Tam P Sneddon

National Center for Biotechnology Information, Maryland, United States

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Publications (6)95.15 Total impact

  • Tam P Sneddon · Deanna M Church
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    ABSTRACT: Genomic structural variation (SV) can be thought of on a continuum from a single base pair insertion/deletion (INDEL) to large megabase-scale rearrangements involving insertions, deletions, duplications, inversions, or translocations of whole chromosomes or chromosome arms. These variants can occur in coding or noncoding DNA, they can be inherited or arise sporadically in the germline or somatic cells. Many of these events are segregating in the population and can be considered common alleles while others are new alleles and thus rare events. All species studied to date harbor structural variants and these may be benign, contributing to phenotypes such as sensory perception and immunity, or pathogenic resulting in genomic disorders including DiGeorge/velocardiofacial, Smith-Margenis, Williams-Beuren, and Prader-Willi syndromes. As structural variants are identified, validated, and their significance, origin, and prevalence are elucidated, it is of critical importance that these data be collected and collated in a way that can be easily accessed and analyzed. This chapter describes current structural variation online resources (see Fig. 1 and Table 1), highlights the challenges in capturing, storing, and displaying SV data, and discusses how dbVar and DGVa, the genomic structural variation databases developed at NCBI and EBI, respectively, were designed to address these issues.
    No preview · Article · Jan 2012 · Methods in molecular biology (Clifton, N.J.)
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    Preview · Article · Oct 2010 · Nature Genetics
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    ABSTRACT: Assays for gamma-glutamyl transferase (GGT1, EC 2.3.2.2) activity in blood are widely used in a clinical setting to measure tissue damage. The well-characterized GGT1 is an extracellular enzyme that is anchored to the plasma membrane of cells. There, it hydrolyzes and transfers gamma-glutamyl moieties from glutathione and other gamma-glutamyl compounds to acceptors. As such, it has a critical function in the metabolism of glutathione and in the conversion of the leukotriene LTC4 to LTD4. GGT deficiency in man is rare and for the few patients reported to date, mutations in GGT1 have not been described. These patients do secrete glutathione in urine and fail to metabolize LTC4. Earlier pre-genome investigations had indicated that besides GGT1, the human genome contains additional related genes or sequences. These sequences were given multiple different names, leading to inconsistencies and confusion. Here we systematically evaluated all human sequences related to GGT1 using genomic and cDNA database searches and identified thirteen genes belonging to the extended GGT family, of which at least six appear to be active. In collaboration with the HUGO Gene Nomenclature Committee (HGNC) we have designated possible active genes with nucleotide or amino acid sequence similarity to GGT1, as GGT5 (formerly GGL, GGTLA1/GGT-rel), GGT6 (formerly rat ggt6 homologue) and GGT7 (formerly GGTL3, GGT4). Two loci have the potential to encode only the light chain portion of GGT and have now been designated GGTLC1 (formerly GGTL6, GGTLA4) and GGTLC2. Of the five full-length genes, three lack of significant nucleotide sequence homology but have significant (GGT5, GGT7) or very limited (GGT6) amino acid similarity to GGT1 and belong to separate families. GGT6 and GGT7 have not yet been described, raising the possibility that leukotriene synthesis, glutathione metabolism or gamma-glutamyl transfer is regulated by their, as of yet uncharacterized, enzymatic activities. In view of the widespread clinical use of assays that measure gamma-glutamyl transfer activity, this would appear to be of significant interest.
    No preview · Article · Jun 2008 · Human Genetics
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    ABSTRACT: The HUGO Gene Nomenclature Committee (HGNC) aims to assign a unique and ideally meaningful name and symbol to every human gene. The HGNC database currently comprises over 24 000 public records containing approved human gene nomenclature and associated gene information. Following our recent relocation to the European Bioinformatics Institute our homepage can now be found at http://www.genenames.org, with direct links to the searchable HGNC database and other related database resources, such as the HCOP orthology search tool and manually curated gene family webpages.
    Full-text · Article · Feb 2008 · Nucleic Acids Research
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    ABSTRACT: The International Human Genome Sequencing Consortium (IHGSC) recently completed a sequence of the human genome. As part of this project, we have focused on chromosome 8. Although some chromosomes exhibit extreme characteristics in terms of length, gene content, repeat content and fraction segmentally duplicated, chromosome 8 is distinctly typical in character, being very close to the genome median in each of these aspects. This work describes a finished sequence and gene catalogue for the chromosome, which represents just over 5% of the euchromatic human genome. A unique feature of the chromosome is a vast region of approximately 15 megabases on distal 8p that appears to have a strikingly high mutation rate, which has accelerated in the hominids relative to other sequenced mammals. This fast-evolving region contains a number of genes related to innate immunity and the nervous system, including loci that appear to be under positive selection--these include the major defensin (DEF) gene cluster and MCPH1, a gene that may have contributed to the evolution of expanded brain size in the great apes. The data from chromosome 8 should allow a better understanding of both normal and disease biology and genome evolution.
    Preview · Article · Feb 2006 · Nature
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    ABSTRACT: The HUGO Gene Nomenclature Committee (HGNC) aims to give every human gene a unique and ideally meaningful name and symbol. The HGNC database, previously known as Genew, contains over 22 000 public records with approved human gene nomenclature and associated information. The database has undergone major improvements throughout the last year, is publicly available for online searching at http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/searchgenes.pl and has a new custom downloads interface at http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/gdlw.pl.
    Full-text · Article · Feb 2006 · Nucleic Acids Research