Varilo T, Nikali K, Suomalainen A, Lönnqvist T, Peltonen L
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Genome Res. 1996 Sep;6(9):870-5. doi: 10.1101/gr.6.9.870.
Infantile onset spinocerebellar ataxia (IOSCA) is a progressive neurological syndrome exhibiting an autosomal recessive pattern of inheritance. The characteristic features were described in Finland in the beginning of 1990s. Having shown that IOSCA does not segregate with any of the markers linked to other hereditary ataxias and thus represents a genetically distinct disease, we assigned the locus of this new hereditary ataxia to 10q23.3-q24.1. To approximate the age of the Finnish IOSCA mutation and to investigate the possible existence of more than one mutation underlying the disease, the ancestors of 13 IOSCA families were identified by use of church records dating back to the 1500s. The IOSCA pedigrees were frequently merged, providing support for these having one common ancestor. Analysis of the extended IOSCA haplotypes exposed ancient recombination events and revealed one core haplotype of four markers on a region of approximately 2 cM, which was unequivocally present in 92% of disease chromosomes. Both genealogical and haplotype data thus suggest that a single IOSCA ancestral mutation was introduced into the Finnish population most probably approximately 30-40 generations ago before the time when the general east-west migration took place within Finland.
婴儿期起病的脊髓小脑共济失调（IOSCA）是一种呈现常染色体隐性遗传模式的进行性神经综合征。其特征在20世纪90年代初于芬兰被描述。在证明IOSCA与任何与其他遗传性共济失调相关的标记物不连锁，因此代表一种基因上不同的疾病后，我们将这种新的遗传性共济失调的基因座定位到10q23.3 - q24.1。为了估算芬兰IOSCA突变的年代，并调查该疾病是否存在一种以上的潜在突变，利用可追溯到16世纪的教会记录确定了13个IOSCA家族的祖先。IOSCA家系经常合并，这为它们有一个共同祖先提供了支持。对扩展的IOSCA单倍型的分析揭示了古老的重组事件，并在大约2厘摩的区域内发现了一个由四个标记组成的核心单倍型，在92%的疾病染色体中明确存在。因此，系谱和单倍型数据均表明，一个单一的IOSCA祖先突变最有可能在大约30 - 40代之前，即在芬兰境内普遍的东西向迁移发生之前，就被引入了芬兰人群。
