Thursday, 29 November 2007

How Many Genes in the Human Genome?

New Study from Broad Institute Lowers Human Gene Count to 20,500 Thursday, 29 November 2007 A study published online this week in the Proceedings of the National Academy of Sciences indicates that the number of protein-coding genes in the human genome may be much lower than the current estimate of around 24,500 genes. According to the study, published by Michele Clamp and colleagues at the Broad Institute, human gene catalogue’s such as Ensembl, RefSeq, and Vega include many open reading frames that are actually “random occurrences” rather than protein-coding regions — a finding that cuts the number of protein-coding genes in the genome to around 20,500. The Broad team analyzed ORFs for which there is no evidence of evolutionary conservation with mouse or dog. According to the researchers, it has been “broadly suspected” that many of these ORFs are “functionally meaningless,” but there has been no scientific evidence to prove they are not valid genes. “As a result,” they note in the PNAS paper, “the human gene catalogue has remained in considerable doubt.” Clamp and colleagues developed a method to characterize the properties of putative genes that lack cross-species counterparts. By analyzing these non-conserved ORFs alongside the genomes of two primates, the researchers found that they are neither the result of gene innovation in the primate lineage nor the result of gene loss in mouse or dog. This offers “strong evidence” that these non-conserved ORFs are indeed “spurious,” and should be removed from the gene catalogue’s, according to the paper. The Broad team did acknowledge that the study has “certain limitations” that could impact the final gene count. For example, they note, they did not consider 197 putative genes that lie in regions that were omitted from the finished assembly of the human genome. They concede that it’s likely there are additional protein-coding genes yet to be found, but they believe that “the final total is likely to remain under 21,000.” Reference: Distinguishing protein-coding and noncoding genes in the human genome Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0709013104 ......... ZenMaster


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