Comprehensive Sequencing of the Human Y Chromosome: Implications for Male Fertility and Genomic Variability

Scientists have succeeded in analyzing the entire sequence of the Y chromosome, a task that had not been achieved before. This provides valuable information about its role in sperm production.

Human Chromosomes

The 23 pairs that every human carries have been extensively studied by scientists. But little was known about the Y chromosome, which only men carry. Science had failed to analyze more than half of its sequence. But now, a team of about a hundred scientists has managed to decode it in its entirety. In the journal Nature, these researchers reveal the importance of this chromosome, particularly in terms of reproduction.

The Y chromosome: Why is it so hard to decipher?

All chromosomes contain repetitive sectors, but the Y chromosome is unusually repetitive, making its sequence particularly difficult to complete,” the authors explain in their study. Collecting sequencing data is like trying to read a long book cut into strips. If all the lines in the book are unique, it’s easier to determine the order in which they occur. However, if the same sentence is repeated thousands or millions of times, the original order of the strips is much less clear.”

This group of scientists used new DNA sequencing techniques and computer tools to decipher these millions of repeats. We didn’t know exactly what made up the missing sequence,” warns Adam Phillippy, head of the consortium. It could have been very chaotic, but instead, almost half of the chromosome is made up of alternating blocks of two specific repetitive sequences called satellite DNA.”

What is the role of the Y chromosome?

This complete sequencing also allows us to understand the characteristics of each sector of this chromosome. One of these is called the azoospermia factor region, which contains several genes involved in sperm production. Thanks to recent discoveries, researchers have been able to study inverted repeats, also known as palindromes, in this region. This structure is very important because these palindromes can sometimes create DNA loops,” explains co-author Arang Rhie. Sometimes these loops are accidentally cut and create deletions in the genome.” Deletions in the azoospermia factor region disrupt sperm production, so these palindromes could influence fertility. The consortium’s work will provide a better understanding of their impact on sperm production. But they have also managed to decode a gene called TSPY, which is also linked to sperm production: they found that individuals have between 10 and 40 copies of this gene, which could again improve our understanding of male fertility.

“When you discover variations you’ve never seen before, the hope is always that these genomic variants will become important to our understanding of human health,” says Dr Adam Phillippy. He believes this work could lead to the development of new and more effective diagnostic tools. Ultimately, the findings will potentially contribute to better management of infertility. According to the World Health Organisation, infertility affects 186 million people worldwide.