Exceptionally long-range haplotypes in Plasmodium falciparum chromosome 6 maintained in an endemic African population.
Exceptionally long-range haplotypes in Plasmodium falciparum chromosome 6 maintained in an endemic African population.
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DOI：
10.1186/s12936-016-1560-7
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发表时间：
2016-10-21
期刊：
影响因子：
3
通讯作者：
Conway D
中科院分区：
文献类型：
--
作者：
Amambua-Ngwa A;Danso B;Worwui A;Ceesay S;Davies N;Jeffries D;D'Alessandro U;Conway D
先前对恶性疟原虫单核苷酸变异的全基因组分析发现了西非 6 号染色体上扩展单倍型区域的证据，表明最近的正选择。在东非或东南亚的样本中没有看到这种模式，因此它可能标志着西非特有的选择性过程。对不同时间采集的样本中的单倍型结构进行分析可以为选择的可能原因提供线索。本研究通过使用之前从 2008 年收集的临床分离株获得的基因组序列数据分析多个微卫星位点的等位基因，然后对 1984 年、1991 年、2008 年和 2014 年的 439 个分离株中的 13 个位点进行基因分型，研究了冈比亚的 6 号染色体扩展单倍型。确定了单倍型结构和频率的时间变化。通过 NGS 和实验室确定的微卫星等位基因，鉴定出跨越 170 kb 的高度连锁不平衡区域。在冈比亚的所有时间群体中都发现了多种长单倍型。在 1984 年和 1991 年的样本中检测到了其中两种单倍型。长程单倍型的频率在 2008 年和 2014 年人群中有所增加。在药物代谢途径相关基因附近的基因座上，较老的群体和较新的群体之间的 Fst 较高。几个长单倍型以中等频率出现表明 6 号染色体存在一种不寻常的选择模式，可能与特定单倍型的重组抑制相结合。这种选择显然发生在已知的抗疟疾药物抗性等位基因出现之前，并且可能是由于其他药物的影响或长期在该流行地区运作的未知过程造成的。本文的在线版本 (doi:10.1186/s12936-016-1560-7) 包含补充材料，可供授权用户使用。
Previous genome-wide analyses of single nucleotide variation in Plasmodium falciparum identified evidence of an extended haplotype region on chromosome 6 in West Africa, suggesting recent positive selection. Such a pattern is not seen in samples from East Africa or South East Asia, so it could be marking a selective process specific to West Africa. Analyses of the haplotype structure in samples taken at different times could give clues to possible causes of selection. This study investigates chromosome 6 extended haplotypes in The Gambia by analysing alleles at multiple microsatellite loci using genome sequence data previously obtained from clinical isolates collected in 2008, followed by genotyping of 13 loci in 439 isolates from 1984, 1991, 2008 and 2014. Temporal changes in haplotype structure and frequencies were determined. A region of high linkage disequilibrium spanning over 170 kilobases (kb) was identified with both NGS and laboratory determined microsatellite alleles. Multiple long haplotypes were found in all temporal populations from The Gambia. Two of the haplotypes were detected in samples from 1984 and 1991. The frequency of long-range haplotypes increased in 2008 and 2014 populations. There was higher Fst between older and more recent populations at loci in proximity to genes involved in drug metabolism pathways. The occurrence of several long haplotypes at intermediate frequencies suggests an unusual mode of selection in chromosome 6, possibly combined with recombination suppression on specific haplotypes. Such selection apparently occurred before the emergence of known anti-malarial drug resistance alleles, and could be due to effects of other drugs or unknown processes that have long been operating in this endemic region. The online version of this article (doi:10.1186/s12936-016-1560-7) contains supplementary material, which is available to authorized users.
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影响因子：
10.7
作者：
Mobegi VA;Duffy CW;Amambua-Ngwa A;Loua KM;Laman E;Nwakanma DC;MacInnis B;Aspeling-Jones H;Murray L;Clark TG;Kwiatkowski DP;Conway DJ
通讯作者：
Conway DJ
影响因子：
14.9
作者：
Highnam G;Franck C;Martin A;Stephens C;Puthige A;Mittelman D
通讯作者：
Mittelman D
影响因子：
5.8
作者：
Kofler, Robert;Schloetterer, Christian;Lelley, Tamas
通讯作者：
Lelley, Tamas
影响因子：
4.6
作者：
Borrmann S;Straimer J;Mwai L;Abdi A;Rippert A;Okombo J;Muriithi S;Sasi P;Kortok MM;Lowe B;Campino S;Assefa S;Auburn S;Manske M;Maslen G;Peshu N;Kwiatkowski DP;Marsh K;Nzila A;Clark TG
通讯作者：
Clark TG
影响因子：
30.8
作者：
Mu, Jianbing;Awadalla, Philip;Su, Xin-zhuan
通讯作者：
Su, Xin-zhuan