TOOLS AND RESOURCES A variant-centric perspective on geographic patterns of human allele frequency variation Arjun Biddanda, Daniel P Rice, John Novembre* Department of Human Genetics, University of Chicago, Chicago, United States Abstract A key challenge in human genetics is to understand the geographic distribution of human genetic variation. Often genetic variation is described by showing relationships among populations or individuals, drawing inferences over many variants. Here, we introduce an alternative representation of genetic variation that reveals the relative abundance of different allele frequency patterns. This approach allows viewers to easily see several features of human genetic structure: (1) most variants are rare and geographically localized, (2) variants that are common in a single geographic region are more likely to be shared across the globe than to be private to that region, and (3) where two individuals differ, it is most often due to variants that are found globally, regardless of whether the individuals are from the same region or different regions. Our variant- centric visualization clarifies the geographic patterns of human variation and can help address misconceptions about genetic differentiation among populations. Introduction Understanding human genetic variation, including its origins and its consequences, is one of the long-standing challenges of human biology. A first step is to learn the fundamental aspects of how human genomes vary within and between populations. For example, how often do variants have an *For correspondence: allele at high frequency in one narrow region of the world that is absent everywhere else? For
[email protected] answering many applied questions, we need to know how many variants show any particular geo- graphic pattern in their allele frequencies.