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September 2015 - present
January 2013 - present
Education
October 2007 - June 2011
September 1997 - July 2001
Publications
Publications (80)
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Human African trypanosomiasis is caused by two subspecies of Trypanosoma brucei. Trypanosoma brucei rhodesiense is found in East Africa and frequently causes acute disease, while Trypanosoma brucei gambiense is found in West Africa and is associated with chronic disease. Samples taken from a single focus of a Ugandan outbreak of T. b....
Recent data from several organisms indicate that the transcribed portions of genomes are larger and more complex than expected, and that many functional properties of transcripts are based not on coding sequences but on regulatory sequences in untranslated regions or non-coding RNAs. Alternative start and polyadenylation sites and regulation of int...
African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including approximately 900 pseudogenes and approximately 1700 T. brucei-specific genes. Large...
Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We...
Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 mill...
The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats the...
Interactions between hosts and their resident microbial communities are a fundamental component of fitness for both agents. Though recent research has highlighted the importance of interactions between animals and their bacterial communities, comparative evidence for fungi is lacking, especially in natural populations. Using data from 49 species, w...
Interactions between hosts and their resident microbial communities are a fundamental component of fitness for both agents. Though recent research has highlighted the importance of interactions between animals and their bacterial communities, comparative evidence for fungi is lacking, especially in natural populations. Using data from 49 species, w...
The majority of bacterial genomes have high coding efficiencies, but there are some genomes of intracellular bacteria that have low gene density. The genome of the endosymbiont Sodalis glossinidius contains almost 50 % pseudogenes containing mutations that putatively silence them at the genomic level. We have applied multiple 'omic' strategies, com...
Tree pathogens are a major threat to forest ecosystems. Conservation management strategies can exploit natural mechanisms of resistance, such as tree genotype and host‐associated microbial communities. However, fungal and bacterial communities are rarely looked at in the same framework, particularly in conjunction with host genotype. Here, we explo...
Profiling of wild and laboratory tsetse populations using 16S rRNA gene amplicon sequencing allowed us to examine whether the “Wigglesworthia-Sodalis-Wolbachia dogma” operates across species and populations. The most abundant taxa, in wild and laboratory populations, were Wigglesworthia (the primary endosymbiont), Sodalis and Wolbachia as previousl...
Microbial ecology provides insights into the ecological and evolutionary dynamics of microbial
communities underpinning every ecosystem on Earth. Microbial communities can now be investigated
in unprecedented detail, although there is still a wealth of open questions to be tackled. Here we
identify 50 research questions of fundamental importance to...
Almost all genome sequencing projects neglect the fact that diploid organisms contain two genome copies and consequently what is published is a composite of the two. This means that the relationship between alternate alleles at two or more linked loci is lost. We have developed a simplified method of directly obtaining the haploid sequences of each...
Differentiation of one life-cycle stage to the next is critical for survival and transmission of apicomplexan parasites. A number of studies have shown that stage differentiation is a stochastic process and is associated with a point that commits the cell to a change over in the pattern of gene expression. Studies on differentiation to merozoite pr...
Early reports indicate that long non-coding RNAs (lncRNAs) are novel regulators of biological responses. However, their role in the human innate immune response, which provides the initial defence against infection, is largely unexplored. To address this issue, here we characterize the long non-coding RNA transcriptome in primary human monocytes us...
Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evi...
Multidimensional scaling plot of first two components. Multidimensional scaling analysis illustrating the first two components of Identity-By-State similarity for all FIS-affected (red squares) and controls (blue circles) used in the genome-wide association analysis. A permutation test (10,000 permutations) for between-group IBS differences showed...
Panel of 228 microsatellite markers used in linkage and homozygosity mapping.
(DOC)
Observed versus expected log10(P). A Q-Q plot showing the distribution of expected versus observed –log10P for the basic association test with no adjustment. The pink diagonal shows the values expected under the null hypothesis. The observed –log10P values match the expected values along the major portion of the graph and deviate towards the end il...
Alignment of re-sequenced region from FIS pony to the EquCab2 reference sequence. Sequence from the FIS-affected pony was aligned to the EquCab2 reference sequence using the Artemis Comparison Tool (ACT) [32] to identify possible rearrangements, duplications or insertion/deletions. Red indicates alignment of the sequence. White regions indicate mis...
The Fell pony pedigrees used for linkage analysis. Affected (FIS) individuals are shown shaded in black and obligate carriers are indicated with a dot. Individuals that are neither affected or obligate carriers are shown un-shaded. Individuals also coloured yellow were genotyped and used for linkage and homozygosity mapping. Double lines indicate c...
Linkage analysis and homozygosity mapping of FIS using a genome-wide microsatellite set.
(DOC)
The Fell and Dales are rare native UK pony breeds at risk due to falling numbers, in-breeding, and inherited disease. Specifically, the lethal Mendelian recessive disease Foal Immunodeficiency Syndrome (FIS), which manifests as B-lymphocyte immunodeficiency and progressive anemia, is a substantial threat. A significant percentage (∼10%) of the Fell...
AnnotatedFunctionalSNP.xls. A comprehensive annotation of publicly available SNP (NCBI build 37) across QTL regions including Polyphen annotation.
(1.97 MB XLS)
GenesAndHaplotypes.xls. Haplotype block alleles across QTL regions
(1.02 MB XLS)
SNP validation.xls. Comparison of resequencing of Tir1 region on the Illumina system at the Wellcome Trust Sanger Institute and on the 454 system at the University of Liverpool.
(0.04 MB XLS)
Supporting Text referred to in the main text. Includes: additional methods on haplotype analysis and genotyping markers and primers; and additional SNP and CNV data.
(1.30 MB DOC)
African trypanosomes are protozoan parasites that cause "sleeping sickness" in humans and a similar disease in livestock. Trypanosomes also infect laboratory mice and three major quantitative trait loci (QTL) that regulate survival time after infection with T. congolense have been identified in two independent crosses between susceptible A/J and BA...
Next-generation sequencing technologies are revolutionizing genomics research. It is now possible to generate gigabase pairs of DNA sequence within a week without time-consuming cloning or massive infrastructure. This technology has recently been applied to the development of 'RNA-seq' techniques for sequencing cDNA from various organisms, with the...
Pseudogenes in the genome of S. suis strains P1/7, SC84 and BM407.
(0.15 MB DOC)
Rhamnose-based polysaccharide cluster of strain P1/7 A) Structure and functional organisation of the Rhamnose-based polysaccharide cluster of strain P1/7. B) Comparison of the Rhamnose-based polysaccharide cluster from S. suis P1/7 with the RGP rml and rgp gene clusters of Streptococcus mutans UA159. The comparison of the RGP clusters from the S. s...
Streptococcus suis orphan CDSs in the in the genome of S. suis strain P1/7.
(0.24 MB DOC)
Since the completion of the genome sequence of Saccharomyces cerevisiae in 1996 (refs 1, 2), there has been a large increase in complete genome sequences, accompanied by great advances in our understanding of genome evolution. Although little is known about the natural and life histories of yeasts in the wild, there are an increasing number of stud...
Streptococcus suis is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in humans. S. suis infections occur sporadically in human Europe and North America, but a recent major outbreak has been described in China with high levels of mortality. The mechanisms of S. suis pathogenesis in humans and pigs are poorly unde...
Bacterial infections of the lungs of cystic fibrosis (CF) patients cause major complications in the treatment of this common
genetic disease. Burkholderia cenocepacia infection is particularly problematic since this organism has high levels of antibiotic resistance, making it difficult to
eradicate; the resulting chronic infections are associated w...
Absence of ESAG7 from BES7.
(1.82 MB EPS)
Long-range restriction mapping of NEO-tagged clones.
(5.15 MB EPS)
Quantifying the difference in phylogenetic signal along the bloodstream expression site.
(1.97 MB EPS)
Diversity and recombination within BES coding and intergenic sequences.
(0.45 MB EPS)
Positively selected codons in ESAG proteins.
(0.32 MB EPS)
PFGE Southern blotting.
(2.68 MB EPS)
GARD analysis and interpretation using ESAG2 sequences as an example.
(5.49 MB EPS)
Additional Materials and Methods; Figure and Table legends of supporting data
(0.04 MB DOC)
Locations of breakpoints inferred by GARD analysis of ESAG alignments.
(0.38 MB EPS)
Non-synonymous substitution rates for ESAGs.
(0.35 MB EPS)
During the clonal expansion of cancer from an ancestral cell with an initiating oncogenic mutation to symptomatic neoplasm, the occurrence of somatic mutations (both driver and passenger) can be used to track the on-going evolution of the neoplasm. All subclones within a cancer are phylogenetically related, with the prevalence of each subclone dete...
Isolates of Salmonella enterica serovar Typhi (Typhi), a human-restricted bacterial pathogen that causes typhoid, show limited genetic variation. We generated whole-genome sequences for 19 Typhi isolates using 454 (Roche) and Solexa (Illumina) technologies. Isolates, including the previously sequenced CT18 and Ty2 isolates, were selected to represe...
Human cancers often carry many somatically acquired genomic rearrangements, some of which may be implicated in cancer development. However, conventional strategies for characterizing rearrangements are laborious and low-throughput and have low sensitivity or poor resolution. We used massively parallel sequencing to generate sequence reads from both...
The natural genetics of an organism is determined by the distribution of sequences of its genome. Here we present one- to four-fold, with some deeper, coverage of the genome sequences of over seventy isolates of the domesticated baker's yeast, _Saccharomyces cerevisiae_, and its closest relative, the wild _S. paradoxus_, which has never been associ...
Mycobacterium marinum, a ubiquitous pathogen of fish and amphibia, is a near relative of Mycobacterium tuberculosis, the etiologic agent of tuberculosis in humans. The genome of the M strain of M. marinum comprises a 6,636,827-bp circular chromosome with 5424 CDS, 10 prophages, and a 23-kb mercury-resistance plasmid. Prominent features are the very...
Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune...
Chlamydia trachomatis is the most common cause of sexually transmitted infections in the UK, a statistic that is also reflected globally. There are three biovariants of C. trachomatis: trachoma (serotypes A-C) and two sexually transmitted pathovars; serotypes D-K and lymphogranuloma venereum (LGV). Trachoma isolates and the sexually transmitted ser...
44 Trypanosoma brucei rhodesiense strains, isolated from humans at eight sites in Uganda between 1988-1992, have exhibited two distinct clinical forms. Isoenzyme analysis has linked this apparent difference in virulence to different zymodemes, the phenotypes of which have been replicated in mice. Using 6 microsatellite markers, 36 of these samples...
The process by which bacteria regulate flagellar expression is known as phase variation and in Salmonella enterica this process permits the expression of one of two flagellin genes, fliC or fljB, at any one time. Salmonella Typhi (S. Typhi) is normally not capable of phase variation of flagellar antigen expression as isolates only harbour the fliC...
Clostridium botulinum is a heterogeneous Gram-positive species that comprises four genetically and physiologically distinct groups of bacteria that share the ability to produce botulinum neurotoxin, the most poisonous toxin known to man, and the causative agent of botulism, a severe disease of humans and animals. We report here the complete genome...
