High-density linkage map to find snail genes that block schistosome transmission

高密度连锁图谱寻找阻止血吸虫传播的蜗牛基因

• 批准号: 8960339
• 负责人: Michael Scott Blouin
• 金额: $ 14.6万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-11-01 至 2017-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8960339
• 关键词: Binding; Biochemical; Biomphalaria; Candidate Disease Gene; Chromosome Mapping; Chromosomes; Chronic; Chronic Disease; Communities; Complement; Country; Culicidae; DNA; Development; Disease; Dose; Drug resistance; Elements; Epidemiology; Evolution; Foundations; Genes; Genetic Markers; Genetic Variation; Genome; Genomic Segment; Genomics; Goals; Health; Helminths; Human; Immune response; Immune system; Immunity; Infection; Link; Malaria; Maps; Methods; Modeling; Molecular; Outcome; Parasites; Parasitic Diseases; Pharmaceutical Preparations; Phenotype; Plasmodium; Population; Population Genetics; Praziquantel; Research; Research Personnel; Resistance; Resources; Schistosoma; Schistosomatidae; Schistosomiasis; Snails; Staging; System; Therapeutic; Vaccines; Variant; Water; Work; base; density; design; disability; disability-adjusted life years; effective therapy; functional genomics; gene discovery; genome sequencing; genome wide association study; immune function; innovation; interest; novel strategies; reference genome; resistance gene; study population; success; therapeutic target; trait; transmission process

DESCRIPTION (provided by applicant): Schistosomiasis is by far the most important helminth parasitic disease of humans. Vaccines are unavailable, the only effective treatment involves repeated dosing with a single drug (praziquantel), and now drug resistance is a concern. Schistosomes are transmitted by aquatic snails. Understanding the molecular mechanisms by which snails and schistosomes interact is key for new strategies to interrupt transmission. To this end, the genome of the snail Biomphalaria glabrata was recently sequenced. However, because >50% of the 0.9 Gb genome is highly repetitive, it remains very poorly assembled. It consists of >500,000 contigs, with half the genome contained on contigs under 43 kb (N50 = about the size of a gene). As a result, any genetic markers that associate with parasite immunity are unlikely to be found on the same contig as the causal gene to which they are linked. Six markers linked to schistosome resistance are known in B. glabrata. But most of the genes linked to those markers remain a mystery owing to the inadequate genome assembly. Thus, one of the most important goals of the Biomphalaria research community, to find genes associated with immunity, is currently severely hampered. Fortunately, there is an alternative to complete genome assembly. The repetitive portion of the genome is of little epidemiological importance because we expect it to contain few functional elements or useful genetic markers. The non-repetitive regions of the genome, which include the vast majority of genes, can be assembled with a high-density linkage map via the powerful new method of targeted sequence capture. We are uniquely poised to develop this map, given our preliminary work with linkage mapping in B. glabrata and our past success with high-density targeted capture in other systems. The specific objectives of this application are (1) to generate a high-density linkage map of the non-repetitive fraction of the B. glabrata genome, and then (2) use that map to identify genes surrounding resistance markers. This map will employ ~40,000 genetic markers to unite >99% of the unique genomic sequence, including >95% of genes, into large linkage groups corresponding to the 18 snail chromosomes. Innovation: Targeted capture is a new approach that has never been used with Biomphalaria. Focusing on just the single-copy, gene-containing fraction of the genome sidesteps the challenge of assembling such a repetitive genome, while creating a high-quality genomic resource for trait mapping. This approach should also be a model for other poorly-assembled genomes. Significance: The snail genome project has thus far failed to facilitate trait mapping as expected. This linkage map will remove the last barrier to rapidly identifying genes that control snail immunity and other phenotypic traits. Understanding snail immunity will reveal new ways to potentially interfere with the parasite (e.g. therapeutics targeting parasite molecules that are targeted by the snail immune system) or to manipulate snail populations to make them into less competent hosts.

描述（由申请人提供）：血吸虫病是迄今为止人类最重要的寄生虫病。没有疫苗，唯一有效的治疗方法是反复服用单一药物（吡喹酮），现在耐药性是一个问题。血吸虫是由水生蜗牛传播的。了解蜗牛和血吸虫相互作用的分子机制是阻断传播的新策略的关键。为此，最近对蜗牛光螺（Biomphalaria glabrata）基因组进行了测序。然而，由于0.9 Gb的基因组中有50%是高度重复的，因此它的组装仍然很差。它由50万个contigs组成，其中一半的基因组包含在43 kb （N50 =大约一个基因的大小）以下的contigs上。因此，任何与寄生虫免疫相关的遗传标记都不太可能在与其相关的致病基因相同的基因上找到。已知有6种标记与光斑田鼠的血吸虫抗性有关。但由于基因组组装不足，与这些标记相关的大多数基因仍然是一个谜。因此，生物phalaria研究界最重要的目标之一，即寻找与免疫相关的基因，目前受到严重阻碍。幸运的是，有一种替代完整基因组组装的方法。基因组的重复部分在流行病学上的重要性不大，因为我们认为它包含很少的功能元素或有用的遗传标记。基因组的非重复区域，包括绝大多数基因，可以通过强大的靶向序列捕获的新方法与高密度的连锁图谱组装。考虑到我们在白僵菌中的连锁图谱的初步工作，以及我们过去在其他系统中高密度靶向捕获的成功，我们有独特的条件来开发这张地图。该应用程序的具体目标是(1)生成非重复序列的高密度链接图

项目成果

Allelic variation partially regulates galactose-dependent hydrogen peroxide release from circulating hemocytes of the snail Biomphalaria glabrata.

• DOI: 10.1016/j.fsi.2017.10.037
• 发表时间: 2018-01
• 期刊: Fish & shellfish immunology
• 影响因子: 4.7
• 作者: Allan ERO;Blouin MS
• 通讯作者: Blouin MS

A Targeted Capture Linkage Map Anchors the Genome of the Schistosomiasis Vector Snail, Biomphalaria glabrata.

• DOI: 10.1534/g3.117.041319
• 发表时间: 2017-07-05
• 期刊: G3 (Bethesda, Md.)
• 作者: Tennessen JA;Bollmann SR;Blouin MS
• 通讯作者: Blouin MS