Dog Genome Published by Researchers at TIGR, TCAG New technique, partial shotgun-genome sequencing at 1.5X coverage (6.22 million reads) of genome, provides a useful, cost-effective way to increase number of large genomes analyzed
Analysis reveals that 650 million base pairs of DNA are shared between dog and humans including fragments of putative orthologs for 18,473 of 24,567 annotated human genes; Data provide necessary tools for identifying many human and dog disease genes
Since not all the dog genome has been sequenced this surely represents a minimum estimate on the percentage of genes held in common. Also, not all human genes have been identified and some of the undiscovered ones might turn out to be shared with dogs as well..
September 25, 2003
Rockville, MD - Researchers at The Institute for Genomic Research (TIGR) and The Center for the Advancement of Genomics (TCAG) have sequenced and analyzed 1.5X coverage of the dog genome. The research, published in the September 26th edition of the journal Science, asserts that a new method of genomic sequencing, partial shotgun sequencing, is a cost-effective and efficient method to sequence and analyze many more large eukaryotic genomes now that there are a number of reference genomes available with which to compare. This important new study was funded by the J. Craig Venter Science Foundation.
The TIGR/TCAG team assembled 6.22 million sequences of dog DNA for nearly 80% coverage of the genome. Comparing the dog sequence data with current drafts of the human and mouse genome sequences showed that the dog lineage was the first to diverge from the common ancestor of the three species and that the human and dog are much more similar to each other at the genetic level than to the mouse. The group also identified 974,400 single nucleotide polymorphisms (SNPs) in the dog. These genetic variations are important in understanding the genes that contribute to diseases and traits among various breeds of dogs.
The identified SNPs are probably only a fraction of the total number of SNPs that dogs have. If humans are a reliable indicator then we can expect that eventually millions of dog SNPs will be found. So, yes, your dog really is unique.
The dog genome sequencing project, led by Ewen Kirkness, Ph.D., investigator at TIGR, revealed that more than 25% or 650 million base pairs of DNA overlap between human and dog. The sequence data was used to identify an equivalent dog gene for 75% of known human genes. In addition to this core set of common genes, the sequence data has revealed several hundred gene families that have expanded or contracted since divergence of the dog lineage from our common ancestor. For example, the dog genome is predicted to encode a much greater diversity of olfactory receptors than we find in human - which may contribute to their keen sense of smell.
"In little more than a decade genomics has advanced greatly and we now have approximately 150 completed genomes, including the human, mouse and fruit fly, in the public domain," said J. Craig Venter, Ph.D., president, TCAG. "With each sequenced genome the level of information gleaned through comparative genomics is invaluable to our understanding of human biology, evolution, and basic science research. Our new method is an efficient and effective way of sequencing that will allow more organisms to be analyzed while still providing significant information."
Most of those 150 completed genomes are for bacteria and other species that have smaller genomes. So that is not as impressive as it first sounds.
Conservation of the dog and human genome sequences is not restricted to genes, but includes an equally large fraction of the genomes for which functions are not yet known. "Understanding why these sequences are so highly conserved in different species after millions of years of divergent evolution is now one of the most important challenges for mammalian biologists," says Kirkness.
Comparing genomes between species is a great way to find active important areas. An area that is conserved across species must not be a junk unused area.
The first rough draft sequence of the dog genome was done using DNA from Craig Venter's standard poodle Shadow. It shows that even though our common ancestor with dogs is more distant we are genetically more similar to dogs than to mice.
The study confirms that, while dogs and wolves diverged from the common ancestor of all mammals long before early humans and mice did, dogs are much more closely related to humans than mice are.
"The wolf line diverged a little earlier, but the mouse is evolving faster," Venter said.
One likely reason for the more rapid divergence is that mice have shorter lifespans and shorter reproductive cycles. So mice have gone thru more generations since they split off than have dogs or humans. Another reason could be that their ecological niches exerted more selective pressures on them.
Because so many people love their doggies a great deal of medical knowledge has been amassed about dogs.
"Dogs enjoy a medical surveillance and clinical literature second only to humans, succumbing to 360 genetic diseases that have human counterparts," comment O'Brien and Murphy. "Dogs have been beneficial for standard pharmaceutical safety assessment and also for ground-breaking gene therapy successes."
Dogs get a lot of the same symptoms for many disorders. Though unfortunately they aren't as good at explaining how they feel.
This study demonstrates the extent to which DNA sequencing technology has become faster.
It is a point echoed by Dr Stephen O'Brien from the US National Cancer Institute: "NHGRI recently estimated that in the next four years, US sequencing centres alone could produce 460 billion bases - the equivalent of 192 dog-sized genomes at [just under the Tigr/TCAG] coverage."
Since there are 4,600 mammalian species we are still some way away from having a complete sequencing library of all mammals. Plus, the genetic variations are as important as the basic sequences and we still do not know what all the genetic variations are for a single species let alone what they all mean.
In about 10 or 20 years the cost of DNA sequencing will fall so far and the speed of DNA sequencing machines will increase so much that the sequencing of a genome will be doable in less than a day. At that point what seems like an amazing accomplishment today will seem pretty commonplace.
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