Dataset Information

Inference of population structure using dense haplotype data.

ABSTRACT: The advent of genome-wide dense variation data provides an opportunity to investigate ancestry in unprecedented detail, but presents new statistical challenges. We propose a novel inference framework that aims to efficiently capture information on population structure provided by patterns of haplotype similarity. Each individual in a sample is considered in turn as a recipient, whose chromosomes are reconstructed using chunks of DNA donated by the other individuals. Results of this "chromosome painting" can be summarized as a "coancestry matrix," which directly reveals key information about ancestral relationships among individuals. If markers are viewed as independent, we show that this matrix almost completely captures the information used by both standard Principal Components Analysis (PCA) and model-based approaches such as STRUCTURE in a unified manner. Furthermore, when markers are in linkage disequilibrium, the matrix combines information across successive markers to increase the ability to discern fine-scale population structure using PCA. In parallel, we have developed an efficient model-based approach to identify discrete populations using this matrix, which offers advantages over PCA in terms of interpretability and over existing clustering algorithms in terms of speed, number of separable populations, and sensitivity to subtle population structure. We analyse Human Genome Diversity Panel data for 938 individuals and 641,000 markers, and we identify 226 populations reflecting differences on continental, regional, local, and family scales. We present multiple lines of evidence that, while many methods capture similar information among strongly differentiated groups, more subtle population structure in human populations is consistently present at a much finer level than currently available geographic labels and is only captured by the haplotype-based approach. The software used for this article, ChromoPainter and fineSTRUCTURE, is available from http://www.paintmychromosomes.com/.

SUBMITTER: Lawson DJ

PROVIDER: S-EPMC3266881 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Inference of population structure using dense haplotype data.

Lawson Daniel John DJ Hellenthal Garrett G Myers Simon S Falush Daniel D

PLoS genetics 20120126 1

The advent of genome-wide dense variation data provides an opportunity to investigate ancestry in unprecedented detail, but presents new statistical challenges. We propose a novel inference framework that aims to efficiently capture information on population structure provided by patterns of haplotype similarity. Each individual in a sample is considered in turn as a recipient, whose chromosomes are reconstructed using chunks of DNA donated by the other individuals. Results of this "chromosome p ...[more]

PMID: 22291602

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Project description:Genomic regions of autozygosity (ROA) arise when an individual is homozygous for haplotypes inherited identical-by-descent from ancestors shared by both parents. Over the past decade, they have gained importance for understanding evolutionary history and the genetic basis of complex diseases and traits. However, methods to infer ROA in dense genotype data have not evolved in step with advances in genome technology that now enable us to rapidly create large high-resolution genotype datasets, limiting our ability to investigate their constituent ROA patterns.We report a weighted likelihood approach for inferring ROA in dense genotype data that accounts for autocorrelation among genotyped positions and the possibilities of unobserved mutation and recombination events, and variability in the confidence of individual genotype calls in whole genome sequence (WGS) data.Forward-time genetic simulations under two demographic scenarios that reflect situations where inbreeding and its effect on fitness are of interest suggest this approach is better powered than existing state-of-the-art methods to infer ROA at marker densities consistent with WGS and popular microarray genotyping platforms used in human and non-human studies. Moreover, we present evidence that suggests this approach is able to distinguish ROA arising via consanguinity from ROA arising via endogamy. Using subsets of The 1000 Genomes Project Phase 3 data we show that, relative to WGS, intermediate and long ROA are captured robustly with popular microarray platforms, while detection of short ROA is more variable and improves with marker density. Worldwide ROA patterns inferred from WGS data are found to accord well with those previously reported on the basis of microarray genotype data. Finally, we highlight the potential of this approach to detect genomic regions enriched for autozygosity signals in one group relative to another based upon comparisons of per-individual autozygosity likelihoods instead of inferred ROA frequencies.This weighted likelihood ROA inference approach can assist population- and disease-geneticists working with a wide variety of data types and species to explore ROA patterns and to identify genomic regions with differential ROA signals among groups, thereby advancing our understanding of evolutionary history and the role of recessive variation in phenotypic variation and disease.

Dataset Information

Inference of population structure using dense haplotype data.

Publications

Inference of population structure using dense haplotype data.

Similar Datasets

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