Tang Juliet D, Perkins Andy, Williams W Paul, Warburton Marilyn L
USDA FS Forest Products Laboratory, Durability and Wood Protection, Starkville, MS, 39759, USA.
Computer Science and Engineering, Mississippi State, MS, 39762, USA.
BMC Genomics. 2015 Sep 3;16(1):673. doi: 10.1186/s12864-015-1874-9.
Aflatoxin is a potent carcinogen that can contaminate grain infected with the fungus Aspergillus flavus. However, resistance to aflatoxin accumulation in maize is a complex trait with low heritability. Here, two complementary analyses were performed to better understand the mechanisms involved. The first coupled results of a genome-wide association study (GWAS) that accounted for linkage disequilibrium among single nucleotide polymorphisms (SNPs) with gene-set enrichment for a pathway-based approach. The rationale was that the cumulative effects of genes in a pathway would give insight into genetic differences that distinguish resistant from susceptible lines of maize. The second involved finding non-pathway genes close to the most significant SNP-trait associations with the greatest effect on reducing aflatoxin in multiple environments. Unlike conventional GWAS, the latter analysis emphasized multiple aspects of SNP-trait associations rather than just significance and was performed because of the high genotype x environment variability exhibited by this trait.
The most significant metabolic pathway identified was jasmonic acid (JA) biosynthesis. Specifically, there was at least one allelic variant for each step in the JA biosynthesis pathway that conferred an incremental decrease to the level of aflatoxin observed among the inbred lines in the GWAS panel. Several non-pathway genes were also consistently associated with lowered aflatoxin levels. Those with predicted functions related to defense were: leucine-rich repeat protein kinase, expansin B3, reversion-to-ethylene sensitivity1, adaptor protein complex2, and a multidrug and toxic compound extrusion protein.
Our genetic analysis provided strong evidence for several genes that were associated with aflatoxin resistance. Inbred lines that exhibited lower levels of aflatoxin accumulation tended to share similar haplotypes for genes specifically in the pathway of JA biosynthesis, along with several non-pathway genes with putative defense-related functions. Knowledge gained from these two complementary analyses has improved our understanding of population differences in aflatoxin resistance.
黄曲霉毒素是一种强效致癌物，可污染被黄曲霉菌感染的谷物。然而，玉米对黄曲霉毒素积累的抗性是一个复杂性状，遗传力较低。在此，进行了两项互补分析以更好地理解其中涉及的机制。第一项分析将考虑单核苷酸多态性（SNP）之间连锁不平衡的全基因组关联研究（GWAS）结果与基于通路的方法的基因集富集分析相结合。其基本原理是，通路中基因的累积效应将有助于深入了解区分玉米抗性和敏感品系的遗传差异。第二项分析涉及找到与多个环境中对降低黄曲霉毒素影响最大的最显著SNP-性状关联附近的非通路基因。与传统GWAS不同，后一项分析强调SNP-性状关联的多个方面而非仅仅是显著性，并且由于该性状表现出的高基因型×环境变异性而进行。
鉴定出的最显著代谢通路是茉莉酸（JA）生物合成。具体而言，JA生物合成通路中的每个步骤都至少有一个等位基因变体，其导致GWAS群体中近交系间观察到的黄曲霉毒素水平逐渐降低。几个非通路基因也始终与较低的黄曲霉毒素水平相关。那些具有预测防御相关功能的基因是：富含亮氨酸重复蛋白激酶、扩张蛋白B3、乙烯敏感性恢复1、衔接蛋白复合体2和一种多药及有毒化合物外排蛋白。
我们的遗传分析为几个与黄曲霉毒素抗性相关的基因提供了有力证据。黄曲霉毒素积累水平较低的近交系往往在JA生物合成通路中的基因以及几个具有假定防御相关功能的非通路基因上共享相似的单倍型。从这两项互补分析中获得的知识增进了我们对黄曲霉毒素抗性群体差异的理解。
