BACKGROUND

The disclosed embodiments relate to assessing populations in which a variant of interest may have arisen and propagated and discovering historical populations from the pattern of genetic relationships between people.

Although humans are, genetically speaking, almost entirely identical, small differences in human DNA are responsible for some observed variation between individuals. In fact, by comparing these small differences in DNA of individuals, it is possible to detect long chromosome segments suggestive of inheritance from a recent common ancestor, and then use these detected segments to estimate how closely two people are related. The process of identifying segments suggestive of recent common inheritance is known in population genetics literature as an analysis of identity-by-descent (IBD). IBD analysis can be used to predict the familial relationship between any two people (e.g., second cousins) in a population. Learning about population structure from genetic polymorphism data is an important topic in genetics. The most widely used methods in this area are based on modeling variation in allele frequencies. These methods have shed light, for example, on historical patterns of migration in human populations. To take one example of this, prior genetic studies of the United States (US) have helped to elucidate the diversity of recent immigrants in relation to other parts of the world (e.g. Europe, Africa).

SUMMARY

Disclosed herein are techniques for characterizing variants of interest. Characterizations can provide insights into the origins, migration patterns, and historical and contemporary geographic locations of populations carrying any variant of interest. Since many variants are associated with a phenotype (e.g., a trait, a disease, or another observable characteristic), learning about a variant's origin and distribution can provide insight into the etiology of the associated phenotype and can be extended to targeting at-risk populations.

In one embodiment, a method for characterizing a variant of interest includes obtaining a DNA dataset from an individual. Genotypes of the individual are determined based on the DNA dataset. A set of reference DNA datasets is accessed. Each reference DNA dataset is associated with a reference individual, and each reference individual is a carrier of a variant at a genetic locus. In some embodiments, a phenotype or haplotype may also be chosen. A cluster includes reference individuals and additional individuals who share Identity-by-Descent (IBD) with the reference individuals is generated. The cluster may be generated based on an IBD affinity between the reference individuals and the additional individuals. In some embodiments, the cluster includes nodes, which represent individuals, and weighted edges, which represent the IBD affinity between individuals. To characterize the variant, the identified cluster is annotated with genealogical data (e.g., birth locations, surnames, ancestral birth locations, residences) based on information about the individuals in the cluster. Statistics of the genealogical data are generated to characterize the variant. Results summarizing the characterization of the variant are generated. If it is determined that the individual shares IBD with the cluster at the genetic locus, a report summarizing the characterization of the variant is provided for display.

In various embodiments, the techniques disclosed herein may additionally be used for predicting assignments of individuals to communities based on obtained genetic information. A DNA dataset is obtained for an individual. Genotypes of the individual are determined based on the DNA dataset. The genotypes are phased to generate haplotypes of the individual, and a subset of haplotypes of the individual are selected. A subset is chosen based on the features of a community of interest. The subset of the haplotypes is inputted into a community-specific model to determine whether the individual is a member of the community. The model is trained using training samples, where each training sample includes a group of haplotypes of a reference individual and a label identifying whether the reference individual belongs to the community. The reference individuals who belong to the community have one or more groups of haplotypes that are representative of the community. Haplotypes that are representative of the community may be identified by performing an enrichment analysis on haplotypes that are common among individual who are known members of the community. Based on the output of the model, it is determined whether the individual is a member of the community.

