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Determining the impact of uncharacterized inversions in the human genome by droplet digital PCR
Puig Font, Marta (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Lerga Jaso, Jon (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Giner Delgado, Carla (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Pacheco, Sarai (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Izquierdo, David (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Delprat Obeaga, Alejandra (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Gayà Vidal, Magdalena (University of Porto. CIBIO/InBIO Research Center in Biodiversity and Genetic Resources (Portugal))
Regan, Jack F. (Digital Biology Center. Bio-Rad Laboratories (USA))
Karlin Neumann, George (Digital Biology Center. Bio-Rad Laboratories (USA))
Cáceres Aguilar, Mario (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Date: 2020
Abstract: 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.
Note: Número d'acord de subvenció MICINN/BFU2013-42649-P
Note: Número d'acord de subvenció MICINN/BFU2016-77244-R
Note: Número d'acord de subvenció EC/FP7/243212
Note: Número d'acord de subvenció AGAUR/2017/SGR-1379
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: article ; recerca ; publishedVersion
Published in: Genome research, Vol. 30, Issue 5 (May 2020) , p. 724-735, ISSN 1549-5469

DOI: 10.1101/gr.255273.119
PMID: 32424072

13 p, 2.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles

 Record created 2020-12-04, last modified 2021-01-17

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