Fig. 1

The reference genome is a type specimen. a Cumulative distributions of variants in the reference genome and those in personal/individual genomes. If we collapse the diploid whole genomes genotyped in the 1000 Genomes Project into haploid genomes, we can observe just how similar the reference is to an individual genome. First, taking population allele frequencies from a random sample of 100 individual genomes, we generated new haploid ‘reference’ sequences. We replaced the alleles of the reference genome with the personal homozygous variant, and a randomly chosen heterozygous allele. For simplicity, all calculations were performed against the autosomal chromosomes of the GRCh37 assembly and include only single nucleotide bi-allelic variants (i.e., only two alleles per single nucleotide polymorphism (SNP)). b Cumulative distributions of allele frequencies for variants called in 100 randomly chosen personal genomes, computed against the reference genome. Here, the presence of a variant with respect to the reference is quite likely to mean that the reference itself has the ‘variant’ with respect to any default expectation, particularly if the variant is homozygous