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The X chromosome is not, in fact, X-shaped

A paper published in Nature this week describes the first 3D model of the X chromosome - and it's not X-shaped.

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But, once the cells have split, things get more complicated. Now, the chromosomes are unwound and un-cinched from their convenient bundles, glopping together so that it’s difficult to tell one chromosome from another. That has presented a problem not just for science textbooks, but also for scientists, who, while knowing that chromosomes look in general like pooled spaghetti, have not had an exact map for the twists and turns of an individual chromosome.

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That's a problem since this complicated post-split state is the normal state of a cell, while the neat, mitosis state is just a brief one: at any given time, about 99.9 percent of the cells in a human are not dividing, says Dr. Fraser.

“We had no understanding of the chromosomes in a cell in its natural state,” he said.

In the researcher, Fraser and colleagues at the Brabraham Institute, as well as at the University of Cambridge and the Weizmann Institute, used measurements of multiple X chromosomes from mice’s cells. The resulting model looks like a heap of threaded-up vermicelli. If there’s an X shape to be found, its buried in the lump.

The researchers also found that the X chromosomes in different cells varied from each other in shape and structure.

To explain what it means to have a chromosomal map, Fraser puts it like this: Let’s imagine a chromosome as the some 250,000 miles of road in the United Kingdom with each region in the chromosome being a house along these roads. So far, geneticists had been able to assign a number to each home, plotting them in order over 250,000 miles along what looks like just one long road.

But what if that road isn't straight at all, but coiled like a roller coaster squeezed in Godzilla’s grip? That would mean that house number one might neighbor house number 1,000, but be miles and miles from house number 10. If we want to know which houses abut each other, we'll need to have not just the house numbers, but also a map of the road's furls.

Now, let’s put this back in genomic terms. The X chromosome spans more than 153 million base pairs in the human genome, out of about 3.2 billion base pairs (in mice, the X chromosome’s length is about 168 million base pairs). Cramped up, chromosomal regions that would be right next to each other if the chromosome were pulled straight might actually be found tens of thousands of bases apart.

“This is a map of how the chromosome folds, which parts touch and where, and who is next to who,” says Fraser.

Understanding what is connected to what in a chromosome, and where and how it is connected, is critical to understanding how the genome is regulated, which, in turn, is critical to understanding disease and aging, he said.

The X chromosome is a big chromosome – for comparison, the Y chromosome is about 50 million base pairs long – making it a prime candidate for an initial chromosomal model, says Fraser. The other chromosomes, which will be mapped, as well, are expected to also look like blobs of pasta, but to also be as individual, of course, as are different pasta blobs.


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