期刊
GENOME RESEARCH
卷 30, 期 5, 页码 724-735出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.255273.119
关键词
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资金
- Agencia Estatal de Investigacion (AEI, Spain) [BFU2013-42649-P, BFU2016-77244-R]
- European Regional Development Fund (FEDER, EU)
- ERC from the European Research Council under the European Union Seventh Research Framework Programme (FP7) [243212]
- Generalitat de Catalunya (Spain) [2017-SGR-1379]
- La Caixa Doctoral fellowship
- Operational Programme for Competitiveness Factors (COMPETE, EU) [POCI-01-0145-FEDER-006821]
- Foundation for Science and Technology (FCT, Portugal) [UID/BIA/50027/2013]
- European Research Council (ERC) [243212] Funding Source: European Research Council (ERC)
Despite the interest in characterizing genomic variation, the presence of large repeats at the breakpoints hinders the analysis of many structural variants. This is especially problematic for inversions, since there is typically no gain or loss of DNA. Here, we tested novel linkage-based droplet digital PCR (ddPCR) assays to study 20 inversions ranging from 3.1 to 742 kb flanked by inverted repeats (IRs) up to 134 kb long. Of those, we validated 13 inversions predicted by different genome-wide techniques. In addition, we obtained new experimental human population information across 95 African, European, and East Asian individuals for 16 inversions, including four already validated variants without high-throughput genotyping methods. Through comparison with previous data, independent replicates and both inversion breakpoints, we demonstrate that the technique is highly accurate and reproducible. Most studied inversions are widespread across continents, and their frequency is negatively correlated with genetic length. Moreover, all except two show clear signs of being recurrent, and we could better define the factors affecting recurrence levels and estimate the inversion rate across the genome. Finally, the generated genotypes have allowed us to check inversion functional effects, validating gene expression differences reported before for two inversions and finding new candidate associations. Therefore, the developed methodology makes it possible to screen these and other complex genomic variants quickly in a large number of samples for the first time, highlighting the importance of direct genotyping to assess their potential consequences and clinical implications.
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