Although researchers continue to debate the ultimate number of genes that are contained within the human genome, the portion linked to chromosome 21 seemed like a done deal.
Out of the 23 pairs of chromosomes that act as a storage spot for all of our genes, chromosome 21 has been one of the most intensively studied ever since it was discovered that Down syndrome occurs in those who have an extra copy of this chromosome.
An initial DNA sequence of chromosome 21 published two years ago confirmed 127 known genes and another 98 were predicted.
But a new study to appear in the June issue of Genomics suggests that these earlier predictions may be off the mark.
Re-analyzing the same chromosome through a different technique, researchers at the University of Geneva and the Ludwig Institute for Cancer Research found that chromosome 21 contains roughly 10% more genes than were either confirmed or predicted.
“This demonstrates why we cannot rely on gene prediction alone to identify all human genes,” said the study's lead author, Dr. Stylianos Antonarakis, of the Division of Medical Genetics at the University of Geneva Medical School. “Getting the right number of genes is crucial if we hope to use this information to fight disease.”
Chromosome 21 is associated with several other disorders besides Down syndrome, including bipolar disease and certain types of cancer.
Various teams have attempted to calculate genes by assembling small pieces of DNA and then estimating how many of these are situated in a particular chromosome.
In the current study, researchers analyzed chromosome 21 through a strategy that compares the genome sequence with experimental data generated from expressed sequence tags (ESTs). Taken from various tissues or cell types, EST transcripts provide strong evidence that a portion of the genome is actually expressed and can thus be considered a gene.
Scientists at Ludwig have generated a considerable amount of publicly available EST data through a technique they term ORESTES (open reading frames ESTs), which detects genes that are expressed even in very low levels.
After using this approach to locate a number of suspected new genes on chromosome 21, the team ran further tests to ensure that their suspicions proved correct. All told, the researchers identified 163 genes known to exist in chromosome 21 while discovering 19 new ones.
Along with helping to determine the genetic content of chromosome 21, such methods may provide a more accurate count of the entire human genome, which current estimates put anywhere from 21,000 to more than 100,000.
“The initial 'road map' of the human genome has been extraordinarily important for pointing everyone in the right direction, but we are finding a lot of room for errors,” said Dr. Antonarakis. “A more accurate map will require a gene by gene search that needs to be followed up with thorough testing.”
Ludwig Institute for Cancer Research
[Contact: Eric Sabo]