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Home / A New Study Has Managed To Uncover The Centromere of The Y Chromosome.

A New Study Has Managed To Uncover The Centromere of The Y Chromosome.

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13 APR

A New Study Has Managed To Uncover The Centromere of The Y Chromosome

In an effort to solve this genetic cypher, the Human Genome Project, a collaborative international consortium, was created. The goal was to read out the DNA sequence – made up of four letters, or bases, A,T,G and C – of all human genes (genome). In 2003, a near-complete map of the human genome was reported. Yet, the assembled genome represented only 92% of all human genes. Gaps remained that could not be easily decrypted. For many researchers, that elusive 8% of the genome is a holy grail.

The unmappable genome is associated with "heterochromatin" (dark matter of the genome, highly condensed), unlike "euchromatin" (light matter, more loosely wound part of the genome). Euchromatin is gene-rich while heterochromatin refers to the silent, repressed regions of our DNA. Euchromatin is full of unique DNA sequences. This means that finding a single- or low-copy DNA sequence, with all the same DNA bases in the same order, at more than one location in our genome is highly unlikely. These discrete DNA sequences are easily distinguishable and serve distinct purposes within our cells. No wonder the human genome has almost 20,000 different genes with limited redundancy. Now, visualize a human chromosome as a big "X", made of coiled-up DNA, with two arms attached at a constriction. Heterochromatin is mostly localised near the point of attachment (centromere) and the tips of the arms (telomeres). In fact, the centromere becomes indispensable when cells divide, dragging along one chromosome arm into each of the newly formed daughter cells.

The new study, from the team of Dr. Karen Miga at University of California (Santa Cruz), has managed to uncover the centromere of the Y chromosome – the male-specific chromosome and also the smallest chromosome in our genome (something worth thinking about). The researchers were able to insert a longer stretch of DNA into a nanopore (like thread passed through the eye of a needle), "resulting in complete, end-to-end sequence coverage of the entire insert". Using this nanopore-sequencing method, the researchers can now decipher a long, muddled DNA stretch full of repeats. This "long-read" strategy allowed them to string together longer pieces of DNA (made up of variable repeat monomer lengths). It turns out that when all these chunks are laid out, certain clues help reconstruct the repetitive-sequence. Walking along the centromere, from left to right, context is provided by surrounding monomers in the same tandem array and by flanking non-repetitive DNA.

Like a neatly laid section of railroad, the authors pieced together a chain of contiguous DNA sequences and solved the jigsaw puzzle of the Y chromosome centromere. This recent work, published in Nature Biotechnology journal, plugs holes in the existing human DNA map. In the future, finding out the DNA sequences that define other centromeres will allow researchers to rewrite, manipulate, alter or duplicate these key structures. Given that the centromere is essential for cells to divide and segregate their genetic content to future generations, the Y centromere assembly represents an exciting step forward in modern biology.

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