A linkage disequilibrium at the candidate gene locus for 16q-linked autosomal dominant cerebellar ataxia type III in Japan
A linkage disequilibrium at the candidate gene locus for 16q-linked autosomal dominant cerebellar ataxia type III in Japan
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DOI：
10.1007/s100380170083
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发表时间：
2001-01-01
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：
Takashima, M;Ishikawa, K;Mizusawa, H
我们之前将负责常染色体显性小脑共济失调 (ADCA) III 型的基因定位到染色体 16q 上 D16S3089 和 D16S515 之间 10.9 cM 的间隔。然而，该区域与 4 型脊髓小脑共济失调 (SCA4) 的候选位点相同。在这项研究中，我们通过应用 20 个微卫星 DNA 标记的连锁不平衡来扩展我们的研究，以细化疾病的基因位点。通过 D16S3031 和 D16S3107 两侧的 9 个标记，我们发现 6 个家系的受影响个体在其疾病染色体上具有共同的单倍型。此外，5 个信息性标记证明了连锁不平衡：D16S3019 (P = 0.013)、D16S3067 (P = 0.008)、D16S3141(P = 0.011)、D16S496 (P = 0.032) 和 D16S3107 (P = 0.000)。这些结果表明，该疾病可能起源于在 D16S3043 和 D16S3095 之间小于 3 cM 的区域内含有突变的共同祖先。在与这六个家族无关的其他 ADCA III 型患者中也观察到了创始人等位基因。
We previously mapped the gene responsible for autosomal dominant cerebellar ataxia (ADCA) type III to a 10.9-cM interval between D16S3089 and D16S515 on chromosome 16q. This region, however, was identical to the candidate locus of spinocerebellar ataxia type 4 (SCA4). In this study, we extended our research to refine the gene locus of the disease by applying linkage disequilibrium with 20 microsatellite DNA markers. With 9 markers flanked by D16S3031 and D16S3107, we found that the affected individuals in six families had a common haplotype on their disease chromosomes. Furthermore, linkage disequilibrium was demonstrated with 5 informative markers: D16S3019 (P = 0.013), D16S3067 (P = 0.008), D16S3141(P = 0.011), D16S496 (P = 0.032), and D16S3107 (P = 0.000). These results indicate that the disease could have originated from a common ancestor harboring a mutation within a less than 3-cM region between D16S3043 and D16S3095. The founder alleles were also observed in other patients with ADCA type III unrelated to the six families.