Largest bite at the human genome

Wellcome Trust Sanger Institute doubles gene count on chromosome 6

Wellcome Trust Sanger Institute doubles gene count on chromosome 6
Is there a most valuable part of the human genome? Many corners could be argued, but a strong case can be made for part of chromosome 6, the complete sequence of which is published today by researchers from the Wellcome Trust Sanger Institute in the journal Nature. Chromosome 6, weighing in at more than 166 million chemical letters, or bases, of DNA, is the largest to be fully analysed to date.

Chromosome 6 was already known to include genes with implications for cancer, heart disease and mental health. The team more than doubled the number of genes accurately identified on the chromosome through painstaking analysis, base by base, evidence by evidence.

“This is a superb culmination of eight years’ work to sequence and analyse the largest chromosome to date. The complete catalogue of accurately predicted genes on chromosome 6, freely released, will speed understanding of complex diseases such as diabetes, cancer and heart disease.”

Andrew Mungall Project Leader on chromosome 6

But the most gene-rich and the most variable part of the genome is that of the MHC – the major histocompatability complex. The MHC plays a crucial role in our immune system – our biological defence against microbes — as well as in transplant biology, determining our match against potential donors.

“Chromosome 6 contains the ‘holy grail’ of immunology, the MHC, which helps discriminate between our own cells and those of ‘invaders’, such as bacteria. If this delicate balance is disturbed it can result in autoimmune disease such as type 1 diabetes, rheumatoid arthritis and multiple sclerosis. Autoimmunity is common, complex and affects about 4% of the population. The sequence of chromosome 6 will help to advance research into these human diseases.”

Stephan Beck Immunologist and Head of Human Sequencing at the Wellcome Trust Sanger Institute

Already the sequence has been used to spur new studies that were not previously possible. Because the sequence has been so well analysed, researchers can look for changes in genetic code or deletion of code that predispose to disease. Among such projects is a large-scale analysis to find genes affected in astrocytic glioma, a common form of brain tumour.

“About 50% of brain tumours are of a type called astrocytic glioma. The sequence, analysis and DNA fragments from chromosome 6 provide an invaluable tool for our large-scale study of deletions of genes in glioma patients. The deletions can be directly linked back to the sequence and its features, and therefore provides a new and powerful tool in the search for the genetic changes that result in these cancers.”

Dr Koichi Ichimura Senior Research Associate of the Department of Pathology, University of Cambridge

The finished sequence of chromosome comprises 166,880,988 base-pairs: the entire sequence has been subjected to high-quality manual ‘annotation’, and the team has identified 1557 genes (785 were unknown) and 633 ‘dead’ genes (pseudogenes). The predictions are supported by using, for the first time in a published report, the sequences of five other organisms (mouse, rat and three species of fish).

Press release updated on 12 August 2010 to change link destinations to the new locations for their respective resources.

More information

The chromosome in outline

  • Chromosome 6 sequence is 166,880,988 base-pairs – equivalent to about 50 bacterial genomes
  • Contains 1557 genes
  • Less than 50% of genes on chromosome 6 were known before
  • The most variable human gene – HLA-B – is on chromosome 6. It is involved in immunity
  • Chromosome 6 has three ‘hot spots’ for genetic activity. These appear to serve the protein-making machinery of the cell
  • More than 130,000 sequence variants (SNPs) identified during the project. Some SNPs are important for disease and diagnosis

The Wellcome Trust and Its Founder

The Wellcome Trust is the most diverse biomedical research charity in the world, spending about £450 million every year both in the UK and internationally to support and promote research that will improve the health of humans and animals. The Trust was established under the will of Sir Henry Wellcome, and is funded from a private endowment, which is managed with long-term stability and growth in mind.