Integrative Biology, Oregon State University, Corvallis, Oregon, United States of America.
Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
PeerJ. 2022 Sep 13;10:e13971. doi: 10.7717/peerj.13971. eCollection 2022.
is a snail intermediate host for , a trematode responsible for human schistosomiasis. BS90 is one of the most well studied strains of owing to its high resistance to infection by most strains of . An F2 mapping study from 1999 identified two RAPD markers that associated with what appeared to be single-locus, dominant resistance by the BS90 population relative to the susceptible M-line population. One marker cannot be mapped, but the other, , maps to within 5 Mb of , a region we recently showed has a very large effect on resistance within another snail population challenged by the same strain of parasite (PR1). Here we tested the hypothesis that the region contains the causal gene/s that explain the iconic resistance of BS90 snails.
We used marker-assisted backcrossing to drive the BS90 version of the PTC2 region (+/-~1 Mb on either side) into an M-line (susceptible strain) genetic background, and the M-line version into a BS90 genetic background. We challenged the offspring with PR1-strain schistosomes and tested for effects of allelic variation in the region in a common genetic background.
Relative to M-line haplotypes, the BS90 haplotype actually confers enhanced susceptibility. So we reject our original hypothesis. One possible explanation for our result was that the causal gene linked to is near, but not in the block that we introgressed into each line. So we used an F2 cross to independently test the effects of the and regions in a randomized genetic background. We confirmed that the BS90 haplotype confers increased susceptibility, and we see a similar, although non-significant effect at . We discuss possible reasons why our results differed so dramatically from those of the 1999 study. We also present Pacbio assemblies of the and flanking region in BS90 and M-line, compare with previously published haplotypes, and discuss candidate genes that might be behind the enhanced susceptibility of the BS90 haplotype.
蜗牛是并殖吸虫的中间宿主,而并殖吸虫可导致人体血吸虫病。BS90 是研究最为深入的 菌株之一,因为它对大多数 菌株的感染具有高度抗性。1999 年的一项 F2 作图研究确定了两个与 BS90 群体似乎具有单基因、显性抗性相关的 RAPD 标记,而该抗性相对于易感的 M-line 群体来自于大多数 菌株的感染。其中一个标记无法进行映射,但另一个标记 映射到 以内,这是我们最近在另一个受到相同寄生虫(PR1)菌株挑战的蜗牛种群中显示对抗性具有非常大影响的区域。在这里,我们检验了以下假设,即 区域包含解释 BS90 蜗牛标志性抗性的因果基因/基因。
我们使用标记辅助回交将 BS90 版本的 PTC2 区域(两侧各约 1Mb)驱动到 M-line(易感株)遗传背景中,并将 M-line 版本驱动到 BS90 遗传背景中。我们用 PR1 株血吸虫挑战后代,并在共同遗传背景中测试 区域等位基因变异的影响。
与 M-line 单倍型相比,BS90 单倍型实际上赋予了更高的易感性。因此,我们拒绝了最初的假设。我们结果的一个可能解释是,与 相关的因果基因靠近,但不在我们引入每条线的 块中。因此,我们使用 F2 杂交在随机遗传背景中独立测试 和 区域的影响。我们证实 BS90 单倍型赋予了更高的易感性,并且我们在 中也看到了类似的、尽管不显著的效应。我们讨论了我们的结果与 1999 年研究结果如此截然不同的可能原因。我们还提供了 BS90 和 M-line 中 和侧翼区域的 Pacbio 组装,与以前发表的 单倍型进行比较,并讨论了可能导致 BS90 单倍型易感性增强的候选基因。