Although the completion of the Human Genome Project was announced 15 years ago, some areas including the centromeres which sit at the middles of chromosome remained unsequenced. Centromeres are DNA sites important for ensuring that chromosomes line up properly during cell division and that each new cell receives the correct set of chromosomes.
These 'black holes of the genome' may be 'critical for understanding the role of genome biology in health and in diseases such as cancer', said Hugh Olsen, at Univerisity of California Santa Cruz, who co-led the study.
The researchers used a new sequencing technology to sequence the human Y chromosome's centromere. The hope this will pave the way for the human genome sequence to eventually be completed.
Sequencing a human genome is like trying to assemble a 360 million-piece jigsaw with no picture to refer to. A DNA sequencer will only read short stretches of DNA at a time, leaving it up to scientists to piece these 'reads' together to assemble a complete genome. Piecing together reads from highly repetitive sections of the genome (eg a stretch where ACAGAC is repeated hundreds of times) is particularly tricky to get right without accidentally adding or missing out repeats from the sequence.
These difficulties are the reason that there are still gaps in our knowledge of the human genome sequence. These gaps are long stretches of repeats, not thought to have a function; and included in them are the centromeres. Chromosomal diseases such as Down's Syndrome as well as some cancers have been linked to centromeres not functioning correctly, so understanding them is vital for future research.
The team has published the sequence of the Y chromosome's centromere in Nature Biotechnology, and this marks the first time that a human centromere has been sequenced.
The researchers used nanopore sequencing technology to get longer reads of the centromere sequence. Having longer reads made it easier to put together an accurate sequence for the centromere and has raised hopes that the same could be done for similar areas of the genome.
Dr Karen Miga at UC Santa Cruz, who led the research, said: 'Prior to our work, no sequence technology, or collection of sequence technologies have been sufficient to ensure proper assembly through these regions.'
She added: 'We are on a trajectory for a complete genome. I, for one, look forward to a day that where we are finally able to roll up our sleeves and study the function of these mysterious sequences.'