Genomic architecture and functional effects of potential human inversion supergenes
Campoy, Elena (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Puig Font, Marta (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Yakymenko, Illya (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Lerga Jaso, Jon (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Cáceres Aguilar, Mario (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Data:	2022
Resum:	Supergenes are involved in adaptation in multiple organisms, but they are little known in humans. Genomic inversions are the most common mechanism of supergene generation and maintenance. Here, we review the information about two large inversions that are the best examples of potential human supergenes. In addition, we do an integrative analysis of the newest data to understand better their functional effects and underlying genetic changes. We have found that the highly divergent haplotypes of the 17q21. 31 inversion of approximately 1. 5 Mb have multiple phenotypic associations, with consistent effects in brain-related traits, red and white blood cells, lung function, male and female characteristics and disease risk. By combining gene expression and nucleotide variation data, we also analysed the molecular differences between haplotypes, including gene duplications, amino acid substitutions and regulatory changes, and identify CRHR1, KANLS1 and MAPT as good candidates to be responsible for these phenotypes. The situation is more complex for the 8p23. 1 inversion, where there is no clear genetic differentiation. However, the inversion is associated with several related phenotypes and gene expression differences that could be linked to haplotypes specific of one orientation. Our work, therefore, contributes to the characterization of both exceptional variants and illustrates the important role of inversions. This article is part of the theme issue 'Genomic architecture of supergenes: causes and evolutionary consequences'.
Ajuts:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1379 Agencia Estatal de Investigación BFU2016-77244-R Agencia Estatal de Investigación PID2019-107836RB-I00 Agencia Estatal de Investigación BES-2017-082018 Agencia Estatal de Investigación PRE-2020-092440
Drets:	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, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Inversions ; Supergenes ; Humans ; Phenotypic traits ; Gene expression
Publicat a:	Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 377, Issue 1856 (August 2022) , art. 20210209, ISSN 1471-2970

DOI: 10.1098/rstb.2021.0209
PMID: 35694745

11 p, 1.0 MB

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