Researchers Identify a Completed Sequence of the Y Chromosome

A recent article published in Nature revealed that researchers have finally sequenced the human Y chromosome, marking the final human chromosome to be evaluated. The study, which was funded by the National Human Genome Research Institute (NHGRI), a subset of the National Institutes of Health (NIH), was led by researchers from the Telomere-to-Telomere (T2T) Consortium.

Roughly two decades ago, scientists developed the first human genome sequence; however, that sequence was incomplete. As sequencing tools have advanced, researchers began filling in the gaps. Despite significant additions, a large portion of the Y chromosome remained unmapped.

Researchers needed help analyzing the Y chromosome due to the unusual number of repetitive sequences found in this chromosome. However, using new DNA sequencing technologies, investigators at the T2T Consortium were able to fill some of the gaps.

“The biggest surprise was how organized the repeats are,” said Adam Phillippy, PhD, a senior investigator at NHGRI and consortium leader, in the NIH press release. “We didn’t know what exactly made up the missing sequence. It could have been very chaotic, but instead, nearly half of the chromosome is made of alternating blocks of two specific repeating sequences known as satellite DNA. It makes a beautiful, quilt-like pattern.”

The researchers found that one section of the chromosome, the azoospermia factor region, is responsible for sperm production. Deletions in the palindromes that comprise these regions could significantly impact sperm production and fertility.

“This structure is very important because occasionally these palindromes can create loops of DNA,” said Arang Rhie, PhD, NHGRI staff scientist and first author of the Nature publication. “Sometimes, these loops accidentally get cut off and create deletions in the genome.”

The study also revealed changes in the TSPY gene, which is theorized to be involved in sperm production. Researchers found that copies of the gene varied from 10 to 40 copies depending on the individual.

“When you find variation that you haven't seen before, the hope is always that those genomic variants will be important for understanding human health,” added Phillippy. “Medically relevant genomic variants can help us design better diagnostics in the future.”

Overall, the study identified 62,460,029 base-pair sequences for a complete map of the human Y chromosome. These advancements include more than 30 million base pairs that were not previously identified. With this new information, researchers may gain a better understanding of the role of the Y chromosome beyond determining biological sex.