Scientists have released the first complete sequencing of the human Y chromosome

Now men who feel misunderstood by their wives or by all the women in the world can breathe a sigh of relief. for decades, Y chromosome – one of the two human sex chromosomes – has been a major challenge to the genomics community to sequence due to the complexity of its structure.

Now, this elusive region of the genome has been fully sequenced, a feat that finally completes the comprehensive set of human chromosomes and adds 30 million new bases to the genome. human genome Reference – Mostly satellite DNA which is difficult to sequence. These bases reveal an additional 41 protein-coding genes and provide vital insight for those studying important questions of reproduction, evolution, and population change.

The discovery was made by researchers from the Telomere-to-Telomere (T2T) Consortium, which includes dozens of researchers, most from across the United States. The group is co-led by Biomolecular Engineering Assistant Professor Karen Mega of the University of California, Santa Cruz (UCSC). They just announced this achievement in a new paper just published in the prestigious journal nature Entitled “Researchers Collect First Complete Human Y-chromosome Sequence.” The fully annotated Y chromosome reference is accessible on the UCSC Genome Browser and via Github.

“Just a few years ago, half of the human Y chromosome was missing from the reference — difficult, complex satellite regions,” said Dr. “At the time, we didn’t even know if it could be sequenced, it was very confusing. This is really a huge shift in what’s possible.

When scientists and clinicians study the genome of an individual, they compare the individual’s DNA with the DNA of a standard reference to determine where the difference is. To date, the Y chromosome portion of the human genome contains large gaps that make it difficult to understand the diversity and associated diseases.

Geneticist Karen Mega in a lab used for research related to the human Y chromosome, at the University of California, Santa Cruz, California, US, February 10, 2022. (Credit: Caroline Lagatota, University of California, Santa Cruz/Handout via Reuters)

Why is the Y chromosome so difficult to decode?

Deciphering the structure of the Y chromosome has been challenging because some DNA is organized into homologues—long sequences of symmetrical forwards and backwards—spanning more than a million base pairs. In addition, a very large portion of the Y chromosome that was missing from the earlier version of the Y reference is satellite DNA – large, highly repetitive regions of non-protein-coding DNA. On the Y chromosome, there are two satellites that are linked together, which increases the complexity of the sequencing process.

The researchers were able to read Y chromosome sequences without gaps thanks to advances in long-read sequencing technology and innovative new computational clustering methods that can handle repeated sequences and convert raw data from the sequence into a usable resource. These new combinations of methods allowed the team to tackle some particularly difficult aspects of the Y chromosome, such as pinpointing exactly where in the alternating chromosome the inversion occurred. The methods presented in the paper will allow scientists to complete more comprehensive reads of human Y chromosomes to gain a better understanding of how this genetic material affects diverse human populations.

“It was the Y chromosome that lacked most of the sequences from the previous reference genome,” said Dr. Arang Rhee, a computer scientist at the US National Human Genome Research Institute and lead author of the study. “It was always upsetting to know that we were missing half of a Y whenever we tried to do any reference-based analysis. I was really excited to curate the first full Y, to see what we were really missing, and what we can do now.

In 2018, Mega and her colleagues released the first complete map of the human centromere on the Y chromosome. Now, just five years later, the T2T consortium has populated an additional 30 million base pairs, as well as the first fully sequenced human genome which will be released in 2022.

The Y chromosome is most commonly associated with individuals identified as male at birth, but it can be found in others, such as intersex people. the sexual characteristics regulated by DNA on the Y chromosome also does not equate to an individual’s gender identity. While there are relatively few genes on the Y chromosome, the genes that do exist are complex and dynamic, encoding important functions such as spermatogenesis and sperm production. A full reference to the Y chromosome will allow scientists to better study a large number of features about this part of the human genome in a way that was not possible before.

Having a clearer picture of the Y chromosome makes it easier to track genes through generations of inheritance and see how the location and content of genes have changed over time. The 30 million new bases will also be crucial for studying the evolution of the genome.

The complete sequence also reveals important features of medically related areas. One such section of the Y chromosome is called the azoospermia factor region, which is a stretch of DNA that contains several genes known to be involved in sperm production. With the newly completed sequencing, the researchers studied the structure of a set of inverted, or ‘palindromic’, repeats in the azoospermia factor region.

“It is exciting to finally be able to see these sequences in highly populated regions for the first time. Finally, we can design experiments to test the effect and function of these previously unexplored parts of the Y chromosome,” Mega said.

While the complete human Y chromosome will open the door to many new discoveries, the researchers plan to further improve the study of this region by including the Y chromosome in future versions of the Human Genome, a new reference for genomics that collects genomic information for microorganisms. Many people from different ancestral backgrounds to ultimately enable more research and fairer clinical discoveries, such as helping to diagnose disease, predict medical outcomes, and guide treatments.

Leave a Comment

Your email address will not be published. Required fields are marked *

Scroll to Top