New and improved mouse genome sequence helps separate man from mouse
Scientists in Sweden, the UK, and the US have presented a drastically improved version of the complete mouse genome in a landmark study that will allow researchers to more clearly differentiate between human and mouse genes. Their findings, published in the journal PLoS Biology, will help to enhance the utility of the mouse as a model for human disease. According to the authors, the mouse (Mus musculus) enjoys a unique position in the study of genetics and genomics (the study of DNA sequences) and is critical to studying human disease. 'It is both the premier animal model for human disease and development and the mammalian genome against which human DNA, genes and genomes are most frequently compared,' the study reads. It is vitally important that scientists can work with an accurate genome sequence when conducting biomedical research. In 2002, the same team of researchers published a draft sequence of the mouse genome they assembled using Whole Genome Sequence and Assembly (WGSA). Using this knowledge, scientists were able for the first time to compare mouse and human DNA sequences. But the draft genome sequence had 176,000 gaps, and parts of the genome were, it now seems, positioned incorrectly. The team focused its efforts on filling in the gaps and putting everything in the right place. 'Only by accounting for these missing genes could we obtain a comprehensive understanding of the biology that distinguishes these two species,' they write. The researchers now describe a much higher-quality assembly of the mouse genome, called 'Build 36'. It was put together by aligning overlapping individual clones that represent parts of the genome, and it successfully closed more than 175,000 of the draft genome's gaps. The result was an illumination of the genome's architecture, and a more complete picture of the genes that belong to the mouse. The research reveals that there are more genetic differences between the two species than previously thought: humans and mice have four fifths of their genes in common. Understanding these differences will enable researchers to more accurately separate the genes that humans share with mice from those found only in mice. 'In retrospect, our previous picture of the mouse genome was incomplete. Only when all the missing pieces of the genomic puzzle had been filled in did we realise that we had been missing large numbers of genes found only in mice, and not in humans,' said Dr Leo Goodstadt from the Medical Research Council (MRC) Functional Genomics Unit in the UK. According to the new study, the draft assembly was comparatively cheap and easy to produce. Many other genomes have since been sequenced to the same extent. But the cost of finishing the assembly of a genome is 'typically at least four times the cost of generating the draft assemblies using traditional Sanger sequencing,' the study reads. It goes on to say, 'Nonetheless, it is clear from our analysis of the finished mouse genome assembly that draft WGSAs will always poorly reflect lineage-specific biology.' 'These new findings are extremely important in helping us to separate genes that underpin biology that is the same across all mammals from genes that make humans and mice so different from one another,' added Professor Chris Ponting of the University of Oxford in the UK. Dr Deanna Church of the National Center for Biotechnology Information at the US National Institutes of Health said that the newly published mouse genome 'will allow us to dismiss some commonly held misconceptions and, more importantly, to reveal many previously hidden secrets of mouse biology'.
Countries
Sweden, United Kingdom