ORCID Profile
0000-0001-7720-0447
Current Organisations
GenomicsPLC
,
University of Oxford
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Oxford University Press (OUP)
Date: 17-01-2017
DOI: 10.1093/HMG/DDW412
Publisher: Springer Science and Business Media LLC
Date: 06-3011
DOI: 10.1038/NATURE10842
Publisher: eLife Sciences Publications, Ltd
Date: 26-02-2013
DOI: 10.7554/ELIFE.00348
Abstract: Two-thirds of gene promoters in mammals are associated with regions of non-methylated DNA, called CpG islands (CGIs), which counteract the repressive effects of DNA methylation on chromatin. In cold-blooded vertebrates, computational CGI predictions often reside away from gene promoters, suggesting a major ergence in gene promoter architecture across vertebrates. By experimentally identifying non-methylated DNA in the genomes of seven erse vertebrates, we instead reveal that non-methylated islands (NMIs) of DNA are a central feature of vertebrate gene promoters. Furthermore, NMIs are present at orthologous genes across vast evolutionary distances, revealing a surprising level of conservation in this epigenetic feature. By profiling NMIs in different tissues and developmental stages we uncover a unifying set of features that are central to the function of NMIs in vertebrates. Together these findings demonstrate an ancient logic for NMI usage at gene promoters and reveal an unprecedented level of epigenetic conservation across vertebrate evolution.
Publisher: Cold Spring Harbor Laboratory
Date: 24-08-2010
Abstract: Initially thought to play a restricted role in calcium homeostasis, the pleiotropic actions of vitamin D in biology and their clinical significance are only now becoming apparent. However, the mode of action of vitamin D, through its cognate nuclear vitamin D receptor (VDR), and its contribution to erse disorders, remain poorly understood. We determined VDR binding throughout the human genome using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq). After calcitriol stimulation, we identified 2776 genomic positions occupied by the VDR and 229 genes with significant changes in expression in response to vitamin D. VDR binding sites were significantly enriched near autoimmune and cancer associated genes identified from genome-wide association (GWA) studies. Notable genes with VDR binding included IRF8 , associated with MS, and PTPN2 associated with Crohn's disease and T1D. Furthermore, a number of single nucleotide polymorphism associations from GWA were located directly within VDR binding intervals, for ex le, rs13385731 associated with SLE and rs947474 associated with T1D. We also observed significant enrichment of VDR intervals within regions of positive selection among in iduals of Asian and European descent. ChIP-seq determination of transcription factor binding, in combination with GWA data, provides a powerful approach to further understanding the molecular bases of complex diseases.
Publisher: Springer Science and Business Media LLC
Date: 19-08-2011
Abstract: The thymus plays a critical role in the development and maturation of T-cells. Humans have a single thoracic thymus and presence of a second thymus is considered an anomaly. However, many vertebrates have multiple thymuses. The tammar wallaby has two thymuses: a thoracic thymus (typically found in all mammals) and a dominant cervical thymus. Researchers have known about the presence of the two wallaby thymuses since the 1800s, but no genome-wide research has been carried out into possible functional differences between the two thymic tissues. Here, we used pyrosequencing to compare the transcriptomes of a cervical and thoracic thymus from a single 178 day old tammar wallaby. We show that both the tammar thoracic and the cervical thymuses displayed gene expression profiles consistent with roles in T-cell development. Both thymuses expressed genes that mediate distinct phases of T-cells differentiation, including the initial commitment of blood stem cells to the T-lineage, the generation of T-cell receptor ersity and development of thymic epithelial cells. Crucial immune genes, such as chemokines were also present. Comparable patterns of expression of non-coding RNAs were seen. 67 genes differentially expressed between the two thymuses were detected, and the possible significance of these results are discussed. This is the first study comparing the transcriptomes of two thymuses from a single in idual. Our finding supports that both thymuses are functionally equivalent and drive T-cell development. These results are an important first step in the understanding of the genetic processes that govern marsupial immunity, and also allow us to begin to trace the evolution of the mammalian immune system.
Publisher: Springer Science and Business Media LLC
Date: 12-2005
DOI: 10.1038/NATURE04338
Abstract: Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic ersity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic ersity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
Publisher: Springer Science and Business Media LLC
Date: 05-2008
DOI: 10.1038/NATURE06936
Publisher: Elsevier BV
Date: 09-2014
Publisher: Springer Science and Business Media LLC
Date: 05-2007
DOI: 10.1038/NATURE05805
Abstract: We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to ersification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the ergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.
Publisher: Springer Science and Business Media LLC
Date: 11-2007
DOI: 10.1038/NATURE06341
Publisher: Springer Science and Business Media LLC
Date: 04-2010
DOI: 10.1038/NATURE08819
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: Germany
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Andreas Heger.