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Selective single molecule sequencing and assembly of a human Y chromosome of African origin


Mammalian Y chromosomes are often neglected from genomic analysis. Due to their inherent assembly difficulties, high repeat content, and large ampliconic regions, only a handful of species have their Y chromosome properly characterized. To date, just a single human reference quality Y chromosome, of European ancestry, is available due to a lack of accessible methodology. To facilitate the assembly of such complicated genomic territory, we developed a novel strategy to sequence native, unamplified flow sorted DNA on a MinION nanopore sequencing device. Our approach yields a highly continuous assembly of the first human Y chromosome of African origin. It constitutes a significant improvement over comparable previous methods, increasing continuity by more than 800%. Sequencing native DNA also allows to take advantage of the nanopore signal data to detect epigenetic modifications in situ. This approach is in theory generalizable to any species simplifying the assembly of extremely large and repetitive genomes.

Authors: Lukas F.K. Kuderna, Esther Lizano, Eva Julia, Jessica Gomez-Garrido, Aitor Serres-Armero, Martin Kuhlwilm, Regina Antoni Alandes, Marina Alvarez-Estape, Tyler Alioto, Marta Gut, Ivo Gut, Mikkel Heide Schierup, Oscar Fornas, Tomas Marques-Bonet

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