幾個方面的證據(jù)都表明，“泛自閉癥障礙癥候群”（ASDs）、神經(jīng)發(fā)育和神經(jīng)精神類疾病都與遺傳有關(guān),，這些疾病的特征是語言溝通和社會互動能力受損。病癥在臨床和遺傳上的復雜性使得研究人員難以識別易感因子,，但本期Nature上發(fā)表的兩項相關(guān)聯(lián)的研究,，為這類疾病與遺傳有關(guān)提供了可靠證據(jù)。
第一項是整個基因組范圍內(nèi)的關(guān)聯(lián)研究,，識別出了6個與自閉癥有很強相關(guān)性的單核苷酸多態(tài)性,。這些變種分布在兩個編碼神經(jīng)細胞粘附分子（cadherins 9 和10）的基因之間，說明它們可能在ASD發(fā)病機理中有所涉及。第二項研究利用版本數(shù)變化篩選方法來識別ASDs患兒兩個主要基因通道中的基因變異,。這些變異在泛素通道中，該通道以前被發(fā)現(xiàn)與神經(jīng)類疾病有關(guān),；它們也在為神經(jīng)細胞粘附分子編碼的基因中,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 459, 528-533 (28 May 2009) | doi:10.1038/nature07999
Common genetic variants on 5p14.1 associate with autism spectrum disorders
Kai Wang1,22, Haitao Zhang1,22, Deqiong Ma2,22, Maja Bucan3, Joseph T. Glessner1, Brett S. Abrahams4, Daria Salyakina2, Marcin Imielinski1, Jonathan P. Bradfield1, Patrick M. A. Sleiman1, Cecilia E. Kim1, Cuiping Hou1, Edward Frackelton1, Rosetta Chiavacci1, Nagahide Takahashi5, Takeshi Sakurai5, Eric Rappaport6, Clara M. Lajonchere7, Jeffrey Munson8, Annette Estes8, Olena Korvatska8, Joseph Piven9, Lisa I. Sonnenblick4, Ana I. Alvarez Retuerto4, Edward I. Herman4, Hongmei Dong4, Ted Hutman4, Marian Sigman4, Sally Ozonoff10, Ami Klin11, Thomas Owley12, John A. Sweeney12, Camille W. Brune12, Rita M. Cantor13, Raphael Bernier8, John R. Gilbert2, Michael L. Cuccaro2, William M. McMahon14, Judith Miller14, Matthew W. State11, Thomas H. Wassink15, Hilary Coon14, Susan E. Levy6, Robert T. Schultz6, John I. Nurnberger16, Jonathan L. Haines17, James S. Sutcliffe18, Edwin H. Cook12, Nancy J. Minshew19, Joseph D. Buxbaum5,20, Geraldine Dawson8, Struan F. A. Grant1,6, Daniel H. Geschwind4, Margaret A. Pericak-Vance2, Gerard D. Schellenberg21 & Hakon Hakonarson1,6
Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental and neuropsychiatric disorders characterized by deficits in verbal communication, impairment of social interaction, and restricted and repetitive patterns of interests and behaviour. To identify common genetic risk factors underlying ASDs, here we present the results of genome-wide association studies on a cohort of 780 families (3,101 subjects) with affected children, and a second cohort of 1,204 affected subjects and 6,491 control subjects, all of whom were of European ancestry. Six single nucleotide polymorphisms between cadherin 10 (CDH10) and cadherin 9 (CDH9)—two genes encoding neuronal cell-adhesion molecules—revealed strong association signals, with the most significant SNP being rs4307059 (P = 3.4 10-8, odds ratio = 1.19). These signals were replicated in two independent cohorts, with combined P values ranging from 7.4 10-8 to 2.1 10-10. Our results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to our knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs.
