UWA School of Agriculture and Environment, The University of Western Australia, 6009, Crawley, WA, Australia.
Helicobacter Research Laboratory, The Marshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia.
BMC Genomics. 2023 Feb 15;24(1):74. doi: 10.1186/s12864-023-09172-0.
Gastrointestinal (GIT) helminthiasis is a global problem that affects livestock health, especially in small ruminants. One of the major helminth parasites of sheep and goats, Teladorsagia circumcincta, infects the abomasum and causes production losses, reductions in weight gain, diarrhoea and, in some cases, death in young animals. Control strategies have relied heavily on the use of anthelmintic medication but, unfortunately, T. circumcincta has developed resistance, as have many helminths. Vaccination offers a sustainable and practical solution, but there is no commercially available vaccine to prevent Teladorsagiosis. The discovery of new strategies for controlling T. circumcincta, such as novel vaccine targets and drug candidates, would be greatly accelerated by the availability of better quality, chromosome-length, genome assembly because it would allow the identification of key genetic determinants of the pathophysiology of infection and host-parasite interaction. The available draft genome assembly of T. circumcincta (GCA_002352805.1) is highly fragmented and thus impedes large-scale investigations of population and functional genomics.
We have constructed a high-quality reference genome, with chromosome-length scaffolds, by purging alternative haplotypes from the existing draft genome assembly and scaffolding the result using chromosome conformation, capture-based, in situ Hi-C technique. The improved (Hi-C) assembly resulted in six chromosome-length scaffolds with length ranging from 66.6 Mbp to 49.6 Mbp, 35% fewer sequences and reduction in size. Substantial improvements were also achieved in both the values for N50 (57.1 Mbp) and L50 (5 Mbp). A higher and comparable level of genome and proteome completeness was achieved for Hi-C assembly on BUSCO parameters. The Hi-C assembly had a greater synteny and number of orthologs with a closely related nematode, Haemonchus contortus.
This improved genomic resource is suitable as a foundation for the identification of potential targets for vaccine and drug development.
胃肠道(GIT)寄生虫病是一个全球性问题,影响着牲畜的健康,尤其是在小反刍动物中。绵羊和山羊的主要寄生虫之一——圆形泰勒虫(Teladorsagia circumcincta)感染皱胃,导致生产损失、体重增加减少、腹泻,在某些情况下,幼畜会死亡。控制策略主要依赖于驱虫药物的使用,但不幸的是,圆形泰勒虫已经产生了耐药性,许多寄生虫也是如此。疫苗接种提供了一种可持续且实用的解决方案,但目前没有可商业应用的疫苗来预防泰勒虫病。如果有更好质量的染色体长度基因组组装,新的控制圆形泰勒虫的策略,如新型疫苗靶点和药物候选物的发现,将会大大加快。因为它可以识别感染病理生理学和宿主-寄生虫相互作用的关键遗传决定因素。现有的圆形泰勒虫(GCA_002352805.1)的草图基因组组装高度碎片化,因此阻碍了对种群和功能基因组学的大规模研究。
我们通过从现有草图基因组组装中剔除替代单倍型,并使用染色体构象捕获、原位 Hi-C 技术对结果进行支架构建,构建了一个具有染色体长度支架的高质量参考基因组。改进后的(Hi-C)组装得到了六个染色体长度的支架,长度从 66.6 Mbp 到 49.6 Mbp 不等,序列减少了 35%,大小减小。在 N50(57.1 Mbp)和 L50(5 Mbp)值方面也取得了实质性的提高。在 BUSCO 参数方面,Hi-C 组装的基因组和蛋白质组完整性水平更高且相当。Hi-C 组装与亲缘关系密切的线虫——捻转血矛线虫(Haemonchus contortus)的同基因和同源基因数量更多,具有更高的同基因和同源基因数量。
这个改进的基因组资源适合作为鉴定疫苗和药物开发潜在靶点的基础。