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科学家发现了21号染色体的几个关键区域可能导致唐氏综合征的症状。唐氏综合征是一种影响将近1/800的儿童的一种疾病，它是由于21号染色体的全部或者部分出现遗传重复造成的。这种染色体畸形导致了一些临床症状，包括认知能力和身体发育削弱，以及先天性心脏缺陷和白血病，但是许多造成这些症状的基因仍然未知。
通过研究携带罕见的21号染色体突变的患者，Julie
Korenberg及其同事构造了一个高分辨率的图，它发现了很可能导致了唐氏综合征症状的不连续的遗传区域。这组作者报告说他们发现了8个和这些症状有关的基因区域，其中4个造成了先天畸形。这份遗传图也证明了21号染色体的许多曾被认为和该病症状有密切关系的区域（例如单个唐氏综合征一致区）很可能对于该综合征的症状发展并不必要。这组作者说，这项研究可能帮助医生理解唐氏综合征的遗传原因并有助于治疗患者的帮助措施。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS July 13, 2009, doi: 10.1073/pnas.0813248106
The genetic architecture of Down syndrome
phenotypes revealed by high-resolution analysis of human segmental
trisomies
Jan O. Korbela,b,c,1, Tal Tirosh-Wagnerd,1,
Alexander Eckehart Urbane,f,1, Xiao-Ning Chend, Maya Kasowskie, Li
Daid, Fabian Grubertf, Chandra Erdmang, Michael C. Gaod, Ken
Langeh,i, Eric M. Sobelh, Gillian M. Barlowd, Arthur S.
Aylsworthj,k, Nancy J. Carpenterl, Robin Dawn Clarkm, Monika Y.
Cohenn, Eric Dorano, Tzipora Falik-Zaccaip, Susan O. Lewinq, Ira T.
Lotto, Barbara C. McGillivrayr, John B. Moeschlers, Mark J.
Pettenatit, Siegfried M. Pueschelu, Kathleen W. Raoj,k,v, Lisa G.
Shafferw, Mordechai Shohatx, Alexander J. Van Ripery, Dorothy
Warburtonz,aa, Sherman Weissmana, Mark B. Gersteina, Michael
Snydera,e,2 and Julie R. Korenbergd,h,bb,2
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.
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