RT Journal
A1 Gusev, Alexander
A1 Lowe, Jennifer K.
A1 Stoffel, Markus
A1 Daly, Mark J.
A1 Altshuler, David
A1 Breslow, Jan L.
A1 Friedman, Jeffrey M.
A1 Pe'er, Itsik
T1 Whole population, genome-wide mapping of hidden relatedness
JF Genome Research 
JO Genome Research 
YR 2009 
FD February 01 
VO 19 
IS 2 
SP 318 
OP 326 
DO 10.1101/gr.081398.108 
UL http://genome.cshlp.org/content/19/2/318.abstract 
AB 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.