Instituto de Pesquisa René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
PLoS Genet. 2019 Mar 8;15(3):e1008027. doi: 10.1371/journal.pgen.1008027. eCollection 2019 Mar.
Populations in sub-Saharan Africa have historically been exposed to intense selection from chronic infection with falciparum malaria. Interestingly, populations with the highest malaria intensity can be identified by the increased occurrence of endemic Burkitt Lymphoma (eBL), a pediatric cancer that affects populations with intense malaria exposure, in the so called "eBL belt" in sub-Saharan Africa. However, the effects of intense malaria exposure and sub-Saharan populations' genetic histories remain poorly explored. To determine if historical migrations and intense malaria exposure have shaped the genetic composition of the eBL belt populations, we genotyped ~4.3 million SNPs in 1,708 individuals from Ghana and Northern Uganda, located on opposite sides of eBL belt and with ≥ 7 months/year of intense malaria exposure and published evidence of high incidence of BL. Among 35 Ghanaian tribes, we showed a predominantly West-Central African ancestry and genomic footprints of gene flow from Gambian and East African populations. In Uganda, the North West population showed a predominantly Nilotic ancestry, and the North Central population was a mixture of Nilotic and Southern Bantu ancestry, while the Southwest Ugandan population showed a predominant Southern Bantu ancestry. Our results support the hypothesis of diverse ancestral origins of the Ugandan, Kenyan and Tanzanian Great Lakes African populations, reflecting a confluence of Nilotic, Cushitic and Bantu migrations in the last 3000 years. Natural selection analyses suggest, for the first time, a strong positive selection signal in the ATP2B4 gene (rs10900588) in Northern Ugandan populations. These findings provide important baseline genomic data to facilitate disease association studies, including of eBL, in eBL belt populations.
撒哈拉以南非洲的人群历史上一直受到恶性疟原虫慢性感染的强烈选择。有趣的是，疟疾强度最高的人群可以通过在所谓的“eBL 带”中发现地方性 Burkitt 淋巴瘤（eBL）的高发来识别，这是一种影响疟疾暴露强烈的人群的儿科癌症。然而，强烈的疟疾暴露和撒哈拉以南人群的遗传史的影响仍未得到充分探索。为了确定历史迁徙和强烈的疟疾暴露是否塑造了 eBL 带人群的遗传组成，我们对加纳和乌干达北部的 1708 个人进行了约 430 万个 SNP 的基因分型，这些个体位于 eBL 带的两侧，每年有≥7 个月的强烈疟疾暴露，并且有 BL 高发的证据。在 35 个加纳部落中，我们显示出主要是西非和中非的祖先，并显示出来自冈比亚和东非人群的基因流动的基因组足迹。在乌干达，西北人口显示出主要是尼罗特人的祖先，而中北部人口是尼罗特人和南部班图人的混合祖先，而西南部乌干达人口则显示出主要是南部班图人的祖先。我们的结果支持了乌干达、肯尼亚和坦桑尼亚大湖非洲人群的多种祖先起源的假设，反映了在过去 3000 年中，尼罗特人、库希特人和班图人迁徙的融合。自然选择分析首次表明，乌干达北部人群中 ATP2B4 基因（rs10900588）存在强烈的阳性选择信号。这些发现为在 eBL 带人群中进行疾病关联研究，包括 eBL，提供了重要的基线基因组数据。
