扭转性肌张力障碍基因（DYT1）在人类9号染色体q34区域的精细定位：酵母人工染色体图谱及连锁不平衡

Fine localization of the torsion dystonia gene (DYT1) on human chromosome 9q34: YAC map and linkage disequilibrium.

作者信息

Ozelius L J, Hewett J, Kramer P, Bressman S B, Shalish C, de Leon D, Rutter M, Risch N, Brin M F, Markova E D, Limborska S A, Ivanova-Smolenskaya I A, McCormick M K, Fahn S, Buckler A J, Gusella J F, Breakefield X O

机构信息

Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston 02114, USA.

出版信息

Genome Res. 1997 May;7(5):483-94. doi: 10.1101/gr.7.5.483.

DOI:10.1101/gr.7.5.483

PMID:9149944

Abstract

The DYT1 gene, which maps to chromosome 9q34, appears to be responsible for most cases of early-onset torsion dystonia in both Ashkenazic Jewish (AJ) and non-Jewish families. This disease is inherited in an autosomal dominant mode with reduced penetrance (30%-40%). The abnormal involuntary movements associated with this disease are believed to be caused by unbalanced neural transmission in the basal ganglia. Previous linkage disequilibrium studies in the AJ population placed the DYT1 gene in a 2-cM region between the loci D9S62a and ASS. A YAC contig has now been created spanning 600 kb of this region including D9S62a. The location of the DYT1 gene has been refined within this contig using several new polymorphic loci to expand the linkage disequilibrium analysis of the AJ founder mutation. The most likely location of the DYT1 gene is within a 150 kb region between the loci D9S2161 and D9S63.

摘要

定位于9号染色体长臂34区的DYT1基因，似乎是阿什肯纳兹犹太（AJ）家族和非犹太家族中大多数早发性扭转性肌张力障碍病例的致病原因。这种疾病以常染色体显性模式遗传，外显率降低（30%-40%）。据信，与这种疾病相关的异常不自主运动是由基底神经节中神经传递失衡引起的。先前在AJ人群中进行的连锁不平衡研究将DYT1基因定位在D9S62a和ASS两个基因座之间2厘摩的区域内。现已构建了一个跨越该区域600千碱基对（kb）的酵母人工染色体（YAC）重叠群，其中包括D9S62a。利用几个新的多态性基因座在这个重叠群内对DYT1基因的位置进行了优化，以扩大对AJ始祖突变的连锁不平衡分析。DYT1基因最可能的位置在D9S2161和D9S63两个基因座之间150 kb的区域内。