Leffler Ellen M, Band Gavin, Busby George B J, Kivinen Katja, Le Quang Si, Clarke Geraldine M, Bojang Kalifa A, Conway David J, Jallow Muminatou, Sisay-Joof Fatoumatta, Bougouma Edith C, Mangano Valentina D, Modiano David, Sirima Sodiomon B, Achidi Eric, Apinjoh Tobias O, Marsh Kevin, Ndila Carolyne M, Peshu Norbert, Williams Thomas N, Drakeley Chris, Manjurano Alphaxard, Reyburn Hugh, Riley Eleanor, Kachala David, Molyneux Malcolm, Nyirongo Vysaul, Taylor Terrie, Thornton Nicole, Tilley Louise, Grimsley Shane, Drury Eleanor, Stalker Jim, Cornelius Victoria, Hubbart Christina, Jeffreys Anna E, Rowlands Kate, Rockett Kirk A, Spencer Chris C A, Kwiatkowski Dominic P
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Science. 2017 Jun 16;356(6343). doi: 10.1126/science.aam6393. Epub 2017 May 18.
The malaria parasite invades human red blood cells by a series of interactions between host and parasite surface proteins. By analyzing genome sequence data from human populations, including 1269 individuals from sub-Saharan Africa, we identify a diverse array of large copy-number variants affecting the host invasion receptor genes and We find that a nearby association with severe malaria is explained by a complex structural rearrangement involving the loss of and gain of two hybrid genes, which encode a serologically distinct blood group antigen known as Dantu. This variant reduces the risk of severe malaria by 40% and has recently increased in frequency in parts of Kenya, yet it appears to be absent from west Africa. These findings link structural variation of red blood cell invasion receptors with natural resistance to severe malaria.
疟原虫通过宿主与寄生虫表面蛋白之间的一系列相互作用侵入人类红细胞。通过分析来自人类群体的基因组序列数据，包括1269名来自撒哈拉以南非洲的个体，我们识别出一系列影响宿主入侵受体基因的大量拷贝数变异。我们发现，与严重疟疾的附近关联是由一种复杂的结构重排所解释的，该重排涉及两个杂交基因的缺失和获得，这两个杂交基因编码一种血清学上不同的血型抗原，称为丹图。这种变异使严重疟疾的风险降低了40%，并且最近在肯尼亚部分地区的频率有所增加，但在西非似乎不存在。这些发现将红细胞入侵受体的结构变异与对严重疟疾的天然抗性联系起来。
