Number 13 - unlucky for genes?

Latest chromosome analysis reveals the variety in our genome

Ahead of this weekend’s HUGO meeting in Berlin, researchers from the Wellcome Trust Sanger Institute today (Thursday 1 April 2004) describe their studies of human chromosome 13 (published in Nature). 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 results 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 – so-called microRNA genes – which are important in controlling the activity of other genes.

The high-quality sequence consists of more than 95.5 million letters of DNA code. Painstaking study shows that, within that sequence, lie only 633 genes – fewer than on chromosome 22, which is less than half the size of 13.

“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.”

Andy Dunham Leader of the team at The Wellcome Trust Sanger Institute

Ruby Banerjee, Molecular Cytogenetics Group Sanger Institute, Genome Research Limited

Microscope image of human chromosomes, with a region of chromosome 13 (13q34) highlighted with fluorescent dye

So the wilderness of chromosome 13 has revealed a bounty of new and exciting detail. Recently developed tools and databases such as Rfam allowed the team to look deeper into regions that might previously have been thought to be barren – 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 recognized only two years ago. Today, several hundred genes for these RNAs are thought to be present in the human genome.

“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.”

Dr Jane Rogers Head of Sequencing at The Wellcome Trust Sanger Institute

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. The sequence produced at the Sanger Institute can only speed that discovery.

More information

• [Ruby Banerjee, Molecular Cytogenetics Group, Sanger Institute, Genome Research Limited

  

  Microscope image of human chromosomes, with a region of chromosome 13 (13q34) highlighted with fluorescent dye

  About 2-3% of the human genome codes for protein: much of the remainder is repetitive sequence, but some 40% or so is not. Some of this sequence will be important in gene regulation, but we are only just beginning to recognise where these regions may be and develop methods to study the roles that they play in controlling biological function. Comparing sequences of genomes from multiple species (comparative genomics) highlights regions that are conserved: these include genes and possible regulatory sequences.
• Following the sequence of the human genome, new resources have been developed to help researchers investigate the range of genetic signals in genomes. Amongst these are ever-improving databases of RNA and protein families, which help the identification and description of novel genes – a process called annotation.
• Recent results suggest that a class of small genes code for RNA molecules that are not translated into protein, but serve to control the activity of other genes. First clearly described in the worm C. elegans, so-called microRNAs (miRNAs) appear to act most commonly to reduce gene activity. It is only with sequence of entire genomes that this new and important class of molecules has been identified.
• Chromosome 13 is acrocentric – that is the centromere (or ‘waist’) of the chromosome lies near one end, and the chromosome effectively has only one gene-coding arm. The sequence reported in the publication in Nature is some 95,564,076 base-pairs of DNA code, covering 98.3% of the long arm of chromosome 13. It consists of five sections.