Centre for Innovation in Agriculture, Murdoch University and C Y O'Connor ERADE Village Foundation, North Dandalup 6207, Western Australia, Australia.
Cells. 2019 Aug 21;8(9):944. doi: 10.3390/cells8090944.
Ancestral haplotypes are conserved but extremely polymorphic kilobase sequences, which have been faithfully inherited over at least hundreds of generations in spite of migration and admixture. They carry susceptibility and resistance to diverse diseases, including deficiencies of CYP21 hydroxylase (47.1) and complement components (18.1), as well as numerous autoimmune diseases (8.1). The haplotypes are detected by segregation within ethnic groups rather than by SNPs and GWAS. Susceptibility to some other diseases is carried by specific alleles shared by multiple ancestral haplotypes, e.g., ankylosing spondylitis and narcolepsy. The difference between these two types of association may explain the disappointment with many GWAS. Here we propose a pathway for combining the two different approaches. SNP typing is most useful after the conserved ancestral haplotypes have been defined by other methods.
祖先单倍型是保守但高度多态的千碱基序列，尽管存在迁移和混合，它们仍能在至少数百代中被忠实地遗传。它们携带对多种疾病的易感性和抗性，包括 CYP21 羟化酶（47.1）和补体成分（18.1）的缺乏，以及许多自身免疫性疾病（8.1）。这些单倍型是通过在族群内的分离而不是通过 SNP 和 GWAS 来检测的。一些其他疾病的易感性是由多个祖先单倍型共同携带的特定等位基因携带的，例如强直性脊柱炎和嗜睡症。这两种关联类型的区别可能解释了许多 GWAS 的失望。在这里，我们提出了一种结合这两种不同方法的途径。在通过其他方法定义了保守的祖先单倍型之后，SNP 分型是最有用的。
