Physical map and haplotype analysis of 16q-linked autosomal dominant cerebellar ataxia (ADCA) type III in Japan
Physical map and haplotype analysis of 16q-linked autosomal dominant cerebellar ataxia (ADCA) type III in Japan
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DOI：
10.1007/s100380300017
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发表时间：
2003-01-01
影响因子：
3.5
通讯作者：
Mizusawa, H
中科院分区：
文献类型：
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作者：
Li, M;Ishikawa, K;Mizusawa, H
常染色体显性小脑性共济失调（ADCA）是一组异质性神经退行性疾病。我们之前将患有纯小脑综合征（ADCA III 型）的 ADCA 基因位点映射到染色体 16q 的 3-cM 区域，并在受影响的个体中发现了常见的单倍型。该区域恰好位于另一种 ADCA——脊髓小脑共济失调 4 型（SCA4）的位点内。为了鉴定导致 16q 连锁 ADCA 111 型的基因，我们在 D16S3043 和 D16S3095 之间构建了具有 38 个细菌人工染色体克隆的重叠群。该重叠群的大小估计为 4.8Mb。我们在这个候选区域发现了超过 500 个核苷酸串联重复，包括 9 个 CAG/CTG 重复，尽管分析的 94 个串联重复均没有在受影响的个体中扩展。然而，我们发现了 11 个新的多态性标记，从而提供了跨越候选区域的 22 个标记。通过在 ADCA III 型的 8 个日本家族（包括两个新家族）上对这些标记进行分型，我们发现在更受限的 3.8 Mb 区域中可以看到常见的“创始人”单倍型，跨越标记 GGAA05 和 D16S3095。我们在此提出了新改进的 16q-ADCA III 型/SCA4 临界区间。 16q22.1 上 11 个新 DNA 标记的数据也可用于定位到该区域的基因的其他研究。
Autosomal dominant cerebellar ataxia (ADCA) is a group of heterogeneous neurodegenerative disorders. We previously mapped a gene locus for ADCA with pure cerebellar syndrome (ADCA type III) to a 3-cM region in chromosome 16q, and found a common haplotype among affected individuals. This region was exactly within the locus for another ADCA, spinocerebellar ataxia type 4 (SCA4). To identify the gene causing 16q-linked ADCA type 111, we constructed a contig with 38 bacterial artificial chromosome clones between D16S3043 and D16S3095. The size of this contig was estimated to be 4.8Mb. We found more than 500 nucleotide tandem repeats, including 9 CAG/CTG repeats in this candidate region, although none of the 94 tandem repeats analyzed were expanded in affected individuals. However, we found 11 new polymorphic markers, giving 22 markers spanning the candidate region. By typing these markers on eight Japanese families with ADCA type III, including two new families, we found that a common "founder" haplotype is seen in a more restricted 3.8-Mb region, spanning markers GGAA05 and D16S3095. We present here a newly refined critical interval of 16q-ADCA type III/SCA4. Data of 11 new DNA markers on 16q22.1 would also be useful for other research of genes mapped to this region.