Structural variation in the human genome can affect risk of disease. An example is a complex structural variant of the human glycophorin gene cluster, called DUP4, which is associated with a clinically significant level of protection against severe malaria. The human glycophorin gene cluster harbours at least 23 distinct structural variants, and accurate genotyping of this complex structural variation remains a challenge. Here, we use a polymerase chain reaction‐based strategy to genotype structural variation at the human glycophorin gene cluster, including the alleles responsible for the U– blood group. We validate our approach, based on a triplex paralogue ratio test, on publically available samples from the 1000 Genomes project. We then genotype 574 individuals from a longitudinal birth cohort (Tori‐Bossito cohort) using small amounts of DNA at low cost. Our approach readily identifies known deletions and duplications, and can potentially identify novel variants for further analysis. It will allow exploration of genetic variation at the glycophorin locus, and investigation of its relationship with malaria, in large sample sets at minimal cost, using standard molecular biology equipment.

中文翻译：

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使用基于 PCR 的策略对疟疾相关人血型糖蛋白基因座的复杂结构变异进行基因分型

人类基因组的结构变异会影响疾病风险。一个例子是人类血型糖蛋白基因簇的复杂结构变体，称为 DUP4，它与临床上显着的严重疟疾保护水平相关。人类血型糖蛋白基因簇包含至少 23 个不同的结构变异，对这种复杂结构变异的准确基因分型仍然是一个挑战。在这里，我们使用基于聚合酶链反应的策略对人类血型糖蛋白基因簇的结构变异进行基因分型，包括负责 U- 血型的等位基因。我们基于三重旁系同源比测试，对来自 1000 Genomes 项目的公开样本验证了我们的方法。然后，我们使用少量 DNA 以低成本对来自纵向出生队列（Tori-Bossito 队列）的 574 个人进行基因分型。我们的方法很容易识别已知的缺失和重复，并且可以潜在地识别新的变异以供进一步分析。它将允许使用标准分子生物学设备以最低成本在大样本集中探索血型糖蛋白基因座的遗传变异，并调查其与疟疾的关系。