Understanding the genetic causes of trait variation is a primary goal of genetic research. One way that individuals can vary genetically is through variable pangenomic genes: genes that are only present in some individuals in a population. The presence or absence of entire genes could have large effects on trait variation. However, variable pangenomic genes can be missed in standard genotyping workflows, owing to reliance on aligning short-read sequencing to reference genomes. A popular method for studying the genetic basis of trait variation is linkage mapping, which identifies quantitative trait loci (QTLs), regions of the genome that harbor causative genetic variants. Large-scale linkage mapping in the budding yeast Saccharomyces cerevisiae has found thousands of QTLs affecting myriad yeast phenotypes. To enable the resolution of QTLs caused by variable pangenomic genes, we used long-read sequencing to generate highly complete de novo genome assemblies of 16 diverse yeast isolates. With these assemblies, we resolved QTLs for growth on maltose, sucrose, raffinose, and oxidative stress to specific genes that are absent from the reference genome but present in the broader yeast population at appreciable frequency. Copies of genes also duplicate onto chromosomes where they are absent in the reference genome, and we found that these copies generate additional QTLs whose resolution requires pangenome characterization. Our findings show the need for highly complete genome assemblies to identify the genetic basis of trait variation.

中文翻译：

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高度完整的长读长基因组揭示了酵母表型多样性背后的全基因组变异


了解性状变异的遗传原因是遗传研究的首要目标。个体遗传变异的一种方式是通过可变的全基因组基因：仅存在于群体中某些个体中的基因。整个基因的存在或缺失可能对性状变异产生很大影响。然而，由于依赖短读长测序与参考基因组的比对，标准基因分型工作流程中可能会遗漏可变的全基因组基因。研究性状变异遗传基础的一种流行方法是连锁作图，它可以识别数量性状基因座（QTL），即基因组中含有致病性遗传变异的区域。芽殖酵母酿酒酵母的大规模连锁作图发现了数千个影响无数酵母表型的 QTL。为了解析由可变泛基因组基因引起的 QTL，我们使用长读长测序来生成 16 个不同酵母分离株的高度完整的从头基因组组装。通过这些组装，我们将麦芽糖、蔗糖、棉子糖和氧化应激下生长的QTL解析为特定基因，这些基因在参考基因组中不存在，但以相当高的频率存在于更广泛的酵母群体中。基因的副本也会复制到参考基因组中不存在的染色体上，我们发现这些副本会产生额外的 QTL，其分辨率需要泛基因组表征。我们的研究结果表明需要高度完整的基因组组装来确定性状变异的遗传基础。