Y chromosome sequence and epigenomic reconstruction across human populations

Abstract

24 Recent advances in long-read sequencing technologies have allowed the generation and 25 curation of more complete genome assemblies, enabling the analysis of traditionally 26 neglected chromosomes, such as the human Y chromosome (chrY). Native DNA was 27 sequenced on a MinION Oxford Nanopore Technologies sequencing device to generate 28 genome assemblies for 7 major chrY human haplogroups. We analyzed and compared 29 the chrY enrichment of sequencing data obtained using two different selective 30 sequencing approaches: adaptive sampling and flow cytometry chromosome sorting. We 31 show that adaptive sampling can produce data to create assemblies comparable to 32 chromosome sorting while being a less expensive and time-consuming technique. We 33 also assessed haplogroup-specific structural variants, which would be otherwise difficult 34 to study using short-read sequencing data only. Finally, we took advantage of this 35 technology to detect and profile epigenetic modifications amongst the considered 36 haplogroups. Altogether, we provide a framework to study complex genomic regions with 37 a simple, fast, and affordable methodology that could be applied to larger population 38 genomics datasets. 39 bioRxiv preprint doi: https://doi.org/10.1101/2022.12.02.518894; this version posted December 4, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. 40