The complete sequence of a human Y chromosome

Area of Science:

• Genomics
• Human Genetics
• Molecular Biology

Background:

• The human Y chromosome's complex structure, including repeats and duplications, has hindered complete sequencing.
• Over half of the Y chromosome is missing from the current GRCh38 reference genome.
• The Y chromosome is the last human chromosome to be fully sequenced.

Purpose of the Study:

• To present the complete sequence of the human Y chromosome.
• To correct errors in the existing GRCh38 reference sequence.
• To provide a comprehensive reference for human chromosomes.

Main Methods:

• Utilized the Telomere-to-Telomere (T2T) consortium's sequencing approach.
• Sequenced the Y chromosome from the HG002 genome (T2T-Y).
• Combined T2T-Y with the CHM13 genome assembly and mapped genomic data.

Main Results:

• Generated a complete 62,460,029-base-pair sequence of the human Y chromosome (T2T-Y).
• Added over 30 million base pairs to the reference sequence, correcting GRCh38-Y errors.
• Detailed ampliconic structures of TSPY, DAZ, and RBMY gene families, identified 41 new protein-coding genes, and described Yq12 heterochromatic region composition.

Conclusions:

• The T2T-Y sequence provides the first complete human Y chromosome reference.
• This complete sequence enables better understanding of Y chromosome genetics and associated diseases.
• Integration with CHM13 offers a complete reference for all 24 human chromosomes.