Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.
Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität, Munich, Germany.
BMC Biol. 2023 Nov 22;21(1):267. doi: 10.1186/s12915-023-01758-0.
The red junglefowl, the wild outgroup of domestic chickens, has historically served as a reference for genomic studies of domestic chickens. These studies have provided insight into the etiology of traits of commercial importance. However, the use of a single reference genome does not capture diversity present among modern breeds, many of which have accumulated molecular changes due to drift and selection. While reference-based resequencing is well-suited to cataloging simple variants such as single-nucleotide changes and short insertions and deletions, it is mostly inadequate to discover more complex structural variation in the genome.
We present a pangenome for the domestic chicken consisting of thirty assemblies of chickens from different breeds and research lines.
We demonstrate how this pangenome can be used to catalog structural variants present in modern breeds and untangle complex nested variation. We show that alignment of short reads from 100 diverse wild and domestic chickens to this pangenome reduces reference bias by 38%, which affects downstream genotyping results. This approach also allows for the accurate genotyping of a large and complex pair of structural variants at the K feathering locus using short reads, which would not be possible using a linear reference.
We expect that this new paradigm of genomic reference will allow better pinpointing of exact mutations responsible for specific phenotypes, which will in turn be necessary for breeding chickens that meet new sustainability criteria and are resilient to quickly evolving pathogen threats.
红原鸡是家鸡的野生外群，历史上一直被用作研究家鸡基因组学的参考。这些研究为研究具有商业重要性的性状的病因提供了思路。然而，单一参考基因组并不能捕捉到现代品种之间存在的多样性，其中许多品种由于漂变和选择而积累了分子变化。虽然基于参考的重测序非常适合对简单变体（如单核苷酸变化和短插入和缺失）进行编目，但它主要不适合发现基因组中更复杂的结构变异。
我们提出了一个家鸡的泛基因组，由来自不同品种和研究线的三十个鸡组装组成。
我们展示了如何使用这个泛基因组来编目现代品种中存在的结构变体，并理清复杂的嵌套变异。我们表明，将 100 只不同的野生和家养鸡的短读序列比对到这个泛基因组，可以减少 38%的参考偏差，这会影响下游的基因分型结果。这种方法还允许使用短读序列准确地对 K 羽区的一对大型复杂结构变体进行基因分型，而使用线性参考则不可能做到。
我们预计这种新的基因组参考范式将能够更好地确定导致特定表型的确切突变，这反过来又将是培育符合新可持续性标准且对快速进化的病原体威胁具有弹性的鸡的必要条件。
