Large-scale analysis of tandem repeat variability in the human genome

Tandem repeats are short DNA sequences that are repeated head-to-tail with a propensity to be variable. They constitute a significant proportion of the human genome, also occurring within coding and regulatory regions. Variation in these repeats can alter the function and/or expression of genes allo...

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Autores principales: Duitama, Jorge, Zablotskaya, Alena, Gemayel, Rita, Jansen, An, Belet, Stefanie, Vermeesch, Joris R, Verstrepen, Kevin J., Froyen, Guy
Formato: Journal Article
Lenguaje:Inglés
Publicado: Oxford University Press 2014
Materias:
Acceso en línea:https://hdl.handle.net/10568/41887
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author Duitama, Jorge
Zablotskaya, Alena
Gemayel, Rita
Jansen, An
Belet, Stefanie
Vermeesch, Joris R
Verstrepen, Kevin J.
Froyen, Guy
author_browse Belet, Stefanie
Duitama, Jorge
Froyen, Guy
Gemayel, Rita
Jansen, An
Vermeesch, Joris R
Verstrepen, Kevin J.
Zablotskaya, Alena
author_facet Duitama, Jorge
Zablotskaya, Alena
Gemayel, Rita
Jansen, An
Belet, Stefanie
Vermeesch, Joris R
Verstrepen, Kevin J.
Froyen, Guy
author_sort Duitama, Jorge
collection Repository of Agricultural Research Outputs (CGSpace)
description Tandem repeats are short DNA sequences that are repeated head-to-tail with a propensity to be variable. They constitute a significant proportion of the human genome, also occurring within coding and regulatory regions. Variation in these repeats can alter the function and/or expression of genes allowing organisms to swiftly adapt to novel environments. Importantly, some repeat expansions have also been linked to certain neurodegenerative diseases. Therefore, accurate sequencing of tandem repeats could contribute to our understanding of common phenotypic variability and might uncover missing genetic factors in idiopathic clinical conditions. However, despite long-standing evidence for the functional role of repeats, they are largely ignored because of technical limitations in sequencing, mapping and typing. Here, we report on a novel capture technique and data filtering protocol that allowed simultaneous sequencing of thousands of tandem repeats in the human genomes of a three generation family using GS-FLX-plus Titanium technology. Our results demonstrated that up to 7.6% of tandem repeats in this family (4% in coding sequences) differ from the reference sequence, and identified a de novo variation in the family tree. The method opens new routes to look at this underappreciated type of genetic variability, including the identification of novel disease-related repeats.
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spelling CGSpace418872025-03-13T09:45:27Z Large-scale analysis of tandem repeat variability in the human genome Duitama, Jorge Zablotskaya, Alena Gemayel, Rita Jansen, An Belet, Stefanie Vermeesch, Joris R Verstrepen, Kevin J. Froyen, Guy secuencia de adn dna sequence Tandem repeats are short DNA sequences that are repeated head-to-tail with a propensity to be variable. They constitute a significant proportion of the human genome, also occurring within coding and regulatory regions. Variation in these repeats can alter the function and/or expression of genes allowing organisms to swiftly adapt to novel environments. Importantly, some repeat expansions have also been linked to certain neurodegenerative diseases. Therefore, accurate sequencing of tandem repeats could contribute to our understanding of common phenotypic variability and might uncover missing genetic factors in idiopathic clinical conditions. However, despite long-standing evidence for the functional role of repeats, they are largely ignored because of technical limitations in sequencing, mapping and typing. Here, we report on a novel capture technique and data filtering protocol that allowed simultaneous sequencing of thousands of tandem repeats in the human genomes of a three generation family using GS-FLX-plus Titanium technology. Our results demonstrated that up to 7.6% of tandem repeats in this family (4% in coding sequences) differ from the reference sequence, and identified a de novo variation in the family tree. The method opens new routes to look at this underappreciated type of genetic variability, including the identification of novel disease-related repeats. 2014-05-14 2014-08-01T13:47:38Z 2014-08-01T13:47:38Z Journal Article https://hdl.handle.net/10568/41887 en Open Access Oxford University Press Duitama J, Zablotskaya A, Gemayel R, Jansen A, Belet S, Vermeesch JR, Verstrepen KJ, Froyen G. 2014. Large-scale analysis of tandem repeat variability in the human genome. Nucleic Acids Research 42(9):5728-5741.
spellingShingle secuencia de adn
dna sequence
Duitama, Jorge
Zablotskaya, Alena
Gemayel, Rita
Jansen, An
Belet, Stefanie
Vermeesch, Joris R
Verstrepen, Kevin J.
Froyen, Guy
Large-scale analysis of tandem repeat variability in the human genome
title Large-scale analysis of tandem repeat variability in the human genome
title_full Large-scale analysis of tandem repeat variability in the human genome
title_fullStr Large-scale analysis of tandem repeat variability in the human genome
title_full_unstemmed Large-scale analysis of tandem repeat variability in the human genome
title_short Large-scale analysis of tandem repeat variability in the human genome
title_sort large scale analysis of tandem repeat variability in the human genome
topic secuencia de adn
dna sequence
url https://hdl.handle.net/10568/41887
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