近期的《美國人類遺傳學雜志》（American Journal of Human Genetics）刊登了英國倫敦大學一項最新研究,，研究人員通過基因工程對于攜帶有人類21號染色體的老鼠胚胎干細胞進行了研究,，結果發(fā)現(xiàn),，額外的21號染色體會干擾一個名為NRSF 或 REST的關鍵性的調控基因,。同時，研究人員還識別出了人類21號染色體上的一個基因DYRK1A,，該基因數(shù)量的增加會引發(fā)唐氏綜合癥的癥狀,。
唐氏綜合癥是人類最常見、也是第一種被確認的染色體病,。主要特征為低智商,，并伴有特殊面容。長期以來,，人們一直認為大部分唐氏綜合癥患者是由于在配子（生殖細胞）形成期或合子期（約在受精后24小時內(nèi)）細胞內(nèi)多了一條21號染色體所致,。但是，關于這種疾病造成腦發(fā)育異常的精細遺傳機制,，一直不為人所了解,。
在最新的研究中，科學家對經(jīng)過基因工程改良而攜帶有人類21號染色體的老鼠胚胎干細胞進行了研究,。結果發(fā)現(xiàn),，額外的21號染色體會干擾一個名為NRSF 或 REST的關鍵性調控基因，然后該受影響的基因會再去影響其它許多在胚胎干細胞階段控制細胞正常發(fā)育的基因,。此外，他們還識別出了人類21號染色體上的一個基因DYRK1A,，研究發(fā)現(xiàn)該基因數(shù)量增加會引起唐氏綜合癥的癥狀,。
研究人員下一步將對在胚胎干細胞階段控制細胞正常發(fā)育的基因研究，希望能為唐氏綜合癥疾病的基因治療開辟新的路徑,。（生物谷Bioon.com）
生物谷推薦原始出處：
American Journal of Human Genetics,，doi:10.1016/j.ajhg.2008.03.001，Rikke S. M?ller, Zeynep Tümer, and Vera M. Kalscheuer
Truncation of the Down Syndrome Candidate Gene DYRK1A in Two Unrelated Patients with Microcephaly
Rikke S. M?ller1, 2, Sabine Kübart3, Maria Hoeltzenbein3, Babett Heye4, Ida Vogel5, Christian P. Hansen2, Corinna Menzel3, Reinhard Ullmann3, Niels Tommerup1, Hans-Hilger Ropers3, Zeynep Tümer1, , and Vera M. Kalscheuer3
1Wilhelm Johannsen Centre for Functional Genome Research, Institute of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark 2Danish Epilepsy Centre, Dianalund, Kolonivej 1, 4293 Dianalund, Denmark 3Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany 4Institut für Soziale P?diatrie und Jugendmedizin der Universit?t München, Abteilung Genetik, Kinderzentrum München, 81377 München, Germany 5Department of Clinical Genetics, Aarhus University Hospital, The Bartholin Building, DK-8000 Aarhus C, Denmark
We have identified and characterized two unrelated patients with prenatal onset of microcephaly, intrauterine growth retardation, feeding problems, developmental delay, and febrile seizures/epilepsy who both carry a de novo balanced translocation that truncates the DYRK1A gene at chromosome 21q22.2. DYRK1A belongs to the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family, which is highly conserved throughout evolution. Given its localization in both the Down syndrome critical region and in the minimal region for partial monosomy 21, the gene has been studied intensively in animals and in humans, and DYRK1A has been proposed to be involved in the neurodevelopmental alterations associated with these syndromes. In the present study, we show that truncating mutations of DYRK1A result in a clinical phenotype including microcephaly.
