Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
2009-7-22
pubmed:abstractText
Down syndrome (DS), or trisomy 21, is a common disorder associated with several complex clinical phenotypes. Although several hypotheses have been put forward, it is unclear as to whether particular gene loci on chromosome 21 (HSA21) are sufficient to cause DS and its associated features. Here we present a high-resolution genetic map of DS phenotypes based on an analysis of 30 subjects carrying rare segmental trisomies of various regions of HSA21. By using state-of-the-art genomics technologies we mapped segmental trisomies at exon-level resolution and identified discrete regions of 1.8-16.3 Mb likely to be involved in the development of 8 DS phenotypes, 4 of which are congenital malformations, including acute megakaryocytic leukemia, transient myeloproliferative disorder, Hirschsprung disease, duodenal stenosis, imperforate anus, severe mental retardation, DS-Alzheimer Disease, and DS-specific congenital heart disease (DSCHD). Our DS-phenotypic maps located DSCHD to a <2-Mb interval. Furthermore, the map enabled us to present evidence against the necessary involvement of other loci as well as specific hypotheses that have been put forward in relation to the etiology of DS-i.e., the presence of a single DS consensus region and the sufficiency of DSCR1 and DYRK1A, or APP, in causing several severe DS phenotypes. Our study demonstrates the value of combining advanced genomics with cohorts of rare patients for studying DS, a prototype for the role of copy-number variation in complex disease.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-10523528, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-11178230, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-11179664, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-11280955, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-11953745, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-12225587, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-1367928, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-14738882, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-15273396, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-15286789, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-1531166, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-15499018, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-16140924, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-16179473, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-16369530, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-16492768, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-16537408, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-16554754, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-17122850, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-17237124, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-17412756, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-17551006, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-17663443, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-17901297, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-19002211, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-2073837, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-2147289, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-2149983, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-2301399, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-2527368, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-2527801, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-4276065, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-7698011, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-8055322, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-8197171, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-8808464, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-9143497, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-9426258, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-9600952, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-9632176, http://linkedlifedata.com/resource/pubmed/commentcorrection/19597142-9713998
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1091-6490
pubmed:author
pubmed-author:AylsworthArthur SAS, pubmed-author:BarlowGillian MGM, pubmed-author:CarpenterNancy JNJ, pubmed-author:ChenXiao-NingXN, pubmed-author:ClarkRobin DawnRD, pubmed-author:CohenMonika YMY, pubmed-author:DaiLiL, pubmed-author:DoranEricE, pubmed-author:ErdmanChandraC, pubmed-author:Falik-ZaccaiTziporaT, pubmed-author:GaoMichael CMC, pubmed-author:GersteinMark BMB, pubmed-author:GrubertFabianF, pubmed-author:KasowskiMayaM, pubmed-author:KorbelJan OJO, pubmed-author:KorenbergJulie RJR, pubmed-author:LangeKenK, pubmed-author:LewisSusan HSH, pubmed-author:LottIra TIT, pubmed-author:McGillivrayBarbara CBC, pubmed-author:MoeschlerJohn BJB, pubmed-author:PettenatiMark JMJ, pubmed-author:PueschelSiegfried MSM, pubmed-author:RaoKathleen WKW, pubmed-author:ShafferLisa GLG, pubmed-author:ShohatMordechaiM, pubmed-author:SnyderMichaelM, pubmed-author:SobelEric MEM, pubmed-author:Tirosh-WagnerTalT, pubmed-author:UrbanAlexander EckehartAE, pubmed-author:Van RiperAlexander JAJ, pubmed-author:WarburtonDorothyD, pubmed-author:WeissmanShermanS
pubmed:issnType
Electronic
pubmed:day
21
pubmed:volume
106
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12031-6
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
More...