Scientists analyse chromosomes 2 and 4 6/4/05. By the National Human Genome Research Institute Detailed analysis of chromosomes 2 and 4 detects the largest 'gene deserts' known in the human genome and uncovers more evidence that human chromosome 2 arose from the fusion of two ancestral ape chromosomes.

In a study published in the April 7 issue of the journal Nature, a multi-institution team, led by Washington University School of Medicine in St Louis, described its analysis of the high-quality reference sequence of chromosomes 2 and 4.

Chromosome 4 has long been of interest to the medical community because it holds the gene for Huntington's disease, polycystic kidney disease, a form of muscular dystrophy and a variety of other inherited disorders. Chromosome 2 is noteworthy for being the second largest human chromosome, trailing only chromosome 1 in size. It is also home to the gene with the longest known, protein-coding sequence: a 280 000 base pair gene that codes for a muscle protein called titin, which is 33 000 amino acids long.

The new analysis confirmed the existence of 1346 protein-coding genes on chromosome 2 and 796 protein-coding genes on chromosome 4. As part of their examination of chromosome 4, the researchers found what are believed to be the largest 'gene deserts' yet discovered in the human genome sequence. These regions of the genome are devoid of protein-coding genes, but researchers suspect that they are important to human biology because they have been conserved throughout the evolution of mammals and birds. Work is now underway to figure out the exact function of these regions.

Humans have 23 pairs of chromosomes – one fewer pair than chimpanzees, gorillas, orang-utans and other great apes. For more than 20 years, researchers have thought human chromosome 2 was produced as the result of the fusion of two mid-sized ape chromosomes, and a Seattle group located the fusion site in 2002. The researchers have now found a 36 000 base pair stretch of the chromosome's DNA sequence that appears to be the relic of the centre (centromere) of the ape chromosome that was inactivated upon fusion with the other.

In another intriguing finding, the researchers identified a messenger RNA (mRNA) transcript from a gene on chromosome 2 that may produce a protein unique to humans and chimps. Scientists have tentative evidence that the gene may be used to make a protein in the brain and the testes.

Adapted from a press release by the National Human Genome Research Institute .

Links

Hillier LW, et al. (2005) Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature 434: 724-31. Abstract