Assembly of the genome of the disease vector Aedes aegypti onto a genetic linkage map allows mapping of genes affecting disease transmission.

Assembly of the genome of the disease vector Aedes aegypti onto a genetic linkage map allows mapping of genes affecting disease transmission.
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DOI:
10.1371/journal.pntd.0002652
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发表时间:
2014
影响因子:
3.8
通讯作者:
Jiggins FM
Jiggins FM
中科院分区:
医学2区
文献类型:
--
作者:
Juneja P;Osei-Poku J;Ho YS;Ariani CV;Palmer WJ;Pain A;Jiggins FM

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埃及伊蚊传播一些最重要的人类虫媒病毒,包括登革热、黄热病和基孔肯雅病毒。它的基因组很大,包含许多重复序列,这导致基因组的组装很差——有 4,758 个支架,其中很少有被分配到染色体上的。为了绘制影响疾病传播的基因图谱,我们通过对两种伊蚊菌株杂交的重组后代中的大量 SNP 进行评分,改进了基因组组装。埃及伊蚊,并使用它们生成遗传图谱。这揭示了当前基因组中的高错误组装率,例如,在同一支架上发现了来自不同染色体的序列。一旦这些得到纠正,我们就能够将 60% 的基因组序列分配给染色体,并沿着染色体大致排列支架。我们发现着丝粒周围有非常大的重组抑制区域,可以延伸到染色体的 47%。为了说明这种新基因组组装的实用性,我们绘制了一个产生 Ae 的基因。埃及伊蚊对人类寄生虫马来丝虫具有抗性,并生成了可能影响该性状的候选基因列表。蚊子对于传播登革热和黄热病等人类疾病非常重要。对包括埃及伊蚊在内的主要蚊子物种的基因组测序帮助我们了解了蚊子传播疾病的因素。而Ae的基因组。埃及伊蚊已被测序,它的许多片段尚未在染色体上排列。为此,我们创建了遗传连锁图并测量了遗传标记之间的距离,这使我们能够将它们分配到基因组的区域。使用这种方法,我们还检测到当前基因组序列中的错误。我们利用基因图谱找到了与马来丝虫发育相关的蚊子基因组区域,马来丝虫是一种导致人类淋巴丝虫病的线虫。更好的基因组组装对于开发控制疾病传播的新方法非常重要。
The mosquito Aedes aegypti transmits some of the most important human arboviruses, including dengue, yellow fever and chikungunya viruses. It has a large genome containing many repetitive sequences, which has resulted in the genome being poorly assembled — there are 4,758 scaffolds, few of which have been assigned to a chromosome. To allow the mapping of genes affecting disease transmission, we have improved the genome assembly by scoring a large number of SNPs in recombinant progeny from a cross between two strains of Ae. aegypti, and used these to generate a genetic map. This revealed a high rate of misassemblies in the current genome, where, for example, sequences from different chromosomes were found on the same scaffold. Once these were corrected, we were able to assign 60% of the genome sequence to chromosomes and approximately order the scaffolds along the chromosome. We found that there are very large regions of suppressed recombination around the centromeres, which can extend to as much as 47% of the chromosome. To illustrate the utility of this new genome assembly, we mapped a gene that makes Ae. aegypti resistant to the human parasite Brugia malayi, and generated a list of candidate genes that could be affecting the trait. Mosquitoes are important for transmission of human diseases including dengue and yellow fever. The sequencing of the genomes of key mosquito species including Aedes aegypti has helped us to understand the factors that allow mosquitoes to vector disease. While the genome for Ae. aegypti has been sequenced, it is in many pieces which have not yet been arranged on chromosomes. To this end, we have created a genetic linkage map and measured the distance between genetic markers, which allows us to assign them to regions of the genome. Using this method, we also detected errors in the current genome sequences. We used our genetic map to find regions of the mosquito genome associated with the development of Brugia malayi, a nematode that causes lymphatic filariasis in humans. A better genome assembly will be important for the development of novel methods for controlling disease transmission.
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