Detailed analysis of inversions predicted between two human genomes: errors, real polymorphisms, and their origin and population distribution.

Autor:	Vicente-Salvador D; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain., Puig M; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain., Gayà-Vidal M; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain., Pacheco S; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain., Giner-Delgado C; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain.; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, (Barcelona), Spain., Noguera I; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain., Izquierdo D; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain., Martínez-Fundichely A; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain., Ruiz-Herrera A; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain.; Departament de Biologia Celular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain., Estivill X; Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), Barcelona, Spain.; Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain., Aguado C; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain., Lucas-Lledó JI; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain.; Institut Cavanilles de Biodiversitat i Biologia Evolutiva, Universitat de València, Paterna (València), Spain and., Cáceres M; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain.; ICREA, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Human molecular genetics [Hum Mol Genet] 2017 Feb 01; Vol. 26 (3), pp. 567-581.
DOI:	10.1093/hmg/ddw415
Abstrakt:	The growing catalogue of structural variants in humans often overlooks inversions as one of the most difficult types of variation to study, even though they affect phenotypic traits in diverse organisms. Here, we have analysed in detail 90 inversions predicted from the comparison of two independently assembled human genomes: the reference genome (NCBI36/HG18) and HuRef. Surprisingly, we found that two thirds of these predictions (62) represent errors either in assembly comparison or in one of the assemblies, including 27 misassembled regions in HG18. Next, we validated 22 of the remaining 28 potential polymorphic inversions using different PCR techniques and characterized their breakpoints and ancestral state. In addition, we determined experimentally the derived allele frequency in Europeans for 17 inversions (DAF = 0.01-0.80), as well as the distribution in 14 worldwide populations for 12 of them based on the 1000 Genomes Project data. Among the validated inversions, nine have inverted repeats (IRs) at their breakpoints, and two show nucleotide variation patterns consistent with a recurrent origin. Conversely, inversions without IRs have a unique origin and almost all of them show deletions or insertions at the breakpoints in the derived allele mediated by microhomology sequences, which highlights the importance of mechanisms like FoSTeS/MMBIR in the generation of complex rearrangements in the human genome. Finally, we found several inversions located within genes and at least one candidate to be positively selected in Africa. Thus, our study emphasizes the importance of careful analysis and validation of large-scale genomic predictions to extract reliable biological conclusions. (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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