For decades, the Y chromosome, one of the two sex chromosomes in humans, has posed a major challenge to the genomics community in sequencing because of the complexity of its structure. Now that this elusive part of the genome has been fully sequenced, the end-to-end set of human chromosomes has finally been completed and 30 million new bases have been added to the human reference genome, most from hard-to-sequence satellite DNA. These databases reveal 41 additional protein-coding genes and provide important information to those investigating important questions about reproduction, evolution and population change.

Researchers from the Telomer-Telomer (T2T) Consortium, led by Karen Miga, assistant professor of biomolecular engineering at UC Santa Cruz, announced the achievement in a paper published today in the journal Nature. The Fully Annotated Y Chromosome Reference is available in the UCSC Genome Browser and available via Github.

“Just a few years ago half of the human Y chromosome was missing [в еталоні] “They’re complex, complex satellite regions,” said Monika Chekhova, a co-author of the paper and a doctoral student in biomolecular engineering at UCSC. “We didn’t even know if it could be lined up at the time, it was so mysterious. It’s really a big shift in what’s possible.”

The Y chromosome is most often associated with individuals designated as male at birth, but can also be found in other individuals, such as intersex people. Sex characteristics regulated by DNA on the Y chromosome are also not equivalent to one’s gender identity.

When scientists and clinicians examine a person’s genome, they compare their DNA with standard reference DNA to determine where the variations are. Until now, part of the Y chromosome of the human genome contained large gaps, making the variations and associated diseases difficult to understand.

The structure of the Y chromosome was difficult to decipher because some of the DNA was organized into palindromes (the same long sequences back and forth) spanning over a million base pairs. Also, a very large portion of the Y chromosome not found in the previous version of the Y Handbook is satellite DNA; large, highly repetitive regions DNAdoes not encode a protein. On the Y chromosome, the two satellites are linked, further complicating the sequencing process.

The researchers were able to achieve continuous reading of the Y chromosome thanks to advances in long-read sequencing technology and innovative new computational coupling methods that can work with repetitive sequences and turn raw sequencing data into a useful resource.

These new method setups allowed the team to tackle some particularly challenging aspects. Y chromosomes, such as determining the position of an inversion in a palindromic sequence – a method that can be used to find other inversions. Methods developed in the paper will allow scientists to do more reading Y chromosome human to better understand how this genetic material affects the diverse human population. Source