as a monogenic autosomal recessive trait. A genome-wide association study (GWAS) with 14 cases and 29 controls confirmed a previously published result that the causative variant maps to chromosome 18. Autozygosity mapping refined the ECLE locus to a 493 kb critical interval. Filtering of whole genome sequence data from two cases against 654 controls revealed a single private protein-changing variant in this critical interval, UNC93B1:c.1438C>A or p.Pro480Thr. The homozygous mutant genotype was exclusively observed in 23 ECLE affected German Shorthaired Pointers and an ECLE affected Vizsla, but absent from 845 controls. UNC93B1 is a transmembrane protein located in the endoplasmic reticulum and endolysosomes, which is required for correct trafficking of several Toll-like receptors (TLRs). The p.Pro480Thr variant is predicted to affect the C-terminal tail of the UNC93B1 that has recently been shown to restrict TLR7 mediated autoimmunity via an interaction with syndecan binding protein (SDCBP). The functional knowledge on UNC93B1 strongly suggests that p.Pro480Thr is causing ECLE in dogs. These dogs therefore represent an interesting spontaneous model for human lupus erythematosus. Our results warrant further investigations of whether genetic variants affecting the C-terminus of UNC93B1 might be involved in specific subsets of CLE or SLE cases in humans and other species.

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Identification ofKlebsiellacapsule synthesis loci from whole genome data

10.1101/071415 ◽

2016 ◽

Cited By ~ 3

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.

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Faculty Opinions recommendation of Optimal algorithms for haplotype assembly from whole-genome sequence data.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13339986.14707085 ◽

2011 ◽

Author(s):

Alejandro Schaffer

Keyword(s):

Genome Sequence ◽

Sequence Data ◽

Whole Genome Sequence ◽

Whole Genome ◽

Optimal Algorithms ◽

Genome Sequence Data ◽

Haplotype Assembly

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PSI-40 Two mitochondrial lineages revealed in North American yak

Journal of Animal Science ◽

10.1093/jas/skaa278.833 ◽

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.

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

Bioinformatics ◽

10.1093/bioinformatics/btab166 ◽

2021 ◽

Cited By ~ 1

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

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Whole genome sequence data of Bacillus australimaris strain B28A, isolated from Marine Water in India

Data in Brief ◽

10.1016/j.dib.2021.107240 ◽

2021 ◽

pp. 107240

Author(s):

Wael Ali Mohammed Hadi ◽

Boby T Edwin ◽

A Jayakumaran Nair

Keyword(s):

Genome Sequence ◽

Sequence Data ◽

Marine Water ◽

Whole Genome Sequence ◽

Whole Genome ◽

Genome Sequence Data

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

Virology Journal ◽

10.1186/s12985-021-01583-3 ◽

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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