Apolipoprotein L1 (APOL1) risk variant toxicity depends on the haplotype background
Apolipoprotein L1 (APOL1) risk variant toxicity depends on the haplotype background
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DOI：
10.1016/j.kint.2019.07.010
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发表时间：
2019-12-01
影响因子：
19.6
通讯作者：
Friedman, David J.
中科院分区：
文献类型：
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作者：
Lannon, Herbert;Shah, Shrijal S.;Friedman, David J.
在遗传学研究中，载脂蛋白L1(APOL1)风险变异体G1和G2与非裔美国人肾脏疾病的高发病率有关。然而，我们对APOL1生物学的了解却远远落后。在这里，我们报告了在非自然的单倍型背景上而不是在自然界中发生的特定的G1和G2单倍型背景上工程G1和G2突变深刻地改变了实验系统中APOL1介导的细胞毒性。因此，除了帮助解决APOL1领域的一些重要争议外，我们对单倍型背景的关键影响的论证可能更广泛地适用于导致或易患人类疾病的其他遗传变异的研究。
The Apolipoprotein L1 (APOL1) risk variants G1 and G2 are associated with high rates of kidney disease in African Americans in genetic studies. However, our understanding of APOL1 biology has lagged far behind. Here we report that engineering G1 and G2 mutations on unnatural haplotype backgrounds instead of on the specific G1 and G2 haplotype backgrounds that occur in nature profoundly alters APOL1-mediated cytotoxicity in experimental systems. Thus, in addition to helping resolve some important controversies in the APOL1 field, our demonstration of the critical influence of haplotype background may apply more generally to the study of other genetic variants that cause or predispose to human disease.