Pioneering Genetics Research: The Male Sex Chromosome is finally understood

Researchers, including those from Johns Hopkins University, have successfully sequenced the Y chromosome, which is associated with male development. This breakthrough illuminates the genetic code of the Y chromosome and improves understanding of male-specific development, fertility, and genetic diseases. The breakthrough, made possible by modern sequencing technology, reveals the nature of important genes and provides the impetus for the advancement of human medicine.

A global team of scientists has completely sequenced the Y chromosome, expanding our understanding of male development, fertility, and genetic diseases.

The chromosome associated with male development, the last mysterious part of the human genome, has been completely sequenced by a team of more than 100 researchers from around the world including scientists from Johns Hopkins University.

The breakthrough completes the genetic code of the Y chromosome and reveals key details that could provide a clearer picture of the chromosome’s role in male-specific development, reproduction, and genetic diseases such as cancer.

The work was recently published in a journal Nature.

“Now that we have this 100% complete sequence of the Y chromosome, we can identify and analyze many genetic variations that may affect human behavior and disease in a way we could not do before,” said the co-author. Dylan Taylor, Johns Hopkins geneticist and doctoral candidate.

Sequence of DNA consisting of chromosomes contain genes and genetic circuits that guide the development and function of all cells in living things. The Y chromosome has been very difficult to decipher due to repeating molecular patterns, but new sequencing technology and bioinformatics algorithms allowed the team to decipher this DNA sequence.

Unraveling the Hidden Genetic Structure

The team identified parts of the gene families that control sperm and discovered 41 additional genes on the Y chromosome. They also identified genetic structures thought to play an important role in the development and function of the male reproductive system.

“We’ve completed the wiring diagram of all these genetic switches that work on the Y chromosome, many of which are very important in the genetic contribution to male development,” said lead author Michael Schatz, a Bloomberg Distinguished Professor of computer science, biology and oncology. at Johns Hopkins. “We are at a stage where scientists can start using this map. “We used to be blind to different parts of the genome and different mutations, but now that we can see the whole genome, we hope to add new information to the genes of many different diseases.”

The Y chromosome, along with the X chromosome, is often discussed for its role in sexual development. While these chromosomes play a central role, the factors involved in the development of human sexuality are spread throughout the genome and are very complex, giving rise to the range of human sexual characteristics found in males, females and heterosexuals. These categories are not equal to gender, which is a social category. In addition, recent work shows that genes on the Y chromosome contribute to other aspects of human biology, such as cancer risk and obesity.

Contributions to the Genome Landscape

The research was led by the National Human Genome Research Institute, part of the Telomere-to-Telomere consortium that in 2022 revealed the complete sequence of the human genome decades ago – making a revelation that is expected to open new lines of molecules and genes. to explore. However, that work is done with two X chromosomes. Now, using a donor with both X and Y chromosomes, the organization has created a complete blueprint of the Y chromosome and all of its DNA.

The new discoveries lay the foundation for high-quality genome assemblies that did not exist before, including personalized genomes.

“The genome is a very personal thing, it contains the basic instructions for the building blocks of our development and what makes us human,” said co-author Rajiv McCoy, a Johns Hopkins assistant professor of biology. “We knew we had an incomplete picture until now, but now we can see the entire genome from end to end.”

The Johns Hopkins team compared the new Y chromosome sequence against genetic data from thousands of people around the world. Their analysis identified errors in the previous reference genome, and showed how the new Y chromosome sequence will improve future studies of human DNA.

They combine new insights from studies of primates both to dig deeper into the evolution of the Y chromosome and to analyze clinically relevant genes that may impact human medicine for pancreatic cancer and other diseases.

Related research:

Reference: “Assembly of 43 human Y chromosomes reveals extensive complexity and diversity” by Pille Hallast, Peter Ebert, Mark Loftus, Feyza Yilmaz, Peter A. Audano, Glennis A. Logsdon, Marc Jan Bonder, Weichen Zhou, Wolfram Höps, Kwondo Kim , Chong Li, Savannah J. Hoyt, Philip C. Dishuck, David Porubsky, Fotios Tsetsos, Jee Young Kwon, Qihui Zhu, Katherine M. Munson, Patrick Hasenfeld, William T. Harvey, Alexandra P. Lewis, Jennifer Kordosky, Kendra Hoekzema, Human Genome Structural Variation Consortium (HGSVC), Rachel J. O’Neill, Jan O. Korbel, Chris Tyler-Smith, Evan E. Eichler, Xinghua Shi, Christine R. Beck, Tobias Marschall, Miriam K. Konkel and Charles Lee Lee , 23 August 2023, Nature.
DOI: 10.1038/s41586-023-06425-6

Funding: NIH/National Institutes of Healththe National Science Foundation