Discovery of rare, diagnostic Yb8/9 elements in diverse human populations.

Background: Polymorphic human elements are excellent tools for assessing population structure, and new retrotransposition events can contribute to disease. Next-generation sequencing has greatly increased the potential to discover elements in human populations, and various sequencing and bioinformatics methods have been designed to tackle the problem of detecting these highly repetitive elements. However, current techniques for discovery may miss rare, polymorphic elements. Combining multiple discovery approaches may provide a better profile of the polymorphic mobilome. Yb8/9 elements have been a focus of our recent studies as they are young subfamilies (~2.3 million years old) that contribute ~30% of recent polymorphic retrotransposition events. Here, we update our ME-Scan methods for detecting elements and apply these methods to discover new insertions in a large set of individuals with diverse ancestral backgrounds.

Results: We identified 5,288 putative insertion events, including several hundred novel Yb8/9 elements from 213 individuals from 18 diverse human populations. Hundreds of these loci were specific to continental populations, and 23 non-reference population-specific loci were validated by PCR. We provide high-quality sequence information for 68 rare Yb8/9 elements, of which 11 have hallmarks of an active source element. Our subfamily distribution of rare Yb8/9 elements is consistent with previous datasets, and may be representative of rare loci. We also find that while ME-Scan and low-coverage, whole-genome sequencing (WGS) detect different elements in 41 1000 Genomes individuals, the two methods yield similar population structure results.

Conclusion: Current methods for discovery may miss rare, polymorphic elements. Therefore, using multiple techniques can provide a more accurate profile of elements in individuals and populations. We improved our false-negative rate as an indicator of sample quality for future ME-Scan experiments. In conclusion, we demonstrate that ME-Scan is a good supplement for next-generation sequencing methods and is well-suited for population-level analyses.