Secrets of chromosome 13 revealed

Thursday, 17 June, 2004

Researchers have completed the sequencing of human chromosome 13 - with some surprising results. Among the genes identified using the sequence of chromosome 13 are those that can dispose to breast cancer (BRCA2) as well as regions associated with schizophrenia and one containing a gene implicated in asthma.

One of the most remarkable findings of the research - by the Wellcome Trust Sanger Institute, published in the journal Nature - is just how few genes there are on chromosome 13. Although, for the first time, researchers have used methods to predict the locations of a class of genes - microRNA genes - that are important in controlling the activity of other genes.

The high-quality sequence produced at the institute consists of more than 95.5 million letters of DNA (deoxyribonucleic acid) code. Painstaking study shows that, within that sequence, lie only 633 genes - fewer than on chromosome 22 that is less than half the size of 13.

Andy Dunham, team leader at the Wellcome Trust Sanger Institute, said: "Chromosome 13 has a dramatic genomic landscape, in the centre of which is a huge 'desert' of only 47 genes. Normally, we would expect about 180 genes in such a region of DNA.

"But what we have been able to do is look in greater detail at regions of the chromosome that may control gene activity. We have a clear image of regions that do not code for genes but are shared with other species, and it is clear that some of these will encode regulatory messages."

Therefore, the wilderness of chromosome 13 has revealed a bounty of exciting detail. Recently developed tools and databases such as Rfam (an RNA family database) allowed the team to look deeper into regions that might previously have been thought to be barren - the so-called "junk DNA".

MicroRNAs do not specify proteins but bind to other RNAs and diminish their activity or even lead to their destruction. This is a level of control of genetic activity that was not widely recognised only two years ago. Today, several hundred genes for these RNAs are thought to be present in the human genome.

Dr Jane Rogers, head of sequencing at the Wellcome Trust Sanger Institute, said: "Each chromosome brings its own surprises. Our genome is not a homogeneous whole but a rich mixture of DNA sequences that are revealing new glimpses of how we control our genes and how our genome evolved to look the way it does. High-quality finished sequence and accurate gene analysis help us to pick apart the mysteries of what the large non-coding regions of our genome might do."

She emphasised that much remains to be uncovered: there are regions on chromosome 13 that appear to play an important role in leukaemias and lymphomas but the genes involved have not been identified thus far. But the sequence produced at the Sanger should help speed that discovery.

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