Publications by year
In Press
Weedon MN, Jackson L, Harrison JW, Ruth KS, Tyrrell J, Hattersley AT, Wright CF (In Press). Assessing the analytical validity of SNP-chips for detecting very rare pathogenic variants: implications for direct-to-consumer genetic testing.
Abstract:
Assessing the analytical validity of SNP-chips for detecting very rare pathogenic variants: implications for direct-to-consumer genetic testing
ABSTRACTObjectivesTo determine the analytical validity of SNP-chips for genotyping very rare genetic variants.DesignRetrospective study using data from two publicly available resources, the UK Biobank and the Personal Genome Project.SettingResearch biobanks and direct-to-consumer genetic testing in the UK and USA.Participants49,908 individuals recruited to UK Biobank, and 21 individuals who purchased consumer genetic tests and shared their data online via the Personal Genomes Project.Main outcome measuresWe assessed the analytical validity of genotypes from SNP-chips (index test) with sequencing data (reference standard). We evaluated the genotyping accuracy of the SNP-chips and split the results by variant frequency. We went on to select rare pathogenic variants in the BRCA1 and BRCA2 genes as an exemplar for detailed analysis of clinically-actionable variants in UK Biobank, and assessed BRCA-related cancers (breast, ovarian, prostate and pancreatic) in participants using cancer registry data.ResultsSNP-chip genotype accuracy is high overall; sensitivity, specificity and precision are all >99% for 108,574 common variants directly genotyped by the UK Biobank SNP-chips. However, the likelihood of a true positive result reduces dramatically with decreasing variant frequency; for variants with a frequency <0.001% in UK Biobank the precision is very low and only 16% of 4,711 variants from the SNP-chips confirm with sequencing data. Results are similar for SNP-chip data from the Personal Genomes Project, and 20/21 individuals have at least one rare pathogenic variant that has been incorrectly genotyped. For pathogenic variants in the BRCA1 and BRCA2 genes, the overall performance metrics of the SNP-chips in UK Biobank are sensitivity 34.6%, specificity 98.3% and precision 4.2%. Rates of BRCA-related cancers in individuals in UK Biobank with a positive SNP-chip result are similar to age-matched controls (OR 1.28, P=0.07, 95% CI: 0.98 to 1.67), while sequence-positive individuals have a significantly increased risk (OR 3.73, P=3.5×10−12, 95% CI: 2.57 to 5.40).ConclusionSNP-chips are extremely unreliable for genotyping very rare pathogenic variants and should not be used to guide health decisions without validation.SUMMARY BOXSection 1: What is already known on this topicSNP-chips are an accurate and affordable method for genotyping common genetic variants across the genome. They are often used by direct-to-consumer (DTC) genetic testing companies and research studies, but there several case reports suggesting they perform poorly for genotyping rare genetic variants when compared with sequencing.Section 2: What this study addsOur study confirms that SNP-chips are highly inaccurate for genotyping rare, clinically-actionable variants. Using large-scale SNP-chip and sequencing data from UK Biobank, we show that SNP-chips have a very low precision of <16% for detecting very rare variants (i.e. the majority of variants with population frequency of <0.001% are false positives). We observed a similar performance in a small sample of raw SNP-chip data from DTC genetic tests. Very rare variants assayed using SNP-chips should not be used to guide health decisions without validation.
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Oram RA, Weedon M, Wood A, Beaumont R, Tyrrell J (In Press). Development and Standardization of an Improved Type 1 Diabetes Genetic Risk Score for Use in Newborn Screening and Incident
Diagnosis.
Diabetes Care Full text.
Jones SE, van Hees VT, Mazzotti DR, Marques-Vidal P, Sabia S, van der Spek A, Dashti HS, Engmann J, Kocevska D, Tyrrell J, et al (In Press). Genetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour.
Nature CommunicationsAbstract:
Genetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour
Sleep is an essential human function but its regulation is poorly understood. Using accelerometer data from 85,670 UK Biobank participants, we perform a genome-wide association study of 8 derived sleep traits representing sleep quality, quantity and timing, and validate our findings in 5,819 individuals. We identify 47 genetic associations at P
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Masoli JAH, Jeffries A, Temperton B, Auckland C, Michelsen M, Warwick-Dugdale J, Manley R, Farbos A, Ellard S, Knight B, et al (In Press). Viral genetic sequencing identifies staff transmission of COVID-19 is important in a community hospital outbreak.
Abstract:
Viral genetic sequencing identifies staff transmission of COVID-19 is important in a community hospital outbreak
AbstractBackgroundWe have successfully used whole-genome sequencing to provide additional information for transmission pathways in infectious spread. We report and interpret genomic sequencing results in clinical context from a large outbreak of COVID-19 with 46 cases across staff and patients in a community hospital in the UK.MethodsFollowing multiple symptomatic cases within a two-week period, all staff and patients were screened by RT-PCR and staff subsequently had serology tests.ResultsThirty staff (25%) and 16 patients (62%) tested positive for COVID-19. Genomic sequencing data showed significant overlap of viral haplotypes in staff who had overlapping shift patterns. Patient haplotypes were more distinct from each other but had overlap with staff haplotypes.ConclusionsThis study includes clinical and genomic epidemiological detail that demonstrates the value of a combined approach. Viral genetic sequencing has identified that staff transmission of COVID-19 was important in this community hospital outbreak.Key pointsDetailed analysis of a large community hospital outbreak in older adults and staff with concurrent clinical and genomic data, including working patterns.Staff transmission was important in this community hospital outbreak.We found plausible associations between staff and patient cases.
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2020
Sambles C, Venkatesan L, Shittu OM, Harrison J, Moore K, Tripathi L, Grant M, Warmington R, Studholme DJ (2020). Genome sequencing data for wild and cultivated bananas, plantains and abacá.
Data in Brief,
33Abstract:
Genome sequencing data for wild and cultivated bananas, plantains and abacá
We performed shotgun genome sequencing on a total of 19 different Musa genotypes including representatives of wild banana species Musa acuminata and M. balibisiana, allopolyploid bananas and plantains, Fe'i banana, pink banana (also known as hairy banana) and abacá (also known as hemp banana). We aligned sequence reads against a previously sequenced reference genome and assessed ploidy and, in the case of allopolyploids, the contributions of the a and B genomes; this provides important quality-assurance data about the taxonomic identities of the sequenced plant material. These data will be useful for phylogenetics, crop improvement, studies of the complex story of intergenomic recombination in AAB and ABB allotriploid bananas and plantains and can be integrated into resources such as the Banana Genome Hub.
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Fasham J, Leslie JS, Harrison JW, Deline J, Williams KB, Kuhl A, Scott Schwoerer J, Cross HE, Crosby AH, Baple EL, et al (2020). No association between SCN9A and monogenic human epilepsy disorders.
PLOS Genetics,
16(11), e1009161-e1009161.
Abstract:
No association between SCN9A and monogenic human epilepsy disorders
Many studies have demonstrated the clinical utility and importance of epilepsy gene panel testing to confirm the specific aetiology of disease, enable appropriate therapeutic interventions, and inform accurate family counselling. Previously, SCN9A gene variants, in particular a c.1921A>T p.(Asn641Tyr) substitution, have been identified as a likely autosomal dominant cause of febrile seizures/febrile seizures plus and other monogenic seizure phenotypes indistinguishable from those associated with SCN1A, leading to inclusion of SCN9A on epilepsy gene testing panels. Here we present serendipitous findings of genetic studies that identify the SCN9A c.1921A>T p.(Asn641Tyr) variant at high frequency in the Amish community in the absence of such seizure phenotypes. Together with findings in UK Biobank these data refute an association of SCN9A with epilepsy, which has important clinical diagnostic implications.
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Harrison JW, Tallapragada DSP, Baptist A, Sharp SA, Bhaskar S, Jog KS, Patel KA, Weedon MN, Chandak GR, Yajnik CS, et al (2020). Type 1 diabetes genetic risk score is discriminative of diabetes in non-Europeans: evidence from a study in India.
Scientific Reports,
10(1).
Abstract:
Type 1 diabetes genetic risk score is discriminative of diabetes in non-Europeans: evidence from a study in India
AbstractType 1 diabetes (T1D) is a significant problem in Indians and misclassification of T1D and type 2 diabetes (T2D) is a particular problem in young adults in this population due to the high prevalence of early onset T2D at lower BMI. We have previously shown a genetic risk score (GRS) can be used to discriminate T1D from T2D in Europeans. We aimed to test the ability of a T1D GRS to discriminate T1D from T2D and controls in Indians. We studied subjects from Pune, India of Indo-European ancestry; T1D (n = 262 clinically defined, 200 autoantibody positive), T2D (n = 345) and controls (n = 324). We used the 9 SNP T1D GRS generated in Europeans and assessed its ability to discriminate T1D from T2D and controls in Indians. We compared Indians with Europeans from the Wellcome Trust Case Control Consortium study; T1D (n = 1963), T2D (n = 1924) and controls (n = 2938). The T1D GRS was discriminative of T1D from T2D in Indians but slightly less than in Europeans (ROC AUC 0.84 v 0.87, p < 0.0001). HLA SNPs contributed the majority of the discriminative power in Indians. A T1D GRS using SNPs defined in Europeans is discriminative of T1D from T2D and controls in Indians. As with Europeans, the T1D GRS may be useful for classifying diabetes in Indians.
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Harrison J (2020). Use of Next Generation Sequencing to Investigate the Genomics of Bacterial Pathogens.
Abstract:
Use of Next Generation Sequencing to Investigate the Genomics of Bacterial Pathogens.
This thesis explores the use of next generation sequencing as a tool to investigate the genomics of bacterial pathogens of plants and humans.
Firstly, second-generation sequencing was applied to the evolution of distantly related bacterial species that have converged on common host plants (Xanthomonas bacteria on sugarcane and common-bean plants). This revealed evidence of recent horizontal gene transfer between X. phaseoli pv. phaseoli and X. citri pv. fuscans and between X. axonopodis pv. vasculorum and X. vasicola. distantly related sugarcane pathogens. Furthermore, we discovered that strains isolated from lablab bean (a close relative of common bean) form a previously unknown third distinct clade (and perhaps pathovar) and whole-genome comparisons suggested horizontal gene transfer played an important role in the evolution of host specificity in xanthomonad pathogens.
Next, second-generation sequencing was used to rapidly gain insight into novel emerging bacterial pathogens, namely unusually virulent Asian strains of the human pathogen Campylobacter jejuni and a xanthomonad causing unusual symptoms on common bean in African country of Rwanda. A type six secretion system was shown to be associated with a more serious form of campylobacteriosis and a molecular marker for an intact type six secretion system was identified. This was shown to be more prevalent in strains isolated from Asia than strains isolated in the UK, a finding which has serious implications for chicken import. Further to this the genome sequence of a newly emerging Xanthomonas bean pathogen isolated from a recent outbreak in Rwanda is presented. Analysis of the Rwandan Xanthomonas genome shows it represents the first sequenced isolate in a novel species level clade, which was subsequently named as Xanthomonas cannabis and is genetically distinct from previously known bean pathogens.
Lastly, the performance of the third-generation sequencing platform Oxford Nanopore MinION was assessed which will prove to be an exciting resource to perform bacterial genomic studies in the future. In summary, this work exemplifies the value of sequencing-based approaches for rapidly and cheaply gaining insights into evolution of bacterial pathogens
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2019
Bewshea CM, Ahmad T, Kennedy N, Weedon M, Harrison J, Walker G, Goodhand J, Jones S (2019). Association of Genetic Variants in NUDT15 with Thiopurine-Induced
Myelosuppression in Patients with Inflammatory Bowel Disease.
JAMA - Journal of the American Medical Association,
321 (8), 773-785.
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Bovijn J, Jackson L, Censin J, Chen CY, Laisk T, Laber S, Ferreira T, Pulit SL, Glastonbury CA, Smoller JW, et al (2019). GWAS Identifies Risk Locus for Erectile Dysfunction and Implicates Hypothalamic Neurobiology and Diabetes in Etiology.
American Journal of Human Genetics,
104(1), 157-163.
Abstract:
GWAS Identifies Risk Locus for Erectile Dysfunction and Implicates Hypothalamic Neurobiology and Diabetes in Etiology
Erectile dysfunction (ED) is a common condition affecting more than 20% of men over 60 years, yet little is known about its genetic architecture. We performed a genome-wide association study of ED in 6,175 case subjects among 223,805 European men and identified one locus at 6q16.3 (lead variant rs57989773, OR 1.20 per C-allele; p = 5.71 × 10−14), located between MCHR2 and SIM1. In silico analysis suggests SIM1 to confer ED risk through hypothalamic dysregulation. Mendelian randomization provides evidence that genetic risk of type 2 diabetes mellitus is a cause of ED (OR 1.11 per 1-log unit higher risk of type 2 diabetes). These findings provide insights into the biological underpinnings and the causes of ED and may help prioritize the development of future therapies for this common disorder.
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Jones SE, Lane JM, Wood AR, van Hees VT, Tyrrell J, Beaumont RN, Jeffries AR, Dashti HS, Hillsdon M, Ruth KS, et al (2019). Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms.
Nature CommunicationsAbstract:
Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms
Using genome-wide data from 697,828 UK Biobank and 23andMe participants, we increase the number of identified loci associated with being a morning person, a behavioural indicator of a person’s underlying circadian rhythm, from 24 to 351. Using data from 85,760 individuals with activity-monitor derived measures of sleep timing we demonstrate that the chronotype loci influence sleep timing: the mean sleep timing of the 5% of individuals carrying the most morningness alleles is 25 minutes earlier than the 5% carrying the fewest. The loci are enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. Using Mendelian Randomisation, we show that being a morning person is causally associated with better mental health but does not affect BMI or risk of Type 2 diabetes. This study offers insights into circadian biology and its links to disease in humans.
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Schafmayer C, Harrison JW, Buch S, Lange C, Reichert MC, Hofer P, Cossais F, Kupcinskas J, von Schönfels W, Schniewind B, et al (2019). Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms.
Gut,
68(5), 854-865.
Abstract:
Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms.
OBJECTIVE: Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. DESIGN: Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. RESULTS: We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p
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Tyrrell J, Mulugeta A, Wood AR, Zhou A, Beaumont RN, Tuke MA, Jones SE, Ruth KS, Yaghootkar H, Sharp S, et al (2019). Using genetics to understand the causal influence of higher BMI on depression.
Int J Epidemiol,
48(3), 834-848.
Abstract:
Using genetics to understand the causal influence of higher BMI on depression.
BACKGROUND: Depression is more common in obese than non-obese individuals, especially in women, but the causal relationship between obesity and depression is complex and uncertain. Previous studies have used genetic variants associated with BMI to provide evidence that higher body mass index (BMI) causes depression, but have not tested whether this relationship is driven by the metabolic consequences of BMI nor for differences between men and women. METHODS: We performed a Mendelian randomization study using 48 791 individuals with depression and 291 995 controls in the UK Biobank, to test for causal effects of higher BMI on depression (defined using self-report and Hospital Episode data). We used two genetic instruments, both representing higher BMI, but one with and one without its adverse metabolic consequences, in an attempt to 'uncouple' the psychological component of obesity from the metabolic consequences. We further tested causal relationships in men and women separately, and using subsets of BMI variants from known physiological pathways. RESULTS: Higher BMI was strongly associated with higher odds of depression, especially in women. Mendelian randomization provided evidence that higher BMI partly causes depression. Using a 73-variant BMI genetic risk score, a genetically determined one standard deviation (1 SD) higher BMI (4.9 kg/m2) was associated with higher odds of depression in all individuals [odds ratio (OR): 1.18, 95% confidence interval (CI): 1.09, 1.28, P = 0.00007) and women only (OR: 1.24, 95% CI: 1.11, 1.39, P = 0.0001). Meta-analysis with 45 591 depression cases and 97 647 controls from the Psychiatric Genomics Consortium (PGC) strengthened the statistical confidence of the findings in all individuals. Similar effect size estimates were obtained using different Mendelian randomization methods, although not all reached P
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2018
Frayling TM (2018). A Common Allele in FGF21 Associated with Sugar Intake is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure.
Cell Reports,
23(2), 327-336.
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Wagley S, Borne R, Harrison J, Baker-Austin C, Ottaviani D, Leoni F, Vuddhakul V, Titball RW (2018). Galleria mellonella as an infection model to investigate virulence of Vibrio parahaemolyticus.
Virulence,
9(1), 197-207.
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Galleria mellonella as an infection model to investigate virulence of Vibrio parahaemolyticus.
Non-toxigenic V. parahaemolyticus isolates (tdh-/trh-/T3SS2-) have recently been isolated from patients with gastroenteritis. In this study we report that the larvae of the wax moth (Galleria mellonella) are susceptible to infection by toxigenic or non-toxigenic clinical isolates of V. parahaemolyticus. In comparison larvae inoculated with environmental isolates of V. parahaemolyticus did not succumb to disease. Whole genome sequencing of clinical non-toxigenic isolates revealed the presence of a gene encoding a nudix hydrolase, identified as mutT. A V. parahaemolyticus mutT mutant was unable to kill G. mellonella at 24 h post inoculation, indicating a role of this gene in virulence. Our findings show that G. mellonella is a valuable model for investigating screening of possible virulence genes of V. parahaemolyticus and can provide new insights into mechanisms of virulence of atypical non-toxigenic V. parahaemolyticus. These findings will allow improved genetic tests for the identification of pathogenic V. parahaemolyticus to be developed and will have a significant impact for the scientific community.
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Walker GJ, Harrison JW, Voskuil MD, Heap GA, Heerasing N, Hendy PJ, Koskela J, Daly MJ, Sokol H, Weersma RK, et al (2018). NUDT15 VARIANTS CONTRIBUTE TO THIOPURINE-INDUCED MYELOSUPPRESSION IN EUROPEAN POPULATIONS.
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2017
Walker GJ, Harrison JW, Heap GA, Heerasing N, Hendy PJ, Bewshea C, Goodhand JR, Weedon MN, Kennedy NA, Ahmad T, et al (2017). NUDT15 VARIANTS CONTRIBUTE TO THIOPURINE-INDUCED MYELOSUPPRESSION IN EUROPEAN POPULATIONS.
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2016
Harrison J, Dornbusch MR, Samac D, Studholme DJ (2016). Draft Genome Sequence of Pseudomonas syringae pv. syringae ALF3 Isolated from Alfalfa.
Genome Announc,
4(1).
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Draft Genome Sequence of Pseudomonas syringae pv. syringae ALF3 Isolated from Alfalfa.
We report here the annotated draft genome sequence of Pseudomonas syringae pv. syringae strain ALF3, isolated in Wyoming. A comparison of this genome sequence with those of closely related strains of P. syringae adapted to other hosts will facilitate research into interactions between this pathogen and alfalfa.
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Harrison J, Grant MR, Studholme DJ (2016). Draft Genome Sequences of Two Strains of Xanthomonas arboricola pv. celebensis Isolated from Banana Plants.
Genome Announc,
4(1).
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Draft Genome Sequences of Two Strains of Xanthomonas arboricola pv. celebensis Isolated from Banana Plants.
We report here the annotated draft genome sequences of strains Xanthomonas arboricola pv. celebensis NCPPB 1832 and NCPPB 1630 (NCPPB, National Collection of Plant Pathogenic Bacteria), both isolated from Musa species in New Zealand. This will allow the comparison of genomes between phylogenetically distant xanthomonads that have independently converged with the ability to colonize banana plants.
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McDonagh LM, West H, Harrison JW, Stevens JR (2016). Which mitochondrial gene (if any) is best for insect phylogenetics?.
INSECT SYSTEMATICS & EVOLUTION,
47(3), 245-266.
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2015
Laver T, Harrison J, O'Neill PA, Moore K, Farbos A, Paszkiewicz K, Studholme DJ (2015). Assessing the performance of the Oxford Nanopore Technologies MinION.
Biomolecular Detection and Quantification,
3, 1-8.
Abstract:
Assessing the performance of the Oxford Nanopore Technologies MinION
The Oxford Nanopore Technologies (ONT) MinION is a new sequencing technology that potentially offers read lengths of tens of kilobases (kb) limited only by the length of DNA molecules presented to it. The device has a low capital cost, is by far the most portable DNA sequencer available, and can produce data in real-time. It has numerous prospective applications including improving genome sequence assemblies and resolution of repeat-rich regions. Before such a technology is widely adopted, it is important to assess its performance and limitations in respect of throughput and accuracy. In this study we assessed the performance of the MinION by re-sequencing three bacterial genomes, with very different nucleotide compositions ranging from 28.6% to 70.7%; the high G. +. C strain was underrepresented in the sequencing reads. We estimate the error rate of the MinION (after base calling) to be 38.2%. Mean and median read lengths were 2. kb and 1. kb respectively, while the longest single read was 98. kb. The whole length of a 5. kb rRNA operon was covered by a single read. As the first nanopore-based single molecule sequencer available to researchers, the MinION is an exciting prospect; however, the current error rate limits its ability to compete with existing sequencing technologies, though we do show that MinION sequence reads can enhance contiguity of de novo assembly when used in conjunction with Illumina MiSeq data.
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Aritua V, Harrison J, Sapp M, Buruchara R, Smith J, Studholme DJ (2015). Genome sequencing reveals a new lineage associated with lablab bean and genetic exchange between Xanthomonas axonopodis pv. phaseoli and Xanthomonas fuscans subsp. fuscans.
Front Microbiol,
6Abstract:
Genome sequencing reveals a new lineage associated with lablab bean and genetic exchange between Xanthomonas axonopodis pv. phaseoli and Xanthomonas fuscans subsp. fuscans.
Common bacterial blight is a devastating seed-borne disease of common beans that also occurs on other legume species including lablab and Lima beans. We sequenced and analyzed the genomes of 26 strains of Xanthomonas axonopodis pv. phaseoli and X. fuscans subsp. fuscans, the causative agents of this disease, collected over four decades and six continents. This revealed considerable genetic variation within both taxa, encompassing both single-nucleotide variants and differences in gene content, that could be exploited for tracking pathogen spread. The bacterial strain from Lima bean fell within the previously described Genetic Lineage 1, along with the pathovar type strain (NCPPB 3035). The strains from lablab represent a new, previously unknown genetic lineage closely related to strains of X. axonopodis pv. glycines. Finally, we identified more than 100 genes that appear to have been recently acquired by Xanthomonas axonopodis pv. phaseoli from X. fuscans subsp. fuscans.
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Aritua V, Musoni A, Kabeja A, Butare L, Mukamuhirwa F, Gahakwa D, Kato F, Abang MM, Buruchara R, Sapp M, et al (2015). The draft genome sequence of Xanthomonas species strain Nyagatare, isolated from diseased bean in Rwanda.
FEMS Microbiol Lett,
362(4).
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The draft genome sequence of Xanthomonas species strain Nyagatare, isolated from diseased bean in Rwanda.
We announce the genome sequence for Xanthomonas species strain Nyagatare, isolated from beans showing unusual disease symptoms in Rwanda. This strain represents the first sequenced genome belonging to an as-yet undescribed Xanthomonas species known as species-level clade 1. It has at least 100 kb of genomic sequence that shows little or no sequence similarity to other xanthomonads, including a unique lipopolysaccharide synthesis gene cluster. At least one genomic region appears to have been acquired from relatives of Agrobacterium or Rhizobium species. The genome encodes homologues of only three known type-three secretion system effectors: AvrBs2, XopF1 and AvrXv4. Availability of the genome sequence will facilitate development of molecular tools for detection and diagnostics for this newly discovered pathogen of beans and facilitate epidemiological investigations of a potential causal link between this pathogen and the disease outbreak.
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2014
Harrison J, Moore K, Paszkiewicz K, Jones T, Grant M, Ambacheew D, Muzemil S, Studholme D (2014). A Draft Genome Sequence for Ensete ventricosum, the Drought-Tolerant “Tree Against Hunger”.
Agronomy,
4, 13-33.
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A Draft Genome Sequence for Ensete ventricosum, the Drought-Tolerant “Tree Against Hunger”
We present a draft genome sequence for enset (Ensete ventricosum) available via the Sequence Read Archive (accession number SRX202265) and GenBank (accession number AMZH01. Enset feeds 15 million people in Ethiopia, but is arguably the least studied African crop. Our sequence data suggest a genome size of approximately 547 megabases, similar to the 523-megabase genome of the closely related banana (Musa acuminata). At least 1.8% of the annotated M. acuminata genes are not conserved in E. ventricosum. Furthermore, enset contains genes not present in banana, including reverse transcriptases and virus-like sequences as well as a homolog of the RPP8-like resistance gene. We hope that availability of genome-wide sequence data will stimulate and accelerate research on this important but neglected crop.
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Harrison J, Studholme DJ (2014). Draft genome sequence of Xanthomonas axonopodis pathovar vasculorum NCPPB 900.
FEMS Microbiology Letters,
360(2), 113-116.
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Draft genome sequence of Xanthomonas axonopodis pathovar vasculorum NCPPB 900
Xanthomonas axonopodis pathovar vasculorum strain NCPPB 900 was isolated from sugarcane on Reunion island in 1960. Consistent with its belonging to fatty-acid type D, multi-locus sequence analysis confirmed that NCPPB 900 falls within the species X. axonopodis. This genome harbours sequences similar to plasmids pXCV183 from X. campestris pv. vesicatoria 85-10 and pPHB194 from Burkholderia pseudomallei. Its repertoire of predicted effectors includes homologues of XopAA, XopAD, XopAE, XopB, XopD, XopV, XopZ, XopC and XopI and transcriptional activator-like effectors and it is predicted to encode a novel phosphonate natural product also encoded by the genome of the phylogenetically distant X. vasicola pv. vasculorum. Availability of this novel genome sequence may facilitate the study of interactions between xanthomonads and sugarcane, a host-pathogen system that appears to have evolved several times independently within the genus Xanthomonas and may also provide a source of target sequences for molecular detection and diagnostics. We present the genome sequence of a bacterial agent of gumming disease of sugarcane.
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Harrison JW, Dung TTN, Siddiqui F, Korbrisate S, Bukhari H, Tra MPV, Hoang NVM, Carrique-Mas J, Bryant J, Campbell JI, et al (2014). Identification of possible virulence marker from Campylobacter jejuni isolates.
Emerg Infect Dis,
20(6), 1026-1029.
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Identification of possible virulence marker from Campylobacter jejuni isolates.
A novel protein translocation system, the type-6 secretion system (T6SS), may play a role in virulence of Campylobacter jejuni. We investigated 181 C. jejuni isolates from humans, chickens, and environmental sources in Vietnam, Thailand, Pakistan, and the United Kingdom for T6SS. The marker was most prevalent in human and chicken isolates from Vietnam.
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Harrison J, Studholme DJ (2014). Recently published Streptomyces genome sequences.
Microb Biotechnol,
7(5), 373-380.
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2013
Quinn L, O'Neill PA, Harrison J, Paskiewicz KH, Mccracken AR, Cooke LR, Grant MR, Studholme DJ (2013). Genome-wide sequencing of Phytophthora lateralis reveals genetic variation among isolates from Lawson cypress (Chamaecyparis lawsoniana) in Northern Ireland.
FEMS Microbiology Letters,
344(2), 179-185.
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Genome-wide sequencing of Phytophthora lateralis reveals genetic variation among isolates from Lawson cypress (Chamaecyparis lawsoniana) in Northern Ireland
Phytophthora lateralis is a fungus-like (oomycete) pathogen of trees in the family Cupressaceae, including Chamaecyparis lawsoniana (Lawson cypress or Port Orford cedar). Known in North America since the 1920s, presumably having been accidentally introduced from its assumed East Asian centre of origin, until recently, this pathogen has not been identified causing disease in Europe except for a few isolated outbreaks. However, since 2010, there have been several reports of infection of C. lawsoniana by P. lateralis in the United Kingdom, including Northern Ireland. We sequenced the genomes of four isolates of P. lateralis from two sites in Northern Ireland in 2011. Comparison with the closely related tree and shrub pathogen P. ramorum (cause of ramorum disease of larch and other species in the UK) shows that P. lateralis shares 91.47% nucleotide sequence identity over the core conserved compartments of the genome. The genomes of the four Northern Ireland isolates are almost identical, but we identified several single-nucleotide polymorphisms (SNPs) that distinguish between isolates, thereby presenting potential molecular markers of use for tracking routes of spread and in epidemiological studies. Our data reveal very low rates of heterozygosity (compared with P. ramorum), consistent with inbreeding within this P. lateralis population. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd.
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Quinn L, O'Neill PA, Harrison J, Paskiewicz KH, McCracken AR, Cooke LR, Grant MR, Studholme DJ (2013). Genome-wide sequencing of Phytophthora lateralis reveals genetic variation among isolates from Lawson cypress (Chamaecyparis lawsoniana) in Northern Ireland.
FEMS Microbiol Lett,
344(2), 179-185.
Abstract:
Genome-wide sequencing of Phytophthora lateralis reveals genetic variation among isolates from Lawson cypress (Chamaecyparis lawsoniana) in Northern Ireland.
Phytophthora lateralis is a fungus-like (oomycete) pathogen of trees in the family Cupressaceae, including Chamaecyparis lawsoniana (Lawson cypress or Port Orford cedar). Known in North America since the 1920s, presumably having been accidentally introduced from its assumed East Asian centre of origin, until recently, this pathogen has not been identified causing disease in Europe except for a few isolated outbreaks. However, since 2010, there have been several reports of infection of C. lawsoniana by P. lateralis in the United Kingdom, including Northern Ireland. We sequenced the genomes of four isolates of P. lateralis from two sites in Northern Ireland in 2011. Comparison with the closely related tree and shrub pathogen P. ramorum (cause of ramorum disease of larch and other species in the UK) shows that P. lateralis shares 91.47% nucleotide sequence identity over the core conserved compartments of the genome. The genomes of the four Northern Ireland isolates are almost identical, but we identified several single-nucleotide polymorphisms (SNPs) that distinguish between isolates, thereby presenting potential molecular markers of use for tracking routes of spread and in epidemiological studies. Our data reveal very low rates of heterozygosity (compared with P. ramorum), consistent with inbreeding within this P. lateralis population.
Abstract.
Author URL.
2011
Kim E, Harrison JW, Sudek S, Jones MDM, Wilcox HM, Richards TA, Worden AZ, Archibald JM (2011). Newly identified and diverse plastid-bearing branch on the eukaryotic tree of life.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
108(4), 1496-1500.
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