Genome Center, MIND Institute, and Department of Biochemistry & Molecular Medicine, Davis, CA 95616, USA.
Integrative Genetics and Genomics Graduate Group, University of California, Davis, CA 95616, USA.
Genes (Basel). 2020 Mar 4;11(3):276. doi: 10.3390/genes11030276.
Recent efforts to comprehensively characterize great ape genetic diversity using short-read sequencing and single-nucleotide variants have led to important discoveries related to selection within species, demographic history, and lineage-specific traits. Structural variants (SVs), including deletions and inversions, comprise a larger proportion of genetic differences between and within species, making them an important yet understudied source of trait divergence. Here, we used a combination of long-read and -range sequencing approaches to characterize the structural variant landscape of two additional individuals, one of whom carries 13% admixture from . We performed optical mapping of both individuals followed by nanopore sequencing of one individual. Filtering for larger variants (>10 kbp) and combined with genotyping of SVs using short-read data from the Great Ape Genome Project, we identified 425 deletions and 59 inversions, of which 88 and 36, respectively, were novel. Compared with gene expression in humans, we found a significant enrichment of chimpanzee genes with differential expression in lymphoblastoid cell lines and induced pluripotent stem cells, both within deletions and near inversion breakpoints. We examined chromatin-conformation maps from human and chimpanzee using these same cell types and observed alterations in genomic interactions at SV breakpoints. Finally, we focused on 56 genes impacted by SVs in >90% of chimpanzees and absent in humans and gorillas, which may contribute to chimpanzee-specific features. Sequencing a greater set of individuals from diverse subspecies will be critical to establish the complete landscape of genetic variation in chimpanzees.
最近，人们利用短读测序和单核苷酸变体，全面描述了大型猿类的遗传多样性，这使得人们对物种内的选择、种群历史和谱系特异性特征有了重要的发现。结构变体（SVs），包括缺失和倒位，在物种之间和内部的遗传差异中占更大的比例，因此它们是一个重要但研究不足的性状分歧来源。在这里，我们使用长读和长范围测序方法，对另外两个个体的结构变体景观进行了描述，其中一个个体携带了 13%来自 的混合血统。我们对两个个体都进行了光学作图，然后对一个个体进行了纳米孔测序。过滤掉>10 kbp 的较大变体，并结合使用来自大猿基因组计划的短读数据进行 SV 基因分型，我们鉴定出 425 个缺失和 59 个倒位，其中分别有 88 个和 36 个是新的。与人类的基因表达相比，我们发现了在淋巴母细胞系和诱导多能干细胞中差异表达的黑猩猩基因的显著富集，无论是在缺失中还是在倒位断点附近。我们使用相同的细胞类型检查了来自人类和黑猩猩的染色质构象图谱，并观察到了 SV 断点处基因组相互作用的改变。最后，我们集中研究了 56 个在>90%的黑猩猩中受到 SV 影响而在人类和大猩猩中缺失的基因，这些基因可能有助于黑猩猩的特异性特征。对来自不同亚种的更多个体进行测序，对于建立黑猩猩遗传变异的完整图谱将是至关重要的。
