The effect of RAD allele dropout on the estimation of genetic variation within and between populations

Inexpensive short-read sequencing technologies applied to reduced representation genomes is revolutionizing genetic research, especially population genetics analysis, by allowing the genotyping of massive numbers of single-nucleotide polymorphisms (SNP) for large numbers of individuals and populations. Restriction site–associated DNA (RAD) sequencing is a recent technique based on the characterization of genomic regions flanking restriction sites. One of its potential drawbacks is the presence of polymor-phism within the restriction site, which makes it impossible to observe the associated SNP allele (i.e. allele dropout, ADO). To investigate the effect of ADO on genetic varia-tion estimated from RADmarkers, we first mathematically derived measures of the effect of ADO on allele frequencies as a function of different parameters within a single popu-lation. We then used RAD data sets simulated using a coalescence model to investigate the magnitude of biases induced by ADO on the estimation of expected heterozygosity and FST under a simple demographic model of divergence between two populations. We found that ADO tends to overestimate genetic variation both within and between popu