A gene for autosomal dominant juvenile amyotrophic lateral sclerosis (ALS4) localizes to a 500-kb interval on chromosome 9q34.
A gene for autosomal dominant juvenile amyotrophic lateral sclerosis (ALS4) localizes to a 500-kb interval on chromosome 9q34.
复制标题
常染色体显性青少年肌萎缩侧索硬化症 (ALS4) 基因定位于染色体 9q34 上 500 kb 的间隔。
DOI：
10.1007/pl00022976
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发表时间：
2000
期刊：
影响因子：
2.2
通讯作者：
Chance,PF
中科院分区：
文献类型：
--
作者：
Blair,IP;Bennett,CL;Abel,A;Rabin,BA;Griffin,JW;Fischbeck,KH;Cornblath,DR;Chance,PF
肌萎缩侧索硬化症（ALS）是一组影响上下运动神经元的神经退行性疾病。ALS 4是一种幼年发病的常染色体显性形式的ALS，其特征在于进展缓慢、远端肢体无力和肌萎缩以及与脑和脊髓中运动神经元的严重丧失相关的锥体束征。的 ALS4 最近通过连锁分析将一个基因座定位在染色体9 q34上的一个大的遗传区间上。通过进行广泛的遗传连锁分析，我们已经大大改善了 ALS4 基因座的临界间隔小于3 cM，两侧是D9 S149和D9 S1198。以前在这一地区的物理映射表明，这一关键间隔跨越约500 kb。17个假定的转录本已经定位在这个区间内，包括7个特征基因，2个部分特征基因，和8个“匿名”表达序列标签。因此，这些基因是用于基因治疗的位置候选基因。 ALS4 基因座我们还进行了突变分析和遗传图谱研究，以排除候选基因，包括 RING3L/ORFX 和 RALGDS ，从ALS 4的致病作用。
Amyotrophic lateral sclerosis (ALS) denotes a heterogeneous group of neurodegenerative disorders affecting upper and lower motor neurons. ALS4 is a juvenile-onset, autosomal dominant form of ALS that is characterized by slow progression, distal limb weakness and amyotrophy, and pyramidal signs associated with severe loss of motor neurons in the brain and spinal cord. The ALS4 locus was recently mapped by linkage analysis to a large genetic interval on chromosome 9q34. By undertaking extensive genetic linkage analysis, we have significantly refined the ALS4 locus to a critical interval of less than 3 cM, flanked by D9S149 and D9S1198. Previous physical mapping in this region has indicated that this critical interval spans approximately 500 kb. Seventeen putative transcripts have been localized within this interval including 7 characterized genes, 2 partially characterized genes, and 8 "anonymous" expressed sequence tags . These are therefore positional candidate genes for the ALS4 locus. We have also undertaken mutation analysis and genetic mapping to investigate and exclude candidate genes, including RING3L/ORFX and RALGDS , from a pathogenic role in ALS4.