Andrew S, Theilmann J, Almqvist E, Norremolle A, Lucotte G, Anvret M, Sorensen S A, Turpin J C, Hayden M R
Department of Medical Genetics, UBC, Vancouver, Canada.
Clin Genet. 1993 Jun;43(6):286-94. doi: 10.1111/j.1399-0004.1993.tb03820.x.
Results of association studies can be significantly biased if the ancestry of the control population is not similar to that of the affected population. One approach to overcome such a bias is to use distinct populations where controls and affected individuals are likely to be of similar descent. We have examined homogeneous populations of French, Danish and Swedish ancestry for nonrandom allelic association between Huntington disease (HD) and several markers previously shown to be in association with HD. No evidence for nonrandom allelic association between HD and these markers was shown in these populations. The demonstration of association in a United Kingdom (UK) sample of similar size, and lack of significant differences in allele frequencies between the French, Danish, Swedish and UK populations suggested that the absence of association was not predominantly a consequence of allele frequencies or sample size. To investigate further the number of potential HD chromosomes, DNA haplotypes were constructed for the Danish, French, Swedish and UK populations. The minimum of two HD haplotypes observed in each of the French, Danish and Swedish populations, compared to the one haplotype in the UK population of a similar size, is an important factor accounting for the absence of association between HD and the DNA markers in these populations. Furthermore, these data are in favour of multiple independent origins for the mutation causing HD.
如果对照人群的血统与患病人群的血统不相似，关联研究的结果可能会出现显著偏差。克服这种偏差的一种方法是使用不同的人群，使对照个体和患病人个体可能具有相似的血统。我们研究了具有法国、丹麦和瑞典血统的同质人群，以寻找亨廷顿舞蹈病（HD）与先前显示与HD相关的几个标记之间的非随机等位基因关联。在这些人群中未显示HD与这些标记之间存在非随机等位基因关联。在规模相似的英国样本中显示出关联，并且法国、丹麦、瑞典和英国人群之间的等位基因频率没有显著差异，这表明无关联并非主要是等位基因频率或样本量的结果。为了进一步研究潜在HD染色体的数量，我们为丹麦、法国、瑞典和英国人群构建了DNA单倍型。在法国、丹麦和瑞典人群中每个都观察到至少两种HD单倍型，而在规模相似的英国人群中只观察到一种单倍型，这是解释这些人群中HD与DNA标记之间无关联的一个重要因素。此外，这些数据支持导致HD的突变有多个独立起源。
