WEDNESDAY, Aug. 23, 2023 (HealthDay News) — A global research team has achieved the primary complete sequencing of the human Y chromosome, which is closely linked to male development.

That is the last of the human chromosomes to be fully sequenced, an effort which will make clear every part from fertility to disease.

The work was led by the Telomere-to-Telomere (T2T) Consortium, which is a team of researchers funded by the National Human Genome Research Institute (NHGRI) in Bethesda, Md., a part of the U.S. National Institutes of Health.

The brand new sequence fills in gaps across greater than 50% of the Y chromosome’s length.

The research, published Aug. 23 in Nature, uncovered necessary genomic features, including aspects in sperm production.

While each the X and Y chromosomes have a central role in sexual development, the aspects involved are spread across the genome and really complex, in accordance with the study.

Other recent work has shown that genes on the Y chromosome contribute to other elements of human biology, including cancer risk.

Researchers accomplished the primary human genome sequence 20 years ago, but there have been gaps within the sequences of all 24 chromosomes. While some had just small gaps, greater than half of the Y chromosome’s sequence was unknown.

The Y chromosome is unusually repetitive, which made its sequence particularly difficult to finish.

Study authors explained the challenge with an example of reading a book. If the lines in a book are all unique, then putting together long strips of text to create the book is simpler. If the lines are repeated 1000’s or thousands and thousands of times, it’s hard to find out what the order ought to be.

About 30 million letters of the Y chromosome are repetitive sequences.

The T2T Consortium applied latest DNA sequencing technologies and sequence assembly methods, together with knowledge gained from generating the primary gapless sequences for the opposite 23 human chromosomes, to resolve this mystery.

“The largest surprise was how organized the repeats are,” said Adam Phillippy, a senior investigator at NHGRI and leader of the consortium.

“We didn’t know what exactly made up the missing sequence. It might have been very chaotic, but as a substitute, nearly half of the chromosome is fabricated from alternating blocks of two specific repeating sequences referred to as satellite DNA. It makes a lovely, quilt-like pattern,” he said in a NIH news release.

The research revealed information in regards to the azoospermia factor region, which is a stretch of DNA containing several genes known to be involved in sperm production.

Researchers were in a position to study the structure of a set of inverted repeats or “palindromes” on this region.

“This structure may be very necessary because occasionally these palindromes can create loops of DNA,” said study first creator Arang Rhie, an NHGRI staff scientist. “Sometimes, these loops by chance get cut off and create deletions within the genome.”

Deletions on this region are known to disrupt sperm production, and this might influence fertility. With a whole Y chromosome sequence, now researchers can more precisely analyze these deletions and their effects on sperm production.

Other regions with potential medical relevance contain genes that repeat, in accordance with the study. While most genes within the human genome have two copies, one inherited from each parent, some genes have many copies that repeat along a stretch of DNA, sometimes called a “gene array.”

The researchers focused on the TSPY gene, considered involved in sperm production. Copies of TSPY are organized within the second largest gene array within the human genome, in accordance with the study. Researchers found that different individuals contained between 10 and 40 copies of TSPY.

“While you find variation that you just haven’t seen before, the hope is at all times that those genomic variants might be necessary for understanding human health,” said Phillippy. “Medically relevant genomic variants will help us design higher diagnostics in the long run.”

More information

The Urology Care Foundation has more on male infertility.

SOURCE: NIH/National Human Genome Research Institute, news release, Aug. 23, 2023