Friday, August 25, 2023

The Y chromosome’s genetic puzzle is finally complete

Amazing stuff! What took so long! E.g. the Human Genome Project was completed in 2003!

"... Researchers sequenced the chromosome, which contains many genes involved in sperm production and fertility, from a male of European descent. The new telomere-to-telomere, or tip-to-tip, construction adds more than 30 million DNA bases to a previously assembled reference Y chromosome, the team reports online August 23 in Nature. It is the final piece of the human pangenome, an effort to catalog all human DNA ...
A separate study, also published online August 23 in Nature, sequenced the entire Y chromosome from 43 people, including 21 of African descent. That study found that the male sex chromosome can vary in length from person to person by millions of DNA bases, meaning that in some people, the chromosome has extra copies of some genes or other bits of DNA. For instance, males may have between 23 to 39 copies of TSPY genes, involved in sperm production, the researchers found. ..."

From the abstract:
"The human Y chromosome has been notoriously difficult to sequence and assemble because of its complex repeat structure that includes long palindromes, tandem repeats and segmental duplications. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, showing the complete ampliconic structures of gene families TSPY, DAZ and RBMY; 41 additional protein-coding genes, mostly from the TSPY family; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region. We have combined T2T-Y with a previous assembly of the CHM13 genome and mapped available population variation, clinical variants and functional genomics data to produce a complete and comprehensive reference sequence for all 24 human chromosomes."

From the abstract of the second paper:
"The prevalence of highly repetitive sequences within the human Y chromosome has prevented its complete assembly to date and led to its systematic omission from genomic analyses. Here we present de novo assemblies of 43 Y chromosomes spanning 182,900 years of human evolution and report considerable diversity in size and structure. Half of the male-specific euchromatic region is subject to large inversions with a greater than twofold higher recurrence rate compared with all other chromosomes. Ampliconic sequences associated with these inversions show differing mutation rates that are sequence context dependent, and some ampliconic genes exhibit evidence for concerted evolution with the acquisition and purging of lineage-specific pseudogenes. The largest heterochromatic region in the human genome, Yq12, is composed of alternating repeat arrays that show extensive variation in the number, size and distribution, but retain a 1:1 copy-number ratio. Finally, our data suggest that the boundary between the recombining pseudoautosomal region 1 and the non-recombining portions of the X and Y chromosomes lies 500 kb away from the currently established boundary. The availability of fully sequence-resolved Y chromosomes from multiple individuals provides a unique opportunity for identifying new associations of traits with specific Y-chromosomal variants and garnering insights into the evolution and function of complex regions of the human genome."

The Y chromosome’s genetic puzzle is finally complete The male sex chromosome can vary in length from person to person by millions of DNA bases

The complete sequence of a human Y chromosome (no public access, but article above has a link to the PDF)

Assembly of 43 human Y chromosomes reveals extensive complexity and variation
(no public access, but article above has a link to the PDF)

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