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GST Primary GST Primary Best Strategies for Health Care Quality Im... Best Strategies for Health Care Quality Improvement - Diabetes Quality Improvement Strategies for Antibio... Kathryn McDonald, Stanford-UCSF Evidence-b... Systematic review assessing the effect of ... Quality Improvement Strategies for Antibiotics Management Kathryn McDonald, Stanford-UCSF Evidence-based Practice Center, 117 Encina Commons, Stanford, CA 94305-6019, Kathy.mcdonald@stanford.edu Systematic review assessing the effect of quality improvement strategies on appropriate prescribing of antibiotics and appropriate choice of antibiotics. Adherence Adherence Assistive Devices Assistive Devices Childhood Burn Hanson MacMillan Childhood Burn Hanson MacMillan CLSA_9 CLSA_9 Cyberabuse Cyberabuse Cognitive Behavioural Therapy for Violent ... This review included randomized trials abo... Cognitive Behavioural Therapy for Violent Men who Batter Their Partners This review included randomized trials about the effects of cognitive behavioral therapy on domestic violence. The intervention included programs based on the Duluth Model. The violence had to be committed by a male toward his female partner. The violence also had to be physical. The primary outcomes were new arrests and convictions, and new reports of violence. CABG vs PCI CABG vs PCI Quality Improvement Strategies for Prevent... Quality Improvement Strategies for Preventing Nosocomial Infections (Created 17-Feb-06) Quality Improvement Strategies for Asthma ... Quality Improvement Strategies for Asthma Control Erectile Dysfunction (Created 30-Jan-06) Erectile Dysfunction (Created 30-Jan-06) Inequality - Smoking Cessation to Reduce S... This review was the first part of a projec... Inequality - Smoking Cessation to Reduce Socio-Economic Differences This review was the first part of a project about inequality. It included randomized trials about the effect of smoking cessation interventions on reducing socio-economic differences. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Diet and Physical Activity to Reduce Socio... This review was the second part in a proje... Diet and Physical Activity to Reduce Socio-Economic Differences This review was the second part in a project about inequality. It included randomized trials about the effect of interventions on reducing socio-economic differences in diet and physical activity. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Workfare The data in SRS are not identical to the d... Workfare The data in SRS are not identical to the data in the published report. We used SRS only for an updated search. The review included randomized trials about the effect of welfare-to-work programs. Participants were welfare recipients. There were basically two types of programs. The educational type tried to build knowledge and skills in order to help the welfare recipients acquire jobs that could support them economically. The "work first" approach was more aimed at getting the participants quickly into a job. Exercise interventions for the management ... The objective of this systematic review wa... Exercise interventions for the management of frailty The objective of this systematic review was to examine the effectiveness of current exercise interventions on the management of frailty. A comprehensive search of Medline, Embase, Psycinfo, Cinahl, Scopus, Ageline, Eric, and SportDiscus databases was conducted and produced 1808 citations. So far we have completed 2 levels of “title and abstract” screening and we ended up with 262 articles. We have just started the full text screening. Eligibility criteria included original studies whose participants were identified as frail or prefrail with specific criteria and in which structured physical activity was included as at least one component of the intervention. Create a free account, build a dictionary with saved terms to re-use later! Public Domestic Violence - Using Cognitive Behavior Therapy Smoking Cessation to Reduce Socio-Economic Differences Diet and Physical Activity to Reduce Socio-Economic Differences Workfare Exercise Interventions for the Management of Frailty Search     Simple Advanced Refine (4 coded questions)  Any of these:   Exact Phrase: All of these: None of these: Author: Periodical: Projects: No restrictions   Libraries: Public   Select SRS Projects Show Saved Terms Select Library Show articles that do not have abstracts  Type of Article Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 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Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT Humans or Animals Humans Animals Ages All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined Language English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French Results(1-25 of 103) Sort By: Publication Date Relevance Took: 1.677 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 5 1 2 3 4 > Last >> (103 articles found) Termination of DNA synthesis by N6-alkylated, not 3'-O-alkylated, photocleavable 2'-deoxyadenosine triphosphates. 2007 Weidong Wu,Brian P Stupi,Vladislav A Litosh,Dena Mansouri,Demetra Farley,Sidney Morris,Sherry Metzker,Michael L Metzker The Human Genome Project has facilitated the sequencing of many species, yet the current Sanger method is too expensive, labor intensive and time consuming to accomplish medical resequencing of human genomes en masse. Of the 'next-generation' technologies, cyclic reversible termination (CRT) is a p... ( view more )romising method with the goal of producing accurate sequence information at a fraction of the cost and effort. The foundation of this approach is the reversible terminator (RT), its chemical and biological properties of which directly impact the performance of the sequencing technology. Here, we have discovered a novel paradigm in RT chemistry, the attachment of a photocleavable, 2-nitrobenzyl group to the N(6)-position of 2'-deoxyadenosine triphosphate (dATP), which, upon incorporation, terminates DNA synthesis. The 3'-OH group of the N(6)-(2-nitrobenzyl)-dATP remains unblocked, providing favorable incorporation and termination properties for several commercially available DNA polymerases while maintaining good discrimination against mismatch incorporations. Upon removal of the 2-nitrobenzyl group with UV light, the natural nucleotide is restored without molecular scarring. A five-base experiment, illustrating the exquisite, stepwise addition through a homopolymer repeat, demonstrates the applicability of the N(6)-(2-nitrobenzyl)-dATP as an ideal RT for CRT sequencing. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Syntheses, photophysical properties, and application of through-bond energy-transfer cassettes for biotechnology. Oct 16, 2006 Guan-Sheng Jiao,Lars H Thoresen,Taeg Gyum Kim,Wade C Haaland,Feng Gao,Michael R Topp,Robin M Hochstrasser,Michael L Metzker,Kevin Burgess We have designed fluorescent "through-bond energy-transfer cassettes" that can harvest energy of a relatively short wavelength (e.g., 490 nm), and emit it at appreciably longer wavelengths without significant loss of intensity. Probes of this type could be particularly useful in biotechnology for m... ( view more )ultiplexing experiments in which several different outputs are to be observed from a single excitation source. Cassettes 1-4 were designed, prepared, and studied as model systems to achieve this end. They were synthesized through convergent routes that feature coupling of specially prepared fluorescein- and rhodamine-derived fragments. The four cassettes were shown to emit strongly, with highly efficient energy transfer. Their emission maxima cover a broad range of wavelengths (broader than the four dye cassettes currently used for most high-throughput DNA sequencing), and they exhibit faster energy-transfer rates than a similar through-space energy-transfer cassette. Specifically, energy-transfer rates in these cassettes is around 6-7 ps, in contrast to a similar through-space energy-transfer system shown to have a decay time of around 35 ps. Moreover, the cassettes are considerably more stable to photobleaching than fluorescein, even though they each contain fluorescein-derived donors. This was confirmed by bulk fluorescent measurements, and in single-molecule-detection studies. Modification of a commercial automated DNA-sequencing apparatus to detect the emissions of these four energy-transfer cassettes enabled single-color dye-primer sequencing. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles A deleterious mutation in SAMD9 causes normophosphatemic familial tumoral calcinosis. Oct 2006 Orit Topaz,Margarita Indelman,Ilana Chefetz,Dan Geiger,Aryeh Metzker,Yoram Altschuler,Mordechai Choder,Dani Bercovich,Jouni Uitto,Reuven Bergman,Gabriele Richard,Eli Sprecher Familial tumoral calcinosis (FTC) is a rare autosomal recessive disorder characterized by the progressive deposition of calcified masses in cutaneous and subcutaneous tissues, which results in painful ulcerative lesions and severe skin and bone infections. Two major types of FTC have been recognize... ( view more )d: hyperphosphatemic FTC (HFTC) and normophosphatemic FTC (NFTC). HFTC was recently shown to result from mutations in two different genes: GALNT3, which codes for a glycosyltransferase, and FGF23, which codes for a potent phosphaturic protein. To determine the molecular cause of NFTC, we performed homozygosity mapping in five affected families of Jewish Yemenite origin and mapped NFTC to 7q21-7q21.3. Mutation analysis revealed a homozygous mutation in the SAMD9 gene (K1495E), which was found to segregate with the disease in all families and to interfere with the protein expression. Our data suggest that SAMD9 is involved in the regulation of extraosseous calcification, a process of considerable importance in a wide range of diseases as common as atherosclerosis and autoimmune disorders. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The DNA sequence, annotation and analysis of human chromosome 3. Apr 27, 2006 Donna M Muzny,Steven E Scherer,Rajinder Kaul,Jing Wang,Jun Yu,Ralf Sudbrak,Christian J Buhay,Rui Chen,Andrew Cree,Yan Ding,Shannon Dugan-Rocha,Rachel Gill,Preethi Gunaratne,R Alan Harris,Alicia C Hawes,Judith Hernandez,Anne V Hodgson,Jennifer Hume,Andrew Jackson,Ziad Mohid Khan,Christie Kovar-Smith,Lora R Lewis,Ryan J Lozado,Michael L Metzker,Aleksandar Milosavljevic,George R Miner,Margaret B Morgan,Lynne V Nazareth,Graham Scott,Erica Sodergren,Xing-Zhi Song,David Steffen,Sharon Wei,David A Wheeler,Mathew W Wright,Kim C Worley,Ye Yuan,Zhengdong Zhang,Charles Q Adams,M Ali Ansari-Lari,Mulu Ayele,Mary J Brown,Guan Chen,Zhijian Chen,James Clendenning,Kerstin P Clerc-Blankenburg,Runsheng Chen,Zhu Chen,Clay Davis,Oliver Delgado,Huyen H Dinh,Wei Dong,Heather Draper,Stephen Ernst,Gang Fu,Manuel L Gonzalez-Garay,Dawn K Garcia,Will Gillett,Jun Gu,Bailin Hao,Eric Haugen,Paul Havlak,Xin He,Steffen Hennig,Songnian Hu,Wei Huang,Laronda R Jackson,Leni S Jacob,Susan H Kelly,Michael Kube,Ruth Levy,Zhangwan Li,Bin Liu,Jing Liu,Wen Liu,Jing Lu,Manjula Maheshwari,Bao-Viet Nguyen,Geoffrey O Okwuonu,Anthony Palmeiri,Shiran Pasternak,Lesette M Perez,Karen A Phelps,Farah J H Plopper,Boqin Qiang,Christopher Raymond,Ruben Rodriguez,Channakhone Saenphimmachak,Jireh Santibanez,Hua Shen,Yan Shen,Sandhya Subramanian,Paul E Tabor,Daniel Verduzco,Lenee Waldron,Jian Wang,Jun Wang,Qiaoyan Wang,Gabrielle A Williams,Gane K-S Wong,Zhijian Yao,JingKun Zhang,Xiuqing Zhang,Guoping Zhao,Jianling Zhou,Yang Zhou,David Nelson,Hans Lehrach,Richard Reinhardt,Susan L Naylor,Huanming Yang,Maynard Olson,George Weinstock,Richard A Gibbs After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chrom... ( view more )osomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The finished DNA sequence of human chromosome 12. Mar 16, 2006 Steven E Scherer,Donna M Muzny,Christian J Buhay,Rui Chen,Andrew Cree,Yan Ding,Shannon Dugan-Rocha,Rachel Gill,Preethi Gunaratne,R Alan Harris,Alicia C Hawes,Judith Hernandez,Anne V Hodgson,Jennifer Hume,Andrew Jackson,Ziad Mohid Khan,Christie Kovar-Smith,Lora R Lewis,Ryan J Lozado,Michael L Metzker,Aleksandar Milosavljevic,George R Miner,Kate T Montgomery,Margaret B Morgan,Lynne V Nazareth,Graham Scott,Erica Sodergren,Xing-Zhi Song,David Steffen,Ruth C Lovering,David A Wheeler,Kim C Worley,Yi Yuan,Zhengdong Zhang,Charles Q Adams,M Ali Ansari-Lari,Mulu Ayele,Mary J Brown,Guan Chen,Zhijian Chen,Kerstin P Clerc-Blankenburg,Clay Davis,Oliver Delgado,Huyen H Dinh,Heather Draper,Manuel L Gonzalez-Garay,Paul Havlak,Laronda R Jackson,Leni S Jacob,Susan H Kelly,Li Li,Zhangwan Li,Jing Liu,Wen Liu,Jing Lu,Manjula Maheshwari,Bao-Viet Nguyen,Geoffrey O Okwuonu,Shiran Pasternak,Lesette M Perez,Farah J H Plopper,Jireh Santibanez,Hua Shen,Paul E Tabor,Daniel Verduzco,Lenee Waldron,Qiaoyan Wang,Gabrielle A Williams,Jingkun Zhang,Jianling Zhou,Carlana C Allen,Anita G Amin,Vivian Anyalebechi,Michael Bailey,Joseph A Barbaria,Kesha E Bimage,Nathaniel P Bryant,Paula E Burch,Carrie E Burkett,Kevin L Burrell,Eliana Calderon,Veronica Cardenas,Kelvin Carter,Kristal Casias,Iracema Cavazos,Sandra R Cavazos,Heather Ceasar,Joseph Chacko,Sheryl N Chan,Dean Chavez,Constantine Christopoulos,Joseph Chu,Raynard Cockrell,Caroline D Cox,Michelle Dang,Stephanie R Dathorne,Robert David,Candi Mon'Et Davis,Latarsha Davy-Carroll,Denise R Deshazo,Jeremy E Donlin,Lisa D'Souza,Kristy A Eaves,Amy Egan,Alexandra J Emery-Cohen,Michael Escotto,Nicole Flagg,Lisa D Forbes,Abdul M Gabisi,Melissa Garza,Cerissa Hamilton,Nicholas Henderson,Omar Hernandez,Sandra Hines,Marilyn E Hogues,Mei Huang,DeVincent G Idlebird,Rudy Johnson,Angela Jolivet,Sally Jones,Ryan Kagan,Laquisha M King,Belita Leal,Heather Lebow,Sandra Lee,Jaclyn M LeVan,Lakeshia C Lewis,Pamela London,Lorna M Lorensuhewa,Hermela Loulseged,Demetria A Lovett,Alice Lucier,Raymond L Lucier,Jie Ma,Renita C Madu,Patricia Mapua,Ashley D Martindale,Evangelina Martinez,Elizabeth Massey,Samantha Mawhiney,Michael G Meador,Sylvia Mendez,Christian Mercado,Iracema C Mercado,Christina E Merritt,Zachary L Miner,Emmanuel Minja,Teresa Mitchell,Farida Mohabbat,Khatera Mohabbat,Baize Montgomery,Niki Moore,Sidney Morris,Mala Munidasa,Robin N Ngo,Ngoc B Nguyen,Elizabeth Nickerson,Ogechi O Nwaokelemeh,Stanley Nwokenkwo,Melissa Obregon,Maryann Oguh,Njideka Oragunye,Rodolfo J Oviedo,Bridgette J Parish,David N Parker,Julia Parrish,Kenya L Parks,Heidie A Paul,Brett A Payton,Agapito Perez,William Perrin,Adam Pickens,Eltrick L Primus,Ling-Ling Pu,Maria Puazo,Miyo M Quiles,Juana B Quiroz,Dina Rabata,Kacy Reeves,San Juana Ruiz,Hongmei Shao,Ida Sisson,Titilola Sonaike,Richard P Sorelle,Angelica E Sutton,Amanda F Svatek,Leah Anne Svetz,Kavitha S Tamerisa,Tineace R Taylor,Brian Teague,Nicole Thomas,Rachel D Thorn,Zulma Y Trejos,Brenda K Trevino,Ogechi N Ukegbu,Jeremy B Urban,Lydia I Vasquez,Virginia A Vera,Donna M Villasana,Ling Wang,Stephanie Ward-Moore,James T Warren,Xuehong Wei,Flower White,Angela L Williamson,Regina Wleczyk,Hailey S Wooden,Steven H Wooden,Jennifer Yen,Lillienne Yoon,Vivienne Yoon,Sara E Zorrilla,David Nelson,Raju Kucherlapati,George Weinstock,Richard A Gibbs,Baylor College of Medicine Human Genome Sequencing Center Sequence Production Team Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12... ( view more ), which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles l7Rn6 encodes a novel protein required for clara cell function in mouse lung development. Jan 2006 Rodrigo Fernández-Valdivia,Ying Zhang,Sonia Pai,Michael L Metzker,Armin Schumacher The highly secretory Clara cells play a pivotal role in protecting the lung against inflammation and oxidative stress. This study reports the positional cloning of a novel protein required for Clara cell physiology in mouse lung development. The perinatal lethal N-ethyl-N-nitrosourea-induced l7Rn6(... ( view more )4234SB) allele contained a nonsense mutation in the previously hypothetical gene NM_026304 on chromosome 7. Whereas l7Rn6 mRNA levels were indistinguishable from wild type, l7Rn6(4234SB) homozygotes exhibited decreased expression of the truncated protein, suggesting protein instability. During late gestation, l7Rn6 was widely expressed in the cytoplasm of lung epithelial cells, whereas perinatal expression was restricted to the bronchiolar epithelium. Homozygosity for the l7Rn6(4234SB) allele did not affect early steps in lung patterning, growth, or cellular differentiation. Rather, mutant lungs demonstrated severe emphysematous enlargement of the distal respiratory sacs at birth. Clara cell pathophysiology was evident from decreased cytoplasmic CCSP and SP-B protein levels, enlargement and disorganization of the Golgi complex, and formation of aberrant vesicular structures. Additional support for a role in the secretory pathway derived from l7Rn6 localization to the endoplasmic reticulum. Thus, l7Rn6 represents a novel protein required for organization and/or function of the secretory apparatus in Clara cells in mouse lung. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Emerging technologies in DNA sequencing. Dec 2005 Michael L Metzker Demand for DNA sequence information has never been greater, yet current Sanger technology is too costly, time consuming, and labor intensive to meet this ongoing demand. Applications span numerous research interests, including sequence variation studies, comparative genomics and evolution, forensic... ( view more )s, and diagnostic and applied therapeutics. Several emerging technologies show promise of delivering next-generation solutions for fast and affordable genome sequencing. In this review article, the DNA polymerase-dependent strategies of Sanger sequencing, single nucleotide addition, and cyclic reversible termination are discussed to highlight recent advances and potential challenges these technologies face in their development for ultrafast DNA sequencing. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Pediatric cutaneous mastocytosis: a review of 180 patients. May 2005 Dan Ben-Amitai,Aryeh Metzker,Herman A Cohen BACKGROUND: Mastocytosis is a heterogeneous group of diseases characterized by the abnormal infiltration of mast cells in the skin and, sometimes, other organs. Some patients may experience symptoms related to mast cell mediator release. OBJECTIVE: To analyze the clinical features of cutaneous mast... ( view more )ocytosis in a large series of children. METHODS: We conducted a file review of all children clinically diagnosed with cutaneous mastocytosis in our department over the last 20 years. We evaluated gender, age at onset, character and distribution of the lesions, associated symptoms, and course of the disease. RESULTS: Altogether, 180 patients with cutaneous mastocytosis were identified. The male to female ratio was 1.5:1. About one-third of patients had a mastocytoma, which was present at birth in over 40% and appeared during the first year of life in most of the remainder. Urticaria pigmentosa was noted in 65% of the patients, presenting at birth in 20% and during the first year in most of the remainder. The majority of lesions was distributed over the trunk and limbs. Different kinds of associated symptoms were noted. Prognosis in general was good. Only 11% of the cases, all urticaria pigmentosa, were familial. CONCLUSIONS: Most cases of pediatric mastocytosis are sporadic and appear during the first 2 years of life, especially on the trunk. Urticaria pigmentosa is the most frequent variant. The prognosis of pediatric mastocytosis, in general, is good. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Color-blind fluorescence detection for four-color DNA sequencing. Apr 12, 2005 Ernest K Lewis,Wade C Haaland,Freddy Nguyen,Daniel A Heller,Matthew J Allen,Robert R MacGregor,C Scott Berger,Britain Willingham,Lori A Burns,Graham B I Scott,Carter Kittrell,Bruce R Johnson,Robert F Curl,Michael L Metzker We present an approach called pulsed multiline excitation (PME) for measurements of multicomponent, fluorescence species and demonstrate its application in capillary electrophoresis for DNA sequencing. To fully demonstrate the advantages of PME, a fluorescent dye set has been developed whose absorp... ( view more )tion maxima span virtually the entire visible spectrum. Unlike emission wavelength-dependent approaches for identifying fluorescent species, the removal of the spectral component in PME confers a number of advantages including higher and normalized signals from all dyes present in the assay, the elimination of spectral cross-talk between dyes, and higher signal collection efficiency. Base-calling is unambiguously determined once dye mobility corrections are made. These advantages translate into significantly enhanced signal quality as illustrated in the primary DNA sequencing data and provide a means for achieving accurate base-calling at lower reagent concentrations. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The DNA sequence of the human X chromosome. Mar 17, 2005 Mark T Ross,Darren V Grafham,Alison J Coffey,Steven Scherer,Kirsten McLay,Donna Muzny,Matthias Platzer,Gareth R Howell,Christine Burrows,Christine P Bird,Adam Frankish,Frances L Lovell,Kevin L Howe,Jennifer L Ashurst,Robert S Fulton,Ralf Sudbrak,Gaiping Wen,Matthew C Jones,Matthew E Hurles,T Daniel Andrews,Carol E Scott,Stephen Searle,Juliane Ramser,Adam Whittaker,Rebecca Deadman,Nigel P Carter,Sarah E Hunt,Rui Chen,Andrew Cree,Preethi Gunaratne,Paul Havlak,Anne Hodgson,Michael L Metzker,Stephen Richards,Graham Scott,David Steffen,Erica Sodergren,David A Wheeler,Kim C Worley,Rachael Ainscough,Kerrie D Ambrose,M Ali Ansari-Lari,Swaroop Aradhya,Robert I S Ashwell,Anne K Babbage,Claire L Bagguley,Andrea Ballabio,Ruby Banerjee,Gary E Barker,Karen F Barlow,Ian P Barrett,Karen N Bates,David M Beare,Helen Beasley,Oliver Beasley,Alfred Beck,Graeme Bethel,Karin Blechschmidt,Nicola Brady,Sarah Bray-Allen,Anne M Bridgeman,Andrew J Brown,Mary J Brown,David Bonnin,Elspeth A Bruford,Christian Buhay,Paula Burch,Deborah Burford,Joanne Burgess,Wayne Burrill,John Burton,Jackie M Bye,Carol Carder,Laura Carrel,Joseph Chako,Joanne C Chapman,Dean Chavez,Ellson Chen,Guan Chen,Yuan Chen,Zhijian Chen,Craig Chinault,Alfredo Ciccodicola,Sue Y Clark,Graham Clarke,Chris M Clee,Sheila Clegg,Kerstin Clerc-Blankenburg,Karen Clifford,Vicky Cobley,Charlotte G Cole,Jen S Conquer,Nicole Corby,Richard E Connor,Robert David,Joy Davies,Clay Davis,John Davis,Oliver Delgado,Denise Deshazo,Pawandeep Dhami,Yan Ding,Huyen Dinh,Steve Dodsworth,Heather Draper,Shannon Dugan-Rocha,Andrew Dunham,Matthew Dunn,K James Durbin,Ireena Dutta,Tamsin Eades,Matthew Ellwood,Alexandra Emery-Cohen,Helen Errington,Kathryn L Evans,Louisa Faulkner,Fiona Francis,John Frankland,Audrey E Fraser,Petra Galgoczy,James Gilbert,Rachel Gill,Gernot Glöckner,Simon G Gregory,Susan Gribble,Coline Griffiths,Russell Grocock,Yanghong Gu,Rhian Gwilliam,Cerissa Hamilton,Elizabeth A Hart,Alicia Hawes,Paul D Heath,Katja Heitmann,Steffen Hennig,Judith Hernandez,Bernd Hinzmann,Sarah Ho,Michael Hoffs,Phillip J Howden,Elizabeth J Huckle,Jennifer Hume,Paul J Hunt,Adrienne R Hunt,Judith Isherwood,Leni Jacob,David Johnson,Sally Jones,Pieter J de Jong,Shirin S Joseph,Stephen Keenan,Susan Kelly,Joanne K Kershaw,Ziad Khan,Petra Kioschis,Sven Klages,Andrew J Knights,Anna Kosiura,Christie Kovar-Smith,Gavin K Laird,Cordelia Langford,Stephanie Lawlor,Margaret Leversha,Lora Lewis,Wen Liu,Christine Lloyd,David M Lloyd,Hermela Loulseged,Jane E Loveland,Jamieson D Lovell,Ryan Lozado,Jing Lu,Rachael Lyne,Jie Ma,Manjula Maheshwari,Lucy H Matthews,Jennifer McDowall,Stuart McLaren,Amanda McMurray,Patrick Meidl,Thomas Meitinger,Sarah Milne,George Miner,Shailesh L Mistry,Margaret Morgan,Sidney Morris,Ines Müller,James C Mullikin,Ngoc Nguyen,Gabriele Nordsiek,Gerald Nyakatura,Christopher N O'Dell,Geoffery Okwuonu,Sophie Palmer,Richard Pandian,David Parker,Julia Parrish,Shiran Pasternak,Dina Patel,Alex V Pearce,Danita M Pearson,Sarah E Pelan,Lesette Perez,Keith M Porter,Yvonne Ramsey,Kathrin Reichwald,Susan Rhodes,Kerry A Ridler,David Schlessinger,Mary G Schueler,Harminder K Sehra,Charles Shaw-Smith,Hua Shen,Elizabeth M Sheridan,Ratna Shownkeen,Carl D Skuce,Michelle L Smith,Elizabeth C Sotheran,Helen E Steingruber,Charles A Steward,Roy Storey,R Mark Swann,David Swarbreck,Paul E Tabor,Stefan Taudien,Tineace Taylor,Brian Teague,Karen Thomas,Andrea Thorpe,Kirsten Timms,Alan Tracey,Steve Trevanion,Anthony C Tromans,Michele d'Urso,Daniel Verduzco,Donna Villasana,Lenee Waldron,Melanie Wall,Qiaoyan Wang,James Warren,Georgina L Warry,Xuehong Wei,Anthony West,Siobhan L Whitehead,Mathew N Whiteley,Jane E Wilkinson,David L Willey,Gabrielle Williams,Leanne Williams,Angela Williamson,Helen Williamson,Laurens Wilming,Rebecca L Woodmansey,Paul W Wray,Jennifer Yen,Jingkun Zhang,Jianling Zhou,Huda Zoghbi,Sara Zorilla,David Buck,Richard Reinhardt,Annemarie Poustka,André Rosenthal,Hans Lehrach,Alfons Meindl,Patrick J Minx,Ladeana W Hillier,Huntington F Willard,Richard K Wilson,Robert H Waterston,Catherine M Rice,Mark Vaudin,Alan Coulson,David L Nelson,George Weinstock,John E Sulston,Richard Durbin,Tim Hubbard,Richard A Gibbs,Stephan Beck,Jane Rogers,David R Bentley The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise proc... ( view more )ess that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Comparative genome sequencing of Drosophila pseudoobscura: chromosomal, gene, and cis-element evolution. Jan 2005 Stephen Richards,Yue Liu,Brian R Bettencourt,Pavel Hradecky,Stan Letovsky,Rasmus Nielsen,Kevin Thornton,Melissa J Hubisz,Rui Chen,Richard P Meisel,Olivier Couronne,Sujun Hua,Mark A Smith,Peili Zhang,Jing Liu,Harmen J Bussemaker,Marinus F van Batenburg,Sally L Howells,Steven E Scherer,Erica Sodergren,Beverly B Matthews,Madeline A Crosby,Andrew J Schroeder,Daniel Ortiz-Barrientos,Catharine M Rives,Michael L Metzker,Donna M Muzny,Graham Scott,David Steffen,David A Wheeler,Kim C Worley,Paul Havlak,K James Durbin,Amy Egan,Rachel Gill,Jennifer Hume,Margaret B Morgan,George Miner,Cerissa Hamilton,Yanmei Huang,Lenée Waldron,Daniel Verduzco,Kerstin P Clerc-Blankenburg,Inna Dubchak,Mohamed A F Noor,Wyatt Anderson,Kevin P White,Andrew G Clark,Stephen W Schaeffer,William Gelbart,George M Weinstock,Richard A Gibbs We have sequenced the genome of a second Drosophila species, Drosophila pseudoobscura, and compared this to the genome sequence of Drosophila melanogaster, a primary model organism. Throughout evolution the vast majority of Drosophila genes have remained on the same chromosome arm, but within each ... ( view more )arm gene order has been extensively reshuffled, leading to a minimum of 921 syntenic blocks shared between the species. A repetitive sequence is found in the D. pseudoobscura genome at many junctions between adjacent syntenic blocks. Analysis of this novel repetitive element family suggests that recombination between offset elements may have given rise to many paracentric inversions, thereby contributing to the shuffling of gene order in the D. pseudoobscura lineage. Based on sequence similarity and synteny, 10,516 putative orthologs have been identified as a core gene set conserved over 25-55 million years (Myr) since the pseudoobscura/melanogaster divergence. Genes expressed in the testes had higher amino acid sequence divergence than the genome-wide average, consistent with the rapid evolution of sex-specific proteins. Cis-regulatory sequences are more conserved than random and nearby sequences between the species--but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a pattern of repeat-mediated chromosomal rearrangement, and high coadaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence between these species of Drosophila. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles An electronic perspective on the reduction of an n=n double bond at a conserved dimolybdenum core. Dec 3, 2004 Julia K Padden Metzker,John E McGrady Density functional theory has been used to assess the role of the bimetallic core in supporting reductive cleavage of the N=N double bond in [Cp2Mo2(mu-SMe)3(mu-eta1:eta1-HN=NPh)]+. The HOMO of the complex, the Mo-Mo delta orbital, plays a key role as a source of high-energy electrons, available fo... ( view more )r transfer into the vacant orbitals of the N=N unit. As a result, the metal centres cycle between the Mo(III) and Mo(IV) oxidation states. The symmetry of the Mo-Mo delta "buffer" orbital has a profound influence on the reaction pathway, because significant overlap with the redox-active orbital on the N=N unit (pi* or sigma*) is required for efficient electron transfer. The orthogonality of the Mo-Mo delta and N-N sigma* orbitals in the eta1:eta1 coordination mode ensures that electron transfer into the N-N sigma bond is effectively blocked, and a rate-limiting eta1:eta1-->eta1 rearrangement is a necessary precursor to cleavage of the bond. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Relationships between physical activity and motor skills in middle school children. Oct 2004 Julian A Reed,Andrea Metzker,D Allen Phillips The purpose of this study was to examine the relationships between physical activity measured as pedometer steps and performance on three motor skill tests. A secondary purpose was to determine if middle school children are meeting the recommendation for the number of daily steps. A sample (n =217)... ( view more ) of 6th, 7th and 8th grade students participated. Each subject wore a Digi-Walker pedometer for three consecutive days. Subjects additionally recorded their pedometer steps in two 45 min.-physical education classes. There were strong significant correlations between daily steps taken by boys and girls, pedometer steps during physical education class and the AAHPERD Passing Test and the Bass Stick Balance. Similar correlations were weaker for the Side-Step Agility Test. Multivariate analysis of variance was utilized to examine variability of the three skills test by sex and year in school. Differences between students in Grades 7 and 8 on the AAHPERD Passing Test were significant. In addition, significant differences between daily pedometer steps and steps during physical education between Grades 6 and 7 were observed. Boys and girls had similar means on the AAHPERD Passing Test and Bass Stick Balance Test, but not on the Side-Step Agility Test. Scores on the three movement skills tested in this study were not strongly related to physical activity of the entire sample. Steps taken by middle school children appear not to be related to these measures of motor skills. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis. Jun 2004 Orit Topaz,Daniel L Shurman,Reuven Bergman,Margarita Indelman,Paulina Ratajczak,Mordechai Mizrachi,Ziad Khamaysi,Doron Behar,Dan Petronius,Vered Friedman,Israel Zelikovic,Sharon Raimer,Arieh Metzker,Gabriele Richard,Eli Sprecher Familial tumoral calcinosis (FTC; OMIM 211900) is a severe autosomal recessive metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Using linkage analysis, we mapped the gene underlying FTC to 2q24-q31. This region includes the ... ( view more )gene GALNT3, which encodes a glycosyltransferase responsible for initiating mucin-type O-glycosylation. Sequence analysis of GALNT3 identified biallelic deleterious mutations in all individuals with FTC, suggesting that defective post-translational modification underlies the disease. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Apr 1, 2004 Richard A Gibbs,George M Weinstock,Michael L Metzker,Donna M Muzny,Erica J Sodergren,Steven Scherer,Graham Scott,David Steffen,Kim C Worley,Paula E Burch,Geoffrey Okwuonu,Sandra Hines,Lora Lewis,Christine DeRamo,Oliver Delgado,Shannon Dugan-Rocha,George Miner,Margaret Morgan,Alicia Hawes,Rachel Gill, Celera,Robert A Holt,Mark D Adams,Peter G Amanatides,Holly Baden-Tillson,Mary Barnstead,Soo Chin,Cheryl A Evans,Steve Ferriera,Carl Fosler,Anna Glodek,Zhiping Gu,Don Jennings,Cheryl L Kraft,Trixie Nguyen,Cynthia M Pfannkoch,Cynthia Sitter,Granger G Sutton,J Craig Venter,Trevor Woodage,Douglas Smith,Hong-Mei Lee,Erik Gustafson,Patrick Cahill,Arnold Kana,Lynn Doucette-Stamm,Keith Weinstock,Kim Fechtel,Robert B Weiss,Diane M Dunn,Eric D Green,Robert W Blakesley,Gerard G Bouffard,Pieter J De Jong,Kazutoyo Osoegawa,Baoli Zhu,Marco Marra,Jacqueline Schein,Ian Bosdet,Chris Fjell,Steven Jones,Martin Krzywinski,Carrie Mathewson,Asim Siddiqui,Natasja Wye,John McPherson,Shaying Zhao,Claire M Fraser,Jyoti Shetty,Sofiya Shatsman,Keita Geer,Yixin Chen,Sofyia Abramzon,William C Nierman,Paul H Havlak,Rui Chen,K James Durbin,Amy Egan,Yanru Ren,Xing-Zhi Song,Bingshan Li,Yue Liu,Xiang Qin,Simon Cawley,Kim C Worley,A J Cooney,Lisa M D'Souza,Kirt Martin,Jia Qian Wu,Manuel L Gonzalez-Garay,Andrew R Jackson,Kenneth J Kalafus,Michael P McLeod,Aleksandar Milosavljevic,Davinder Virk,Andrei Volkov,David A Wheeler,Zhengdong Zhang,Jeffrey A Bailey,Evan E Eichler,Eray Tuzun,Ewan Birney,Emmanuel Mongin,Abel Ureta-Vidal,Cara Woodwark,Evgeny Zdobnov,Peer Bork,Mikita Suyama,David Torrents,Marina Alexandersson,Barbara J Trask,Janet M Young,Hui Huang,Huajun Wang,Heming Xing,Sue Daniels,Darryl Gietzen,Jeanette Schmidt,Kristian Stevens,Ursula Vitt,Jim Wingrove,Francisco Camara,M Mar Albà,Josep F Abril,Roderic Guigo,Arian Smit,Inna Dubchak,Edward M Rubin,Olivier Couronne,Alexander Poliakov,Norbert Hübner,Detlev Ganten,Claudia Goesele,Oliver Hummel,Thomas Kreitler,Young-Ae Lee,Jan Monti,Herbert Schulz,Heike Zimdahl,Heinz Himmelbauer,Hans Lehrach,Howard J Jacob,Susan Bromberg,Jo Gullings-Handley,Michael I Jensen-Seaman,Anne E Kwitek,Jozef Lazar,Dean Pasko,Peter J Tonellato,Simon Twigger,Chris P Ponting,Jose M Duarte,Stephen Rice,Leo Goodstadt,Scott A Beatson,Richard D Emes,Eitan E Winter,Caleb Webber,Petra Brandt,Gerald Nyakatura,Margaret Adetobi,Francesca Chiaromonte,Laura Elnitski,Pallavi Eswara,Ross C Hardison,Minmei Hou,Diana Kolbe,Kateryna Makova,Webb Miller,Anton Nekrutenko,Cathy Riemer,Scott Schwartz,James Taylor,Shan Yang,Yi Zhang,Klaus Lindpaintner,T Dan Andrews,Mario Caccamo,Michele Clamp,Laura Clarke,Valerie Curwen,Richard Durbin,Eduardo Eyras,Stephen M Searle,Gregory M Cooper,Serafim Batzoglou,Michael Brudno,Arend Sidow,Eric A Stone,J Craig Venter,Bret A Payseur,Guillaume Bourque,Carlos López-Otín,Xose S Puente,Kushal Chakrabarti,Sourav Chatterji,Colin Dewey,Lior Pachter,Nicolas Bray,Von Bing Yap,Anat Caspi,Glenn Tesler,Pavel A Pevzner,David Haussler,Krishna M Roskin,Robert Baertsch,Hiram Clawson,Terrence S Furey,Angie S Hinrichs,Donna Karolchik,William J Kent,Kate R Rosenbloom,Heather Trumbower,Matt Weirauch,David N Cooper,Peter D Stenson,Bin Ma,Michael Brent,Manimozhiyan Arumugam,David Shteynberg,Richard R Copley,Martin S Taylor,Harold Riethman,Uma Mudunuri,Jane Peterson,Mark Guyer,Adam Felsenfeld,Susan Old,Stephen Mockrin,Francis Collins,Rat Genome Sequencing Project Consortium The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over ... ( view more )90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Interaction of hairless and thyroid hormone receptor is not involved in the pathogenesis of atrichia with papular lesions. Apr 2004 Karima Djabali,Abraham Zlotogorski,Arye Metzker,Dani Ben-Amitai,Angela M Christiano Atrichia with papular lesions (APL) (MIM 209 500) is a rare autosomal recessive disease characterized by early onset of atrichia, followed by a papular eruption within the first years of life. Recent studies demonstrating linkage to chromosome 8p21 and further mutation detection in the hairless gen... ( view more )e (HR) have established the molecular basis of APL. This study describes the case of a 16-year-old female with APL due to a missense mutation, D1012N, in the hr-thyroid hormone receptor interacting domain 2 (TRID2) of the HR. Using functional and biochemical analysis, it was determined that this mutation does not significantly affect hr-thyroid hormone receptor interaction. This result suggests that the TRID2 domain either is dispensable in the hr-TR interaction or is not involved in the pathogenesis of APL. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Clinical and pathologic correlations in genetically distinct forms of atrichia. Dec 2003 Abraham Zlotogorski,Ze'ev Hochberg,Paradi Mirmirani,Arye Metzker,Dan Ben-Amitai,Amalia Martinez-Mir,Andrey A Panteleyev,Angela M Christiano BACKGROUND: The genetic basis of 2 distinct forms of atrichia with papules has recently been defined at the molecular level. In atrichia with papular lesions (APL; Online Mendelian Inheritance in Man [OMIM] 209500), mutations in the hairless gene on chromosome 8p21 have recently been identified. At... ( view more )richia with papules also occurs in the clinical setting of vitamin D-dependent rickets type IIA (VDDR IIA; OMIM 277440), resulting from mutations in the vitamin D receptor gene on chromosome 12q12-q14. Despite the distinct genetic basis for both forms of atrichia, the clinical findings are strikingly similar and exhibit classic pathognomonic features unique to this phenotype. We sought to document the clinical and molecular features of APL and VDDR IIA. OBSERVATIONS: Molecular analysis of the hairless and vitamin D receptor genes was performed on genomic DNA from probands and family members from 3 families with APL and 2 with VDDR IIA. We present a clinical and histologic comparison of atrichia in patients with APL and VDDR IIA and highlight the genetically heterogeneous basis of atrichia by identification of pathogenetic mutations. CONCLUSIONS: Increased awareness of these diseases will allow early diagnosis and potential therapeutic intervention for the rickets in VDDR IIA and avoidance of treatment of the atrichia in both APL and VDDR IIA. Their phenotype similarities suggest the possibility of a functional relationship between HR and VDR. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Rigid, conjugated, fluoresceinated thymidine triphosphates: syntheses and polymerase mediated incorporation into DNA analogues. Oct 6, 2003 Lars H Thoresen,Guan-Sheng Jiao,Wade C Haaland,Michael L Metzker,Kevin Burgess Syntheses of a unique set of energy transfer dye labeled nucleoside triphosphates, compounds 1-3, are described. Attempts to prepare these compounds were only successful if the triphosphorylation reaction was performed before coupling the dye to the nucleobase, and not the other way around. Compoun... ( view more )ds were prepared as both the 2'-deoxy (a) and 2',3'-dideoxy- (b) forms. They feature progressively longer rigid conjugated linkers connecting the nucleobase and the hydroxyxanthone moiety. UV spectra of the parent nucleosides 12-14 show that as the length of the linker increases so does the absorption of the donor in the 320-330 nm region, but with relatively little red-shift of the maxima. Fluorescence spectra of the same compounds show that radiation in the 320-330 nm region results in predominant emission from the fluorescein. When the linker is irradiated at 320 nm, the only significant emission observed corresponds to the hydroxyxanthone part of the molecules at 520 nm; this corresponds to an effective Stokes' shift of 200 nm. As the absorption at 320-330 nm by the linker increases with length, so does the intensity of the fluorescein emission. A gel assay was used to gauge relative incorporation efficiencies of compounds 1-3, dTTP, ddTTP, and 6-TAMRA-ddTTP. Throughout, the thermostable polymerase TaqFS was used, as it is the one most widely applied in high throughput DNA sequencing. This assay showed that only compounds 3 were incorporated efficiently; these have the longest linkers. Of these, the 2'-deoxy nucleoside 3 a was incorporated and did not prevent the polymerase from extending the chain further. The 2',3'-dideoxy nucleoside 3 b was incorporated only about 430 times less efficiently than ddTTP under the same conditions, and caused chain termination. The implications of these studies on modified sequencing protocols are discussed. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Linkage and association mapping of the LRP5 locus on chromosome 11q13 in type 1 diabetes. Jul 2003 Rebecca C J Twells,Charles A Mein,Felicity Payne,Riitta Veijola,Matthew Gilbey,Matthew Bright,Andrew Timms,Yusuke Nakagawa,Hywel Snook,Sarah Nutland,Helen E Rance,Philippa Carr,Frank Dudbridge,Heather J Cordell,Jason Cooper,Eva Tuomilehto-Wolf,Jaakko Tuomilehto,Michael Phillips,Michael Metzker,J Fred Hess,John A Todd Linkage of chromosome 11q13 to type 1 diabetes (T1D) was first reported from genome scans (Davies et al. 1994; Hashimoto et al. 1994) resulting in P <2.2 x 10(-5) (Luo et al. 1996) and designated IDDM4 ( insulin dependent diabetes mellitus 4). Association mapping under the linkage peak using 12 pol... ( view more )ymorphic microsatellite markers suggested some evidence of association with a two-marker haplotype, D11S1917*03-H0570POLYA*02, which was under-transmitted to affected siblings and over-transmitted to unaffected siblings ( P=1.5 x 10(-6)) (Nakagawa et al. 1998). Others have reported evidence for T1D association of the microsatellite marker D11S987, which is approximately 100 kb proximal to D11S1917 (Eckenrode et al. 2000). We have sequenced a 400-kb interval surrounding these loci and identified four genes, including the low-density lipoprotein receptor related protein (LRP5) gene, which has been considered as a functional candidate gene for T1D (Hey et al. 1998; Twells et al. 2001). Consequently, we have developed a comprehensive SNP map of the LRP5 gene region, and identified 95 SNPs encompassing 269 kb of genomic DNA, characterised the LD in the region and haplotypes (Twells et al. 2003). Here, we present our refined linkage curve of the IDDM4 region, comprising 32 microsatellite markers and 12 SNPs, providing a peak MLS=2.58, P=5 x 10(-4), at LRP5 g.17646G>T. The disease association data, largely focused in the LRP5 region with 1,106 T1D families, provided no further evidence for disease association at LRP5 or at D11S987. A second dataset, comprising 1,569 families from Finland, failed to replicate our previous findings at LRP5. The continued search for the variants of the putative IDDM4 locus will greatly benefit from the future development of a haplotype map of the genome. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. May 29, 2003 Hironori Ueda,Joanna M M Howson,Laura Esposito,Joanne Heward,Hywel Snook,Giselle Chamberlain,Daniel B Rainbow,Kara M D Hunter,Annabel N Smith,Gianfranco Di Genova,Mathias H Herr,Ingrid Dahlman,Felicity Payne,Deborah Smyth,Christopher Lowe,Rebecca C J Twells,Sarah Howlett,Barry Healy,Sarah Nutland,Helen E Rance,Vin Everett,Luc J Smink,Alex C Lam,Heather J Cordell,Neil M Walker,Cristina Bordin,John Hulme,Costantino Motzo,Francesco Cucca,J Fred Hess,Michael L Metzker,Jane Rogers,Simon Gregory,Amit Allahabadia,Ratnasingam Nithiyananthan,Eva Tuomilehto-Wolf,Jaakko Tuomilehto,Polly Bingley,Kathleen M Gillespie,Dag E Undlien,Kjersti S Rønningen,Cristian Guja,Constantin Ionescu-Tîrgovi?te,David A Savage,A Peter Maxwell,Dennis J Carson,Chris C Patterson,Jayne A Franklyn,David G Clayton,Laurence B Peterson,Linda S Wicker,John A Todd,Stephen C L Gough Genes and mechanisms involved in common complex diseases, such as the autoimmune disorders that affect approximately 5% of the population, remain obscure. Here we identify polymorphisms of the cytotoxic T lymphocyte antigen 4 gene (CTLA4)--which encodes a vital negative regulatory molecule of the i... ( view more )mmune system--as candidates for primary determinants of risk of the common autoimmune disorders Graves' disease, autoimmune hypothyroidism and type 1 diabetes. In humans, disease susceptibility was mapped to a non-coding 6.1 kb 3' region of CTLA4, the common allelic variation of which was correlated with lower messenger RNA levels of the soluble alternative splice form of CTLA4. In the mouse model of type 1 diabetes, susceptibility was also associated with variation in CTLA-4 gene splicing with reduced production of a splice form encoding a molecule lacking the CD80/CD86 ligand-binding domain. Genetic mapping of variants conferring a small disease risk can identify pathways in complex disorders, as exemplified by our discovery of inherited, quantitative alterations of CTLA4 contributing to autoimmune tissue destruction. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Haplotype structure, LD blocks, and uneven recombination within the LRP5 gene. May 2003 Rebecca C J Twells,Charles A Mein,Michael S Phillips,J Fred Hess,Riitta Veijola,Matthew Gilbey,Matthew Bright,Michael Metzker,Benedicte A Lie,Amanda Kingsnorth,Edward Gregory,Yusuke Nakagawa,Hywel Snook,William Y S Wang,Jennifer Masters,Gillian Johnson,Iain Eaves,Joanna M M Howson,David Clayton,Heather J Cordell,Sarah Nutland,Helen Rance,Philippa Carr,John A Todd Patterns of linkage disequilibrium (LD) in the human genome are beginning to be characterized, with a paucity of haplotype diversity in "LD blocks," interspersed by apparent "hot spots" of recombination. Previously, we cloned and physically characterized the low-density lipoprotein-receptor-related... ( view more ) protein 5 (LRP5) gene. Here, we have extensively analysed both LRP5 and its flanking three genes, spanning 269 kb, for single nucleotide polymorphisms (SNPs), and we present a comprehensive SNP map comprising 95 polymorphisms. Analysis revealed high levels of recombination across LRP5, including a hot-spot region from intron 1 to intron 7 of LRP5, where there are 109 recombinants/Mb (4882 meioses), in contrast to flanking regions of 14.6 recombinants/Mb. This region of high recombination could be delineated into three to four hot spots, one within a 601-bp interval. For LRP5, three haplotype blocks were identified, flanked by the hot spots. Each LD block comprised over 80% common haplotypes, concurring with a previous study of 14 genes that showed that common haplotypes account for at least 80% of all haplotypes. The identification of hot spots in between these LD blocks provides additional evidence that LD blocks are separated by areas of higher recombination. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Molecular evidence of HIV-1 transmission in a criminal case. Oct 29, 2002 Michael L Metzker,David P Mindell,Xiao-Mei Liu,Roger G Ptak,Richard A Gibbs,David M Hillis A gastroenterologist was convicted of attempted second-degree murder by injecting his former girlfriend with blood or blood-products obtained from an HIV type 1 (HIV-1)-infected patient under his care. Phylogenetic analyses of HIV-1 sequences were admitted and used as evidence in this case, represe... ( view more )nting the first use of phylogenetic analyses in a criminal court case in the United States. Phylogenetic analyses of HIV-1 reverse transcriptase and env DNA sequences isolated from the victim, the patient, and a local population sample of HIV-1-positive individuals showed the victim's HIV-1 sequences to be most closely related to and nested within a lineage comprised of the patient's HIV-1 sequences. This finding of paraphyly for the patient's sequences was consistent with the direction of transmission from the patient to the victim. Analysis of the victim's viral reverse transcriptase sequences revealed genotypes consistent with known mutations that confer resistance to AZT, similar to those genotypes found in the patient. A priori establishment of the patient and victim as a suspected transmission pair provided a clear hypothesis for phylogenetic testing. All phylogenetic models and both genes examined strongly supported the close relationship between the HIV-1 sequences of the patient and the victim. Resampling of blood from the suspected transmission pair and independent sequencing by different laboratories provided precaution against laboratory error. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Glass bead purification of plasmid template DNA for high throughput sequencing of mammalian genomes. Apr 1, 2002 Debra A Dederich,Geoffrey Okwuonu,Toni Garner,Amanda Denn,Angelica Sutton,Michael Escotto,Ashley Martindale,Oliver Delgado,Donna M Muzny,Richard A Gibbs,Michael L Metzker To meet the new challenge of generating the draft sequences of mammalian genomes, we describe the development of a novel high throughput 96-well method for the purification of plasmid DNA template using size-fractionated, acid-washed glass beads. Unlike most previously described approaches, the cur... ( view more )rent method has been designed and optimized to facilitate the direct binding of alcohol-precipitated plasmid DNA to glass beads from alkaline lysed bacterial cells containing the insoluble cellular aggregate material. Eliminating the tedious step of separating the cleared lysate significantly simplifies the method and improves throughput and reliability. During a 4 month period of 96-capillary DNA sequencing of the Rattus norvegicus genome at the Baylor College of Medicine Human Genome Sequencing Center, the average success rate and read length derived from >1 800 000 plasmid DNA templates prepared by the direct lysis/glass bead method were 82.2% and 516 bases, respectively. The cost of this direct lysis/glass bead method in September 2001 was approximately 10 cents per clone, which is a significant cost saving in high throughput genomic sequencing efforts. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Gossypol: a contraceptive for men. Apr 2002 Elsimar Metzker Coutinho Gossypol is a polyphenol isolated from the seed, roots, and stem of the cotton plant (Gossypium sp.). The substance, a yellow pigment similar to flavonoids, is present in cottonseed oil. In the plant, it acts as a natural defensive agent against predators, provoking infertility in insects. In most ... ( view more )animals, gossypol provokes infertility, and in man it causes spermatogenesis arrest at relatively low doses. Studies carried out in China, Africa, and Brazil have shown that the substance is well tolerated, causing no side effects that lead to discontinuation. The reported hypokalemia of early studies has not been confirmed in the latest trials. The only concern at present appears to be lack of reversibility in over 20% of subjects. Gossypol should be prescribed preferably to men who have completed their families or for those who would accept permanent infertility after a few years of use. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Cutis marmorata telangiectatica congenita and hypospadias: report of 4 cases. Jul 2001 D Ben-Amitai,P Merlob,A Metzker Cutis marmorata telangiectatica congenita (CMTC) is an uncommon sporadic congenital vascular anomaly. Of the 111 patients with CMTC examined in our clinic during the past 25 years, 4 were found to have hypospadias. All cases were sporadic. Although CMTC has been associated with various abnormalitie... ( view more )s, to our knowledge there are no reports in the literature of concurrent hypospadias. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Page 1 of 5 1 2 3 4 > Last >> (103 articles found)

      
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