Genome-Wide Scan and Test of Candidate Genes in the Snail Biomphalaria glabrata Reveal New Locus Influencing Resistance to Schistosoma mansoni.
Genome-Wide Scan and Test of Candidate Genes in the Snail Biomphalaria glabrata Reveal New Locus Influencing Resistance to Schistosoma mansoni.
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DOI：
10.1371/journal.pntd.0004077
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发表时间：
2015
影响因子：
3.8
通讯作者：
Blouin MS
中科院分区：
文献类型：
--
作者：
Tennessen JA;Bonner KM;Bollmann SR;Johnstun JA;Yeh JY;Marine M;Tavalire HF;Bayne CJ;Blouin MS
通过提高对专性钉螺宿主抵抗血吸虫寄生虫机制的了解，可以揭示抗击全球血吸虫病祸害的新战略。然而，在钉螺中几乎没有发现与抗性相关的分子标记。在这里，我们测试了6个独立的遗传基因座，它们对曼氏血吸虫PR1株的抗性的影响，在13-16-R1品系的钉螺光滑。我们首先在1611个信息性的限制性位点相关DNA(RAD)标记中确定了一个基因组区域RADres，该区域显示了感病和抗病近交系之间的最高分化，并表明它显著影响了独立的439只近交钉螺的抗性。每个RADres抗性等位基因的加性效应为2倍，与先前发现的抗性基因SOD1的加性效应相似。这些数据符合一个模型，在该模型中，两个基因座对抗性独立和相加地起作用，因此两个基因座的抗性等位基因在纯合子中感染的几率(13%感染)比没有任何抗性等位基因的钉螺感染几率(70%)低16倍。全基因组的连锁不平衡很高，SOD1和RADRES都位于单倍型区块>；2Mb上，每个区块上的其他标记也显示出显著的抗性效应；因此，这些区块内的致病基因仍有待证实。其他候选基因对抗性没有影响，包括瓜德罗普抗性复合体和三个具有免疫学作用和与抗性相关的表达模式的基因(AIF、InfPhox和PrX1)，因此必须进行反式调控。RADRES和SOD1两个基因座对曼氏假单胞菌的抗性均有较强的影响。今后控制血吸虫病的方法可能会受益于进一步确定和利用这种自然遗传变异的努力。水生蜗牛传播血吸虫，导致一种对全球健康影响仅次于疟疾的寄生虫病。一些蜗牛天然抵抗感染的机制还知之甚少，但如果具有特征性，可能会使方案能够干扰疾病的传播。在这里，我们确定了蜗牛基因组中与感染抵抗力相关的一个区域，并与先前描述的抵抗力基因一起研究了它对免疫的影响。在这个实验室群体中，其他候选基因的变异对寄生虫的抵抗力没有影响。这两个抗药性区域可以作为靶点，阻止寄生虫通过蜗牛传播。
New strategies to combat the global scourge of schistosomiasis may be revealed by increased understanding of the mechanisms by which the obligate snail host can resist the schistosome parasite. However, few molecular markers linked to resistance have been identified and characterized in snails. Here we test six independent genetic loci for their influence on resistance to Schistosoma mansoni strain PR1 in the 13-16-R1 strain of the snail Biomphalaria glabrata. We first identify a genomic region, RADres, showing the highest differentiation between susceptible and resistant inbred lines among 1611 informative restriction-site associated DNA (RAD) markers, and show that it significantly influences resistance in an independent set of 439 outbred snails. The additive effect of each RADres resistance allele is 2-fold, similar to that of the previously identified resistance gene sod1. The data fit a model in which both loci contribute independently and additively to resistance, such that the odds of infection in homozygotes for the resistance alleles at both loci (13% infected) is 16-fold lower than the odds of infection in snails without any resistance alleles (70% infected). Genome-wide linkage disequilibrium is high, with both sod1 and RADres residing on haplotype blocks >2Mb, and with other markers in each block also showing significant effects on resistance; thus the causal genes within these blocks remain to be demonstrated. Other candidate loci had no effect on resistance, including the Guadeloupe Resistance Complex and three genes (aif, infPhox, and prx1) with immunological roles and expression patterns tied to resistance, which must therefore be trans-regulated. The loci RADres and sod1 both have strong effects on resistance to S. mansoni. Future approaches to control schistosomiasis may benefit from further efforts to characterize and harness this natural genetic variation. Aquatic snails transmit schistosome blood flukes, causing a parasitic disease second only to malaria in its global health impact. The mechanisms by which some snails naturally resist infection are poorly understood, but if characterized could enable protocols to interfere with transmission of the disease. Here we identify a region of the snail genome that correlates with resistance to infection, and we examine its effect on immunity jointly with a previously described resistance gene. Variation at other candidate genes has no effect on parasite resistance in this laboratory population. The two resistance regions could serve as targets to block parasite transmission via snails.