Christine Lloyd
Wellcome Trust Sanger Institute
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Featured researches published by Christine Lloyd.
Nature | 2011
Mathieu Joron; Lise Frézal; Robert T. Jones; Nicola Chamberlain; Siu Fai Lee; Christoph R. Haag; Annabel Whibley; Michel Becuwe; Simon W. Baxter; Laura Ferguson; Paul Wilkinson; Camilo Salazar; Claire Davidson; Richard Clark; Michael A. Quail; Helen Beasley; Rebecca Glithero; Christine Lloyd; Sarah Sims; Matthew C. Jones; Jane Rogers; Chris D. Jiggins; Richard H. ffrench-Constant
Supergenes are tight clusters of loci that facilitate the co-segregation of adaptive variation, providing integrated control of complex adaptive phenotypes. Polymorphic supergenes, in which specific combinations of traits are maintained within a single population, were first described for ‘pin’ and ‘thrum’ floral types in Primula and Fagopyrum, but classic examples are also found in insect mimicry and snail morphology. Understanding the evolutionary mechanisms that generate these co-adapted gene sets, as well as the mode of limiting the production of unfit recombinant forms, remains a substantial challenge. Here we show that individual wing-pattern morphs in the polymorphic mimetic butterfly Heliconius numata are associated with different genomic rearrangements at the supergene locus P. These rearrangements tighten the genetic linkage between at least two colour-pattern loci that are known to recombine in closely related species, with complete suppression of recombination being observed in experimental crosses across a 400-kilobase interval containing at least 18 genes. In natural populations, notable patterns of linkage disequilibrium (LD) are observed across the entire P region. The resulting divergent haplotype clades and inversion breakpoints are found in complete association with wing-pattern morphs. Our results indicate that allelic combinations at known wing-patterning loci have become locked together in a polymorphic rearrangement at the P locus, forming a supergene that acts as a simple switch between complex adaptive phenotypes found in sympatry. These findings highlight how genomic rearrangements can have a central role in the coexistence of adaptive phenotypes involving several genes acting in concert, by locally limiting recombination and gene flow.
PLOS Neglected Tropical Diseases | 2012
Anna V. Protasio; Isheng J. Tsai; A. K. Babbage; Sarah Nichol; Martin Hunt; Martin Aslett; Nishadi De Silva; Giles S. Velarde; Timothy J. C. Anderson; Richard Clark; Claire Davidson; Gary P. Dillon; Nancy Holroyd; Philip T. LoVerde; Christine Lloyd; Jacquelline McQuillan; Guilherme Oliveira; Thomas D. Otto; Sophia J. Parker-Manuel; Michael A. Quail; R. Alan Wilson; Adhemar Zerlotini; David W. Dunne; Matthew Berriman
Schistosomiasis is one of the most prevalent parasitic diseases, affecting millions of people in developing countries. Amongst the human-infective species, Schistosoma mansoni is also the most commonly used in the laboratory and here we present the systematic improvement of its draft genome. We used Sanger capillary and deep-coverage Illumina sequencing from clonal worms to upgrade the highly fragmented draft 380 Mb genome to one with only 885 scaffolds and more than 81% of the bases organised into chromosomes. We have also used transcriptome sequencing (RNA-seq) from four time points in the parasites life cycle to refine gene predictions and profile their expression. More than 45% of predicted genes have been extensively modified and the total number has been reduced from 11,807 to 10,852. Using the new version of the genome, we identified trans-splicing events occurring in at least 11% of genes and identified clear cases where it is used to resolve polycistronic transcripts. We have produced a high-resolution map of temporal changes in expression for 9,535 genes, covering an unprecedented dynamic range for this organism. All of these data have been consolidated into a searchable format within the GeneDB (www.genedb.org) and SchistoDB (www.schistodb.net) databases. With further transcriptional profiling and genome sequencing increasingly accessible, the upgraded genome will form a fundamental dataset to underpin further advances in schistosome research.
Nature | 2006
Todd D. Taylor; Hideki Noguchi; Yasushi Totoki; Atsushi Toyoda; Yoko Kuroki; Ken Dewar; Christine Lloyd; Takehiko Itoh; Tadayuki Takeda; Dae-Won Kim; Xinwei She; Karen Barlow; Toby Bloom; Elspeth A. Bruford; Jean L. Chang; Christina A. Cuomo; Evan E. Eichler; Michael Fitzgerald; David B. Jaffe; Kurt LaButti; Robert Nicol; Hong Seog Park; Christopher Seaman; Carrie Sougnez; Xiaoping Yang; Andrew Zimmer; Michael C. Zody; Bruce W. Birren; Chad Nusbaum; Asao Fujiyama
Chromosome 11, although average in size, is one of the most gene- and disease-rich chromosomes in the human genome. Initial gene annotation indicates an average gene density of 11.6 genes per megabase, including 1,524 protein-coding genes, some of which were identified using novel methods, and 765 pseudogenes. One-quarter of the protein-coding genes shows overlap with other genes. Of the 856 olfactory receptor genes in the human genome, more than 40% are located in 28 single- and multi-gene clusters along this chromosome. Out of the 171 disorders currently attributed to the chromosome, 86 remain for which the underlying molecular basis is not yet known, including several mendelian traits, cancer and susceptibility loci. The high-quality data presented here—nearly 134.5 million base pairs representing 99.8% coverage of the euchromatic sequence—provide scientists with a solid foundation for understanding the genetic basis of these disorders and other biological phenomena.
Database | 2013
Laurens Wilming; Elizabeth Hart; Penny Coggill; Roger Horton; James Gilbert; Chris Clee; Matthew C. Jones; Christine Lloyd; Sophie Palmer; Sarah Sims; S. Whitehead; David Wiley; Stephan Beck; Jennifer Harrow
Major histocompatibility complex (MHC) genes play a critical role in vertebrate immune response and because the MHC is linked to a significant number of auto-immune and other diseases it is of great medical interest. Here we describe the clone-based sequencing and subsequent annotation of the MHC region of the gorilla genome. Because the MHC is subject to extensive variation, both structural and sequence-wise, it is not readily amenable to study in whole genome shotgun sequence such as the recently published gorilla genome. The variation of the MHC also makes it of evolutionary interest and therefore we analyse the sequence in the context of human and chimpanzee. In our comparisons with human and re-annotated chimpanzee MHC sequence we find that gorilla has a trimodular RCCX cluster, versus the reference human bimodular cluster, and additional copies of Class I (pseudo)genes between Gogo-K and Gogo-A (the orthologues of HLA-K and -A). We also find that Gogo-H (and Patr-H) is coding versus the HLA-H pseudogene and, conversely, there is a Gogo-DQB2 pseudogene versus the HLA-DQB2 coding gene. Our analysis, which is freely available through the VEGA genome browser, provides the research community with a comprehensive dataset for comparative and evolutionary research of the MHC.
Methods of Molecular Biology | 2012
Michael A. Quail; Lucy Matthews; Sarah Sims; Christine Lloyd; Helen Beasley; Simon W. Baxter
Sequencing large insert clones to completion is useful for characterizing specific genomic regions, identifying haplotypes, and closing gaps in whole genome sequencing projects. Despite being a standard technique in molecular laboratories, DNA sequencing using the Sanger method can be highly problematic when complex secondary structures or sequence repeats are encountered in genomic clones. Here, we describe methods to isolate DNA from a large insert clone (fosmid or BAC), subclone the sample, and sequence the region to the highest industry standard. Troubleshooting solutions for sequencing difficult templates are discussed.
Methods of Molecular Biology | 2012
Michael A. Quail; Lucy Matthews; Sarah Sims; Christine Lloyd; Helen Beasley; Simon W. Baxter
Large insert genome libraries have been a core resource required to sequence genomes, analyze haplotypes, and aid gene discovery. While next generation sequencing technologies are revolutionizing the field of genomics, traditional genome libraries will still be required for accurate genome assembly. Their utility is also being extended to functional studies for understanding DNA regulatory elements. Here, we present a detailed method for constructing genomic fosmid libraries, testing for common contaminants, gridding the library to nylon membranes, then hybridizing the library membranes with a radiolabeled probe to identify corresponding genomic clones. While this chapter focuses on fosmid libraries, many of these steps can also be applied to bacterial artificial chromosome libraries.
Nature | 1994
Richard Wilson; R. Ainscough; K. Anderson; C. Baynes; M. Berks; James K. Bonfield; John Burton; M. Connell; T. Copsey; John A. Cooper; Alan Coulson; M. Craxton; Simon Dear; Z. Du; Richard Durbin; Anthony Favello; Audrey Fraser; L. Fulton; A. Gardner; Philip Green; Trevor Hawkins; LaDeana W. Hillier; M. Jier; L. Johnston; Matthew C. Jones; J. K. Kershaw; J. Kirsten; N. Laisster; P. Latreille; J. Lightning