SNP Discovery Using a Pangenome: Has the Single Reference Approach Become Obsolete?

Abstract

Increasing evidence suggests that a single individual is insufficient to capture the genetic diversity within a species due to gene presence absence variation. In order to understand the extent to which genomic variation occurs in a species, the construction of its pangenome is necessary. The pangenome represents the complete set of genes of a species; it is composed of core genes, which are present in all individuals, and variable genes, which are present only in some individuals. Aside from variations at the gene level, single nucleotide polymorphisms (SNPs) are also an important form of genetic variation. The advent of next-generation sequencing (NGS) coupled with the heritability of SNPs make them ideal markers for genetic analysis of human, animal, and microbial data. SNPs have also been extensively used in crop genetics for association mapping, quantitative trait loci (QTL) analysis, analysis of genetic diversity, and phylogenetic analysis. This review focuses on the use of pangenomes for SNP discovery. It highlights the advantages of using a pangenome rather than a single reference for this purpose. This review also demonstrates how extra information not captured in a single reference alone can be used to provide additional support for linking genotypic data to phenotypic data.

Characterization of disease resistance genes in the Brassica napus pangenome reveals significant structural variation

“…The term ‘pangenome’ includes the complete and non‐redundant set of genes in the entire species; it is composed of core genes, which are present in all individuals, and variable genes, which are present only in some individuals (Golicz et al ., 2016a; Hurgobin and Edwards, ). Variable genes can be split into two groups: CNVs, in which the number of copies of a gene differs between individuals, and PAVs, an extreme form of CNV in which a gene is present in some individuals but absent in others (Golicz et al ., 2016a; Saxena et al ., ).…”

“…With the advent of reference genome sequences, genomic approaches can be used to discover specific genes and subsequent association of candidate genes with heritable traits (Edwards et al, 2011;Qiu et al, 2013). However, a single reference genome cannot cover the entire gene content of a species due to structural variations, such as gene presence/ absence variations (PAVs) or copy number variations (CNVs) (Gan et al, 2011;Golicz et al, 2016a;Hurgobin and Edwards, 2017). To address this issue, pangenomes have been constructed for a number of plant species, including maize, soya bean, rice, wheat and Brassica species (Golicz et al, 2016b;Hirsch et al, 2014;Hurgobin et al, 2018;Li et al, 2014;Lin et al, 2014;Montenegro et al, 2017;Yao et al, 2015).…”

Genomic diversity affects the accuracy of bacterial SNP calling pipelines

“…However, long-read platforms can also, in principle if not yet routinely, generate complete de novo bacterial genomes [79] for downstream SNP calling, possibly removing the need to choose a reference entirely. Similarly, using a reference pan-genome instead of a singular representative genome could also maximise the number of SNP calls by reducing the number of genes not present in the reference [80].…”

Integrating genomics for chickpea improvement: achievements and opportunities

“…However, single genome-based breeding efforts are able to capture limited diversity, and therefore, there is need to deploy pangenome approaches to capture entire diversity present in a species. Scope and applications of pangenome (core and dispensable) have been nicely described by Hurgobin and Edwards (2017). Pangenomes can also differentiate among variations in core (conserved across all individuals of the species) and dispensable (variable among individuals of a species) genomes.…”