Human chromosome 5 completed 15/9/04. By DOE/Joint Genome Institute Four years after publicly revealing the official draft human genetic sequence, researchers have reached the halfway point in dotting the i's and crossing the t's of the genetic sentences describing how to build a human..

The newly finalised chromosome 5 is the 12th chromosome to be completed, with 12 more to go. As the new sequence reveals, this chromosome is a genetic behemoth containing key disease genes and a wealth of information about how humans evolved.

The finalised sequence has been produced by the US Department of Energy Joint Genome Institute in collaboration with colleagues at the Stanford Human Genome Center. The final sequence analysis will be published in the 16 September issue of the journal Nature.

Chromosome 5, the largest to be completed thus far, is made up of 180.9 million genetic letters – the As, Ts, Gs, and Cs that compose the genetic alphabet. Those letters spell out the chromosome's 923 genes, including 66 genes that are known to be involved in human disease. Another 14 diseases seem to be caused by chromosome 5 genes, but they haven't yet been linked to a specific gene.

Other chromosome 5 genes include a cluster that codes for interleukins, molecules that are involved in immune signalling and maturation and are also implicated in asthma.

Hidden in the chromosome 5 sequence are clues to how humans evolved after branching away from chimpanzees. On average, the chromosome is more than 99 per cent similar between chimpanzees and humans, with the greatest similarity found in genes that cause diseases when mutated.

Despite similarities in the overall sequence, the human and chimpanzee chromosomes compared have some structural differences, including one large section that is flipped backwards in humans compared to chimps. Such an inversion makes it impossible for the two chromosomes to pair up when the cell divides to create sperm and eggs. Over time, that incompatibility could have driven a reproductive wedge between the evolving populations.

Moving evolutionarily further away, about one-third of chromosome 5 is similar to a chicken chromosome that determines the chicken's sex, much like the X and Y chromosomes in humans. This finding backs up previous research suggesting that before mammals and birds split 300 million years ago, the sex chromosomes had not yet evolved. After the split, mammals and birds developed their own methods of creating males and females.

One duplicated region on chromosome 5 could eventually help explain how spinal muscular dystrophy is inherited. Researchers had known that deletions in the gene for survival of motor neurons (SMN) caused the disease, but people with the same deletion can have much more or less severe forms of the disease. It turns out that the region contains many duplications and other rearrangements, and varies considerably between people.

With the sequence for this region in hand, researchers can now study how variations in the number of deletions or repetitions influences the severity of the disease.

Adapted from a press release by the DOE Joint Genome Institute.

Image credit: Wessex Regional Genetics Centre

Further reading

Schmutz J. et al. (2004) The DNA sequence and comparative analysis of human chromosome 5. Nature 431, 268-274. Abstract