Journal Articles
Permanent URI for this collectionhttps://mro.massey.ac.nz/handle/10179/7915
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Item Survey of functional Mendelian variants in New Zealand Huntaway and Heading dog breeds(John Wiley and Sons Ltd on behalf of Stichting International Foundation for Animal Genetics, 2025-10-01) Smith F; Lopdell T; Stephen M; Henry M; Dittmer K; Hunt H; Sneddon N; Williams L; Rolfe J; Garrick D; Littlejohn MDNew Zealand (NZ) Huntaway and Heading dogs are working breeds that play active roles on farms across NZ. While these breeds are common in NZ, they are not well-known elsewhere, and little is understood about their genetic make-up. Here, we used whole genome sequencing to provide a comprehensive genomic view of 249 working dogs. As first use of this resource, we report the allele frequencies of provisionally functional variants aggregated from the Online Mendelian Inheritance in Animals (OMIA) database. Of 435 “probably causal” variants, 27 segregated in our sample. Notable examples of disease variants potentially actionable for selection include those in the CUBN, CLN8, SGSH, SOD1, VWF, and VPS13B genes. These findings will enable genetic testing and selection opportunities to help improve the health and performance of future generations of these unique breeds.Item The Host Adaptation of Staphylococcus aureus to Farmed Ruminants in New Zealand, With Special Reference to Clonal Complex 1(John Wiley and Sons Ltd, 2025-06) Nesaraj J; Grinberg A; Laven R; Chanyi R; Altermann E; Bandi C; Biggs PJGenetic features of host adaptation of S. aureus to ruminants have been extensively studied, but the extent to which this adaptation occurs in nature remains unknown. In New Zealand, clonal complex 1 (CC1) is among the most common lineages in humans and the dominant lineage in cattle, enabling between-, and within-CC genomic comparisons of epidemiologically cohesive samples of isolates. We assessed the following genomic benchmarks of host adaptation to ruminants in 277 S. aureus from cattle, small ruminants, humans, and pets: 1, phylogenetic clustering of ruminant strains; 2, abundance of homo-specific ruminant-adaptive factors, and 3, scarcity of heterospecific factors. The genomic comparisons were complemented by comparative analyses of the metabolism of carbon sources that abound in ruminant milk. We identified features fulfilling the three benchmarks in virtually all ruminant isolates, including CC1. Data suggest the virulomes adapt to the ruminant niche sensu lato accross CCs. CC1 forms a ruminant-adapted clade that appears better equipped to utilise milk carbon sources than human CC1. Strain flow across the human–ruminant interface appears to only occur occasionally. Taken together, the results suggest a specialisation, rather than mere adaptation, clarifying why zoonotic and zoo-anthroponotic S. aureus transmission between ruminants and humans has hardly ever been reported.Item SeroBA: rapid high-throughput serotyping of Streptococcus pneumoniae from whole genome sequence data.(Microbiology Society, 2018-06-15) Epping L; van Tonder AJ; Gladstone RA; The Global Pneumococcal Sequencing Consortium; Bentley SD; Page AJ; Keane JAStreptococcus pneumoniae is responsible for 240 000-460 000 deaths in children under 5 years of age each year. Accurate identification of pneumococcal serotypes is important for tracking the distribution and evolution of serotypes following the introduction of effective vaccines. Recent efforts have been made to infer serotypes directly from genomic data but current software approaches are limited and do not scale well. Here, we introduce a novel method, SeroBA, which uses a k-mer approach. We compare SeroBA against real and simulated data and present results on the concordance and computational performance against a validation dataset, the robustness and scalability when analysing a large dataset, and the impact of varying the depth of coverage on sequence-based serotyping. SeroBA can predict serotypes, by identifying the cps locus, directly from raw whole genome sequencing read data with 98 % concordance using a k-mer-based method, can process 10 000 samples in just over 1 day using a standard server and can call serotypes at a coverage as low as 15-21×. SeroBA is implemented in Python3 and is freely available under an open source GPLv3 licence from: https://github.com/sanger-pathogens/seroba.Item Association of common and rare variants with Alzheimer's disease in more than 13,000 diverse individuals with whole-genome sequencing from the Alzheimer's Disease Sequencing Project.(Wiley Periodicals LLC on behalf of Alzheimer's Association, 2024-10-20) Lee W-P; Choi SH; Shea MG; Cheng P-L; Dombroski BA; Pitsillides AN; Heard-Costa NL; Wang H; Bulekova K; Kuzma AB; Leung YY; Farrell JJ; Lin H; Kunkle BW; Naj A; Blue EE; Nusetor F; Wang D; Boerwinkle E; Bush WS; Zhang X; De Jager PL; Dupuis J; Farrer LA; Fornage M; Martin E; Pericak-Vance M; Seshadri S; Wijsman EM; Wang L-S; Alzheimer's Disease Sequencing Project; Schellenberg GD; Destefano AL; Haines JL; Peloso GMINTRODUCTION Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous. METHODS We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data. RESULTS Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10−8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p = 1.9 × 10−9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p = 7.2 × 10−8). DISCUSSION We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD. Highlights We determine the association of genetic variants with Alzheimer's disease (AD) using 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data. We identified genetic variants at apolipoprotein E (APOE), BIN1, PSEN1, and LINC00320 associated with AD. We observed rare non-coding variants in the promoter of TOMM40 distinct of APOE.Item Genomic and clinical characteristics of campylobacteriosis in Australia.(Microbiology Society, 2024-01) Cribb DM; Moffatt CRM; Wallace RL; McLure AT; Bulach D; Jennison AV; French N; Valcanis M; Glass K; Kirk MDCampylobacter spp. are a common cause of bacterial gastroenteritis in Australia, primarily acquired from contaminated meat. We investigated the relationship between genomic virulence characteristics and the severity of campylobacteriosis, hospitalisation, and other host factors.We recruited 571 campylobacteriosis cases from three Australian states and territories (2018-2019). We collected demographic, health status, risk factors, and self-reported disease data. We whole genome sequenced 422 C. jejuni and 84 C. coli case isolates along with 616 retail meat isolates. We classified case illness severity using a modified Vesikari scoring system, performed phylogenomic analysis, and explored risk factors for hospitalisation and illness severity.On average, cases experienced a 7.5 day diarrhoeal illness with additional symptoms including stomach cramps (87.1 %), fever (75.6 %), and nausea (72.0 %). Cases aged ≥75 years had milder symptoms, lower Vesikari scores, and higher odds of hospitalisation compared to younger cases. Chronic gastrointestinal illnesses also increased odds of hospitalisation. We observed significant diversity among isolates, with 65 C. jejuni and 21 C. coli sequence types. Antimicrobial resistance genes were detected in 20.4 % of isolates, but multidrug resistance was rare (0.04 %). Key virulence genes such as cdtABC (C. jejuni) and cadF were prevalent (>90 % presence) but did not correlate with disease severity or hospitalisation. However, certain genes (e.g. fliK, Cj1136, and Cj1138) appeared to distinguish human C. jejuni cases from food source isolates.Campylobacteriosis generally presents similarly across cases, though some are more severe. Genotypic virulence factors identified in the literature to-date do not predict disease severity but may differentiate human C. jejuni cases from food source isolates. Host factors like age and comorbidities have a greater influence on health outcomes than virulence factors.Item A frameshift-deletion mutation in Reelin causes cerebellar hypoplasia in White Swiss Shepherd dogs(John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics, 2023-10) Littlejohn MD; Sneddon N; Dittmer K; Keehan M; Stephen M; Drögemüller M; Garrick DCerebellar hypoplasia is a heterogeneous neurological condition in which the cerebellum is smaller than usual or not completely developed. The condition can have genetic origins, with Mendelian-effect mutations described in several mammalian species. Here, we describe a genetic investigation of cerebellar hypoplasia in White Swiss Shepherd dogs, where two affected puppies were identified from a litter with a recent common ancestor on both sides of their pedigree. Whole genome sequencing was conducted for 10 dogs in this family, and filtering of these data based on a recessive transmission hypothesis highlighted five protein-altering candidate variants - including a frameshift-deletion of the Reelin (RELN) gene (p.Val947*). Given the status of RELN as a gene responsible for cerebellar hypoplasia in humans, sheep and mice, these data strongly suggest the loss-of-function variant as underlying these effects. This variant has not been found in other dog breeds nor in a cohort of European White Swiss Shepherds, suggesting a recent mutation event. This finding will support the genotyping of a more diverse sample of dogs, and should aid future management of the harmful allele through optimised mating schemes.Item Genomic Insights Into Clinical Shiga Toxin-Producing Escherichia coli Strains: A 15-Year Period Survey in Jönköping, Sweden(Frontiers Media S.A., 2021-02-05) Bai X; Zhang J; Hua Y; Jernberg C; Xiong Y; French N; Löfgren S; Hedenström I; Ambikan A; Mernelius S; Matussek A; González-Escalona NShiga toxin-producing Escherichia coli (STEC) are important foodborne pathogens that can cause human infections ranging from asymptomatic carriage to bloody diarrhea (BD) and fatal hemolytic uremic syndrome (HUS). However, the molecular mechanism of STEC pathogenesis is not entirely known. Here, we demonstrated a large scale of molecular epidemiology and in-depth genomic study of clinical STEC isolates utilizing clinical and epidemiological data collected in Region Jönköping County, Sweden, over a 15-year period. Out of 184 STEC isolates recovered from distinct patients, 55 were from patients with BD, and 129 were from individuals with non-bloody stools (NBS). Five individuals developed HUS. Adults were more associated with BD. Serotypes O157:H7, O26:H11, O103:H2, O121:H19, and O104:H4 were more often associated with BD. The presence of Shiga toxin-encoding gene subtypes stx 2a, stx 2a + stx 2c, and stx 1a + stx 2c was associated with BD, while stx 1 a was associated with milder disease. Multiplex virulence and accessory genes were correlated with BD; these genes encode toxins, adhesion, autotransporters, invasion, and secretion system. A number of antimicrobial resistance (AMR) genes, such as aminoglycoside, aminocoumarin, macrolide, and fluoroquinolone resistance genes, were prevalent among clinical STEC isolates. Whole-genome phylogeny revealed that O157 and non-O157 STEC isolates evolved from distinct lineages with a few exceptions. Isolates from BD showed more tendency to cluster closely. In conclusion, this study unravels molecular trait of clinical STEC strains and identifies genetic factors associated with severe clinical outcomes, which could contribute to management of STEC infections and disease progression if confirmed by further functional validation.Item A Deletion in GDF7 is Associated with a Heritable Forebrain Commissural Malformation Concurrent with Ventriculomegaly and Interhemispheric Cysts in Cats(MDPI (Basel, Switzerland), 2020-06-19) Yu Y; Creighton EK; Buckley RM; Lyons LA; 99 Lives ConsortiumAn inherited neurologic syndrome in a family of mixed-breed Oriental cats has been characterized as forebrain commissural malformation, concurrent with ventriculomegaly and interhemispheric cysts. However, the genetic basis for this autosomal recessive syndrome in cats is unknown. Forty-three cats were genotyped on the Illumina Infinium Feline 63K iSelect DNA Array and used for analyses. Genome-wide association studies, including a sib-transmission disequilibrium test and a case-control association analysis, and homozygosity mapping, identified a critical region on cat chromosome A3. Short-read whole genome sequencing was completed for a cat trio segregating with the syndrome. A homozygous 7 bp deletion in growth differentiation factor 7 (GDF7) (c.221_227delGCCGCGC [p.Arg74Profs]) was identified in affected cats, by comparison to the 99 Lives Cat variant dataset, validated using Sanger sequencing and genotyped by fragment analyses. This variant was not identified in 192 unaffected cats in the 99 Lives dataset. The variant segregated concordantly in an extended pedigree. In mice, GDF7 mRNA is expressed within the roof plate when commissural axons initiate ventrally-directed growth. This finding emphasized the importance of GDF7 in the neurodevelopmental process in the mammalian brain. A genetic test can be developed for use by cat breeders to eradicate this variant.Item Comparative Genomics of Mycobacterium avium Subspecies Paratuberculosis Sheep Strains(Frontiers Media S.A., 2021-02-15) Mizzi R; Timms VJ; Price-Carter ML; Gautam M; Whittington R; Heuer C; Biggs PJ; Plain KM; Salgado MMycobacterium avium subspecies paratuberculosis (MAP) is the aetiological agent of Johne's disease (JD), a chronic enteritis that causes major losses to the global livestock industry. Further, it has been associated with human Crohn's disease. Several strains of MAP have been identified, the two major groups being sheep strain MAP, which includes the Type I and Type III sub-lineages, and the cattle strain or Type II MAP lineage, of which bison strains are a sub-grouping. Major genotypic, phenotypic and pathogenic variations have been identified in prior comparisons, but the research has predominately focused on cattle strains of MAP. In countries where the sheep industries are more prevalent, however, such as Australia and New Zealand, ovine JD is a substantial burden. An information gap exists regarding the genomic differences between sheep strain sub-lineages and the relevance of Type I and Type III MAP in terms of epidemiology and/or pathogenicity. We therefore investigated sheep MAP isolates from Australia and New Zealand using whole genome sequencing. For additional context, sheep MAP genome datasets were downloaded from the Sequence Read Archive and GenBank. The final dataset contained 18 Type III and 16 Type I isolates and the K10 cattle strain MAP reference genome. Using a pan-genome approach, an updated global phylogeny for sheep MAP from de novo assemblies was produced. When rooted with the K10 cattle reference strain, two distinct clades representing the lineages were apparent. The Australian and New Zealand isolates formed a distinct sub-clade within the type I lineage, while the European type I isolates formed another less closely related group. Within the type III lineage, isolates appeared more genetically diverse and were from a greater number of continents. Querying of the pan-genome and verification using BLAST analysis revealed lineage-specific variations (n = 13) including genes responsible for metabolism and stress responses. The genetic differences identified may represent important epidemiological and virulence traits specific to sheep MAP. This knowledge will potentially contribute to improved vaccine development and control measures for these strains.