Human chromosomes 9 and 10 completed 27/5/04. By the Wellcome Trust Sanger Institute In two reports published in the 27 May issue of the journal Nature, researchers from the Wellcome Trust Sanger Institute and their collaborators announce the findings of their study of the finished sequence of human chromosomes 9 and 10.

The detailed analyses provide an overview of the chromosome landscape but, more important, identify new genes involved in disease and give a glimpse of our relationship to our nearest living relative, the chimpanzee.

Chromosome 9: The finished sequence of chromosome 9 comprises nearly 110 million letters of DNA code (base-pairs). Using this sequence, the team have identified almost 1200 genes.

Chromosome 9 harbours four genes that can cause sex-reversal, all the human interferon type 1 genes (interferon is important in suppressing cancer development and in resisting virus infection), a gene implicated in neurodegenerative disease (CHAC), as well as a gene (abl) that is involved in 90 per cent of chronic myeloid leukaemia (CML) cases. CML is one of the first cancers for which a treatment has been developed based on understanding the human genome sequence.

Chromosome 10: The team decoded 131 million base-pairs of the chromosome 10 sequence and found 1357 genes. Alterations in 85 of these genes are known to predispose to diseases such as a form of epilepsy (LGI1), obesity (GAD2), and cancer. The finished sequence is an essential tool in both analysing these genes and finding additional ones; there is genetic evidence for type I diabetes, schizophrenia and Alzheimer's disease.

Chromosome 10 offers a remarkable example as to how duplications have both shaped present day genomes and impacted on gene count. Also of interest is the number of genes sharing the same space; 15 per cent of genes on chromosome 10 are found as overlapping pairs: conventionally it is thought that each gene occupies a unique region of DNA sequence.

Comparisons: The two chromosome sequences point to the rich variety in our genome: chromosome 9 is peppered with regions copied from elsewhere in the genome; chromosome 10 is rich in overlapping genes.

When the teams compared human with all available chimpanzee sequence, a large number of differences was found - for chromosome 10, nearly half the differences would alter the protein sequence.

Moreover, nearly 2 per cent of differences would lead to a truncated (and possibly non-functional) protein. Among the changes that appear to be significant are those affecting a gene that plays a role in cognition and behaviour (HTR7) and one involved in development of the embryo (NODAL).

On chromosome 9, genes such as IL11RA, a gene involved in the immune response, and C9orf37 (a gene identified using the newly available finished sequence) showed a significant difference at the sequence level.

Image credit: Wessex Regional Genetics Centre

Further reading

Humphray SJ, et al. (2004) DNA sequence and analysis of human chromosome 9. Nature. 429: 369-74. Abstract

Deloukas P, et al. (2004) The DNA sequence and comparative analysis of human chromosome 10. Nature 429: 375-81 Abstract