Whole population, genome-wide mapping of hidden relatedness - PubMed (original) (raw)

Comparative Study

Whole population, genome-wide mapping of hidden relatedness

Alexander Gusev et al. Genome Res. 2009 Feb.

Abstract

We present GERMLINE, a robust algorithm for identifying segmental sharing indicative of recent common ancestry between pairs of individuals. Unlike methods with comparable objectives, GERMLINE scales linearly with the number of samples, enabling analysis of whole-genome data in large cohorts. Our approach is based on a dictionary of haplotypes that is used to efficiently discover short exact matches between individuals. We then expand these matches using dynamic programming to identify long, nearly identical segmental sharing that is indicative of relatedness. We use GERMLINE to comprehensively survey hidden relatedness both in the HapMap as well as in a densely typed island population of 3000 individuals. We verify that GERMLINE is in concordance with other methods when they can process the data, and also facilitates analysis of larger scale studies. We bolster these results by demonstrating novel applications of precise analysis of hidden relatedness for (1) identification and resolution of phasing errors and (2) exposing polymorphic deletions that are otherwise challenging to detect. This finding is supported by concordance of detected deletions with other evidence from independent databases and statistical analyses of fluorescence intensity not used by GERMLINE.

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Figures

Figure 1.

Figure 1.

Expected and detected genome-wide sharing (Kosrae Cohort). (Blue, ▲) Expected genome-wide sharing; (green, ■) detected genome-wide sharing.

Figure 2.

Figure 2.

PLINK metrics and share length for equally related pairs. Comparison of PLINK formula image and _Z_1 values with GERMLINE share length for individuals of equal relationship coefficients. (Left) PLINK formula image values; (middle) PLINK _Z_1 values; (right) GERMLINE share length (cM). Error bars, 99% CI.

Figure 3.

Figure 3.

Candidate deletion fluorescence intensity. (Black line) Population average; (open circles) individuals identified as having the deletion; (blue bar at bottom) deletion identified by GERMLINE.

Figure 4.

Figure 4.

Verified candidate deletion regions (top 200). (dbGV) Identified in Database of Genomic Variants; (CNAT) verified by Affymetrix Copy Number Analysis Tool; (Intensity) verified as deviation from population average intensity.

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