With valuable information emerging from the 1000 (human) genomes project and now a proposal for a 10,000 vertebrate genome project, it's well past time to expose to public scrutiny a project I've been spitballing for a while, which I now dub the 10,201 genomes project. Why that? Well, first it's a bigger number than the others. Second, it's 101 squared.
Okay, perhaps my faithful assistant is swaying me, but I still think it's a useful concept, even if for the time being it must remain a gehunden experiment. All kidding aside, the goal would be to sequence the full breadth of caninity with the prime focus on elucidating the genetic machinery of mammalian morphology. In my biological world, that would be more than enough to justify such a project once the price tag comes down to a few million. With some judicious choices, some fascinating genetic influences on complex behaviors might also emerge. And yes, there is a possibility of some of this feeding back to useful medical advances, though one should be honest to say that this is likely to be a long and winding road. It really devalues saying something will impact medicine when we claim every project will do so.
The general concept would be to collect samples from multiple individuals of every known dog breed, paying attention to important variation within breed standards. It would also be valuable to collect well-annotated samples from individuals who are not purebred but exhibit interesting morphology. For example, I've met a number of "labradoodles" (Labrador retriever x poodle) and they exhibit a wide range of sizes, coat colors and other characteristics -- precisely the fodder for such an experiment. In a similar manner, it is said that the same breed from geographically distant breeders may be quite distinct, so it would be valuable to collect individuals from far-and-wide. But going beyond domesticated dogs, it would be useful to sequence all the wild species as well. With genomes at $1K a run, this would make good sense. Of particular interest for a non-dog genome is the case of lines of foxes. which have been bred over just a half century into a very docile line and a second selected for aggressive tendencies.
What realistically could we expect to find? One would expect a novel gene, as is the case with short legged breeds, to leap out. Presumably regions which have undergone selective sweeps would be spottable as well and linkable to traits. A wealth of high-resolution copy number information would certainly emerge.
Is it worth funding? Well, I'm obviously biased. But already the 10,000 vertebrate genome has kicked up some dust from some who are disappointed that the genomics community has not had "an inordinate fondness for beetles" (only one sequenced so far). Genome sequencing is going to get much cheaper, but never "too cheap to meter". De novo projects will always be inherently more expensive due to more extensive informatics requirements -- the first annotation of the genome is highly valuable but requires extensive effort. I too am disappointed that greater sampling of arthropods hasn't been sequenced -- and it's hard to imagine folks in the evo-devo world being fond of this point either.
It's hard for me to argue against sequencing thousands of human germlines to uncover valuable medical information or to sequence tens of thousands of somatic cancer genomes for the same reason. But, even so I'd hate to see that push out funding for filling in more information about the tree of life. Still, do we really need 10,000 vertebrate genomes in the near future or 10,201 dog genomes? If the trade for doing only 5,000 additional vertebrates is doing 5,000 diverse invertebrates, I think that is hard to argue against. Depth vs. breadth will always be a challenging call, but perhaps breadth should be favored a bit more -- at least once I'm funded for my ultra-deep project!
Showing posts with label dogs. Show all posts
Showing posts with label dogs. Show all posts
Thursday, November 12, 2009
Thursday, August 27, 2009
What happened to the eighth dog hair style?
For the second time this summer Science has another step forward in understanding the genetics of dog breeds. Previously it was the identification of a post-wolf event which led to short-legged dogs (which includes my faithful assistant); this time it is that a large (600+ dogs) genetic study has shown that vast majority of dog coat types can be explained by just three genes (you'll need a Science subscription to access these).
Figure 3 of the paper makes the point quite graphically. The three genes found in the study are FGF5, RSPO2 and KRT71. FGF5 is a secreted growth factor previously implicated in hair development, RSPO2 is a regulator of the Wnt pathway known to be important in hair follicles and KRT71 is a keratin which causes a curly phenotype when mutated in mice. So even though these were found by a genome-wide genetic study, they are all excellent candidate genes. Below is my version of Figure 3 (which has illustrations of the dog breeds). Furnishings are extra hair around the eyebrows. Wolf means the ancestral genotype and novel a genotype that post-dates domestication.
Now, this covers a lot of furry ground. The paper claims it describes coat configuration in 95% of the 108 breeds examined. There are some strange coats probably not covered by this work (for example, the Komondor and Puli, which grow dreadlocks -- I haven't seen one personally yet). They do note that a few very long haired breeds (Afghan hound) lack the FGF5 mutation found here, suggesting that some breeds use a different genetic strategy.
The variants themselves are a mix (mutts?). RSPO2 as a mutation in the 3' non-coding region which the paper shows increases expression by about 3 fold. The FGF5 mutation changes a conserved amino acid from Cys to Phe; that Cys may well be involved in a covalent Cys-Cys bond in the structure (common in secreted proteins). The KRT71 mutation is also a coding region mutation.
But the more obvious question to me is they describe 3 essentially binary genetic determinants of coat style -- but describe only 7 combinations not the 8 which could be expected. The missing genotype in the table is wolf-like at FGF5 and RSPO2 but with the novel (post-domestication) genotype at KRT71. Presumably this would yield a short, curly phenotype -- perhaps too short for curling to observed and the trait pair to be selected by breeders.
Cadieu, E., Neff, M., Quignon, P., Walsh, K., Chase, K., Parker, H., VonHoldt, B., Rhue, A., Boyko, A., Byers, A., Wong, A., Mosher, D., Elkahloun, A., Spady, T., Andre, C., Lark, K., Cargill, M., Bustamante, C., Wayne, R., & Ostrander, E. (2009). Coat Variation in the Domestic Dog Is Governed by Variants in Three Genes Science DOI: 10.1126/science.1177808
Figure 3 of the paper makes the point quite graphically. The three genes found in the study are FGF5, RSPO2 and KRT71. FGF5 is a secreted growth factor previously implicated in hair development, RSPO2 is a regulator of the Wnt pathway known to be important in hair follicles and KRT71 is a keratin which causes a curly phenotype when mutated in mice. So even though these were found by a genome-wide genetic study, they are all excellent candidate genes. Below is my version of Figure 3 (which has illustrations of the dog breeds). Furnishings are extra hair around the eyebrows. Wolf means the ancestral genotype and novel a genotype that post-dates domestication.
| Phenotype | Exemplar | FGF5 | RSPO2 | KRT71 |
| Short | Basset hound | wolf | wolf | wolf |
| Wire | Australian terrier | wolf | novel | wolf |
| Wire and Curly | Airedale Terrier | wolf | novel | novel |
| Long | Golden Retriever | novel | wolf | wolf |
| Long with Furnishings | Bearded Collie | novel | novel | wolf |
| Curly | Irish Water Spaniel | novel | wolf | novel |
| Curly with Furnishings | Bichon Frise | novel | novel | novel |
Now, this covers a lot of furry ground. The paper claims it describes coat configuration in 95% of the 108 breeds examined. There are some strange coats probably not covered by this work (for example, the Komondor and Puli, which grow dreadlocks -- I haven't seen one personally yet). They do note that a few very long haired breeds (Afghan hound) lack the FGF5 mutation found here, suggesting that some breeds use a different genetic strategy.
The variants themselves are a mix (mutts?). RSPO2 as a mutation in the 3' non-coding region which the paper shows increases expression by about 3 fold. The FGF5 mutation changes a conserved amino acid from Cys to Phe; that Cys may well be involved in a covalent Cys-Cys bond in the structure (common in secreted proteins). The KRT71 mutation is also a coding region mutation.
But the more obvious question to me is they describe 3 essentially binary genetic determinants of coat style -- but describe only 7 combinations not the 8 which could be expected. The missing genotype in the table is wolf-like at FGF5 and RSPO2 but with the novel (post-domestication) genotype at KRT71. Presumably this would yield a short, curly phenotype -- perhaps too short for curling to observed and the trait pair to be selected by breeders.
Cadieu, E., Neff, M., Quignon, P., Walsh, K., Chase, K., Parker, H., VonHoldt, B., Rhue, A., Boyko, A., Byers, A., Wong, A., Mosher, D., Elkahloun, A., Spady, T., Andre, C., Lark, K., Cargill, M., Bustamante, C., Wayne, R., & Ostrander, E. (2009). Coat Variation in the Domestic Dog Is Governed by Variants in Three Genes Science DOI: 10.1126/science.1177808
Friday, October 19, 2007
What do Harry Potter, Sherlock Holmes, Martha's Vineyard & Science Magazine have in common?
As the Harry Potter series went on, more and more of the characters' names telegraphed a key component of their properties. One of the most blatant of these is Sirius Black, (spoiler alert), who turns out to be capable of transforming into a black dog (Sirius being the dog star). Black dogs show up elsewhere in literature: the hound of the Baskervilles is reported to be a huge black hound. On the Vineyard, there is a restaurant/bar whose apparel has spread around the globe with it's black Labrador log, The Black Dog. Now, joining the parade is Science (currently available in full in the Science Express prepublication section to subscribers only), with the identification of the gene responsible for black coat color, a locus previously known as K.
The new gene turns out to be a beta defensin, a member of a family known previously for its role in immunity. Dogs are unusual in having black driven by a gene other than Mc1R and agouti. Mc1R is a G-protein coupled receptor (GPCRs) and agouti encodes a ligand. Strikingly, beta defensins turn out to be ligands for Mc1R, closing the circle.
GPCRs constitute one of the biggest classes of targets for existing drugs, so one of the first tasks of anyone during the genome gold rush was to identify every GPCR they could. However, it is very difficult to advance a GPCR if it lacks a known ligand ("orphan receptor"), so drug discovery groups spent a lot of effort attempting to 'de-orphan' the GPCRs flowing from the genome project -- and very few had much luck. I haven't kept close tabs on the field for a few years, but it would seem there are still a lot of orphans left. Plus, from a physiological standpoint you don't just want to know 'a' ligand for a receptor but the full complement. This work is a reminder that new GPCR discoveries can come from a largely unanticipated angle.
It's been a huge year for dog genetics, and I've touched on a few items in this space. I suspect that someone really in tune to the field could easily fill a blog with it; I just catch the things in the front-line journals and the occasional stray from a literature or Google search. Much of the work this year has been on morphology, and there's still plenty to do. Many dog breeds have common abnormalities and those are beginning to be unraveled as well -- and many will likely have relevance to human traits. One I stumbled on recently is the identification of a deletion responsible for a common eye defect in collies.
The really big fireworks will come when behavior genetics studies really fire up in dog. Some traits have been deliberately bred into particular breeds (think herding & hunting dogs) and others inadvertently (such as anxiety syndromes). Temperament varies by breed, and of course just about any dog is more docile than their wild lupine relatives. There will be lots of interesting science -- and probably more than a few findings that will be badly reported and misinterpreted in the popular press. Let's hope, for his sake, that James Watson keeps his mouth shut about any of it.
BTW, Lupine? -- another telegraph character name. Fluffy, on the other hand, not quite the name you'd expect on a gigantic three-headed dog. Alas, there's only one Fluffy mentioned, so it might not be possible to map the genes responsible for that!
The new gene turns out to be a beta defensin, a member of a family known previously for its role in immunity. Dogs are unusual in having black driven by a gene other than Mc1R and agouti. Mc1R is a G-protein coupled receptor (GPCRs) and agouti encodes a ligand. Strikingly, beta defensins turn out to be ligands for Mc1R, closing the circle.
GPCRs constitute one of the biggest classes of targets for existing drugs, so one of the first tasks of anyone during the genome gold rush was to identify every GPCR they could. However, it is very difficult to advance a GPCR if it lacks a known ligand ("orphan receptor"), so drug discovery groups spent a lot of effort attempting to 'de-orphan' the GPCRs flowing from the genome project -- and very few had much luck. I haven't kept close tabs on the field for a few years, but it would seem there are still a lot of orphans left. Plus, from a physiological standpoint you don't just want to know 'a' ligand for a receptor but the full complement. This work is a reminder that new GPCR discoveries can come from a largely unanticipated angle.
It's been a huge year for dog genetics, and I've touched on a few items in this space. I suspect that someone really in tune to the field could easily fill a blog with it; I just catch the things in the front-line journals and the occasional stray from a literature or Google search. Much of the work this year has been on morphology, and there's still plenty to do. Many dog breeds have common abnormalities and those are beginning to be unraveled as well -- and many will likely have relevance to human traits. One I stumbled on recently is the identification of a deletion responsible for a common eye defect in collies.
The really big fireworks will come when behavior genetics studies really fire up in dog. Some traits have been deliberately bred into particular breeds (think herding & hunting dogs) and others inadvertently (such as anxiety syndromes). Temperament varies by breed, and of course just about any dog is more docile than their wild lupine relatives. There will be lots of interesting science -- and probably more than a few findings that will be badly reported and misinterpreted in the popular press. Let's hope, for his sake, that James Watson keeps his mouth shut about any of it.
BTW, Lupine? -- another telegraph character name. Fluffy, on the other hand, not quite the name you'd expect on a gigantic three-headed dog. Alas, there's only one Fluffy mentioned, so it might not be possible to map the genes responsible for that!
Monday, October 01, 2007
Spot's Ridges (& Ridge's Spots?)
Miss Amanda is quite excited about two new papers on the Nature Genetics preprint site, though as we don't have a subscription we're stuck reading just the abstracts and the supplementary material. The papers use genetic mapping for fine-scale mapping of the variations responsible for two visible phenotypes: the distinctive back ridge in ridgeback dogs and a coat spotting phenotype found in many breeds.
A particularly striking claim in the one abstract is that this mapping could be accomplished with approximately 20 individuals. This is quite a small number, and would suggest that many mendelian traits in dogs will be rapidly mapped given the modest (by genomics standards) cost of doing an experiment (arrays are already below the $1K/sample mark) I've promised the little miss we can go halfsies on any papers on floppy ears, curled tails or flat faces.
The ridgeback variant is also interesting because it is a copy number variation, a very hot class of genetic variations lately. The duplicated region contains three FGF family members, growth factors known to play roles in development. Of further interest is that the polymorphism also tracks with a nasal abnormality also seen in these dogs. Many pure breeds suffer from distinct maladies which are often direct results of the physical shape of the canine. For example, short snouts raise the risk of eye injury, which is a trauma M.A. suffered soon after arriving at our abode. However, in this case it would appear that the phenotypes have an underlying biological explanation that is not simply that the shape but a common developmental trigger.
This is the time of year for agricultural fairs & I was recently (as usual, biogeek that I am) strolling through one marveling at the range of breeds of various animals. Chickens are perhaps the showiest at these affairs, but there are also lots of varieties of goats, sheep, cows, horses, ducks, rabbits, cavies, etc. Most of these species have draft genomes in one form or another, and with the cost of sequencing sliding down surely all will have one before long. Sequencing a sample of individuals will enable mapping assays to be developed, which is becoming routine. Before long, many of those phenotypic variants, both showy and practical, will be mapped and identified. Other species with many identified breeds, such as cats, goldfish or Darwin's pigeons, will become straightforward to analyze as well.
Dogs do offer the most spectacular gains. This is not just pure boosterism, but just a reflection that dogs seem to have been selected by humans for such a wide variety of traits: shape, color and particularly behavior. I love cats too, but there just aren't any herding breeds!
Dog genetics is also an early example of direct-to-consumer genetic scanning -- one can check up on the breed heritage of a dog. There is a dog up the street which was marketed as a purebred Shih Tzu, but the face is radically different from my companion's. Nothing wrong with that, and it was probably just a bit of confusion at the breeder, though Amanda thinks it is more of an example a Svejk-style skulduggery (I should never have read that stuff to her!).
A particularly striking claim in the one abstract is that this mapping could be accomplished with approximately 20 individuals. This is quite a small number, and would suggest that many mendelian traits in dogs will be rapidly mapped given the modest (by genomics standards) cost of doing an experiment (arrays are already below the $1K/sample mark) I've promised the little miss we can go halfsies on any papers on floppy ears, curled tails or flat faces.
The ridgeback variant is also interesting because it is a copy number variation, a very hot class of genetic variations lately. The duplicated region contains three FGF family members, growth factors known to play roles in development. Of further interest is that the polymorphism also tracks with a nasal abnormality also seen in these dogs. Many pure breeds suffer from distinct maladies which are often direct results of the physical shape of the canine. For example, short snouts raise the risk of eye injury, which is a trauma M.A. suffered soon after arriving at our abode. However, in this case it would appear that the phenotypes have an underlying biological explanation that is not simply that the shape but a common developmental trigger.
This is the time of year for agricultural fairs & I was recently (as usual, biogeek that I am) strolling through one marveling at the range of breeds of various animals. Chickens are perhaps the showiest at these affairs, but there are also lots of varieties of goats, sheep, cows, horses, ducks, rabbits, cavies, etc. Most of these species have draft genomes in one form or another, and with the cost of sequencing sliding down surely all will have one before long. Sequencing a sample of individuals will enable mapping assays to be developed, which is becoming routine. Before long, many of those phenotypic variants, both showy and practical, will be mapped and identified. Other species with many identified breeds, such as cats, goldfish or Darwin's pigeons, will become straightforward to analyze as well.
Dogs do offer the most spectacular gains. This is not just pure boosterism, but just a reflection that dogs seem to have been selected by humans for such a wide variety of traits: shape, color and particularly behavior. I love cats too, but there just aren't any herding breeds!
Dog genetics is also an early example of direct-to-consumer genetic scanning -- one can check up on the breed heritage of a dog. There is a dog up the street which was marketed as a purebred Shih Tzu, but the face is radically different from my companion's. Nothing wrong with that, and it was probably just a bit of confusion at the breeder, though Amanda thinks it is more of an example a Svejk-style skulduggery (I should never have read that stuff to her!).
Friday, May 25, 2007
A little color in our lives
For the general public, all too many reports on genetic phenomena are either very abstract or extremely scary: either it is some phenomenon never before discussed in the popular press or some sort of new risk factor for a dreaded disease. It is nice to see progress on traits which are non-threatening and which can be scored by most individuals. Such visible traits are often used in introductory instruction. While the rare and exotic may be striking, it is far more exciting to discover that science is tackling a trait you see in someone near-and-dear, a trait you see sported on a daily basis. Thanks to the glory of random Medline search noise, I discovered just such a paper (open access!), greatly apropos my dear Amanda.
What the paper found is that explaining the modulation of hair color by two known genes of relevance, Mc1r and agouti, is insufficient. The color pattern known as brindle doesn't fit these results, and they identify a new genetic region (K) responsible for brindling.
Color phenotypes are fun to look at because they are so easy, and because they can often simply illustrate some of the more complex genetic phenomena. A classic example are tortoiseshell and calico cats, which are nearly always female and are due to X-inactivation (I think XXY male cats are viable, and therefore could exhibit these colors). In this case, the various color loci and alleles exhibit epistasis, the hiding (Gr: "stand upon") of the phenotype from one locus due to the genotype at another locus. For example, an Mc1r allele known to encode a truncated (and therefore non-functional) protein prevents any combination of K and agouti alleles from producing a black coat.
Now this is just a mapping paper, and so the gene in question has not been pinpointed. The paper points to there being ~250 genes in the interval in question, with nothing rolling over on first glance. However, they suggest that looking at non-SNP markers, such as simple nucleotide repeats, and additional pedigrees should enable a candidate to be identified.
What will also be interesting, and perhaps not make this discovery quite so benign, is whether variants at this locus affect energy metabolism. Due to some deep evolutionary links (that, alas, I've forgotten the details), coat color mutations often result in weight regulation disorders or severe developmental defects. Both of the other genes mentioned in the paper, Mc1r and Agouti, are important areas for obesity and diabetes research, particularly since Mc1r is in a class of proteins (GPCRs) which has historically been targetable by oral medications. Beige mutant shows both weight and developmental issues, and steel (a grey phenotype) has a host of developmental problems. The brindle phenotype is not known in humans, so it will be interesting to see if (a) the gene is functional in humans (b) has variation across human populations and (c) whether that variation is linked to subtle variations in phenotype
What the paper found is that explaining the modulation of hair color by two known genes of relevance, Mc1r and agouti, is insufficient. The color pattern known as brindle doesn't fit these results, and they identify a new genetic region (K) responsible for brindling.
Color phenotypes are fun to look at because they are so easy, and because they can often simply illustrate some of the more complex genetic phenomena. A classic example are tortoiseshell and calico cats, which are nearly always female and are due to X-inactivation (I think XXY male cats are viable, and therefore could exhibit these colors). In this case, the various color loci and alleles exhibit epistasis, the hiding (Gr: "stand upon") of the phenotype from one locus due to the genotype at another locus. For example, an Mc1r allele known to encode a truncated (and therefore non-functional) protein prevents any combination of K and agouti alleles from producing a black coat.
Now this is just a mapping paper, and so the gene in question has not been pinpointed. The paper points to there being ~250 genes in the interval in question, with nothing rolling over on first glance. However, they suggest that looking at non-SNP markers, such as simple nucleotide repeats, and additional pedigrees should enable a candidate to be identified.
What will also be interesting, and perhaps not make this discovery quite so benign, is whether variants at this locus affect energy metabolism. Due to some deep evolutionary links (that, alas, I've forgotten the details), coat color mutations often result in weight regulation disorders or severe developmental defects. Both of the other genes mentioned in the paper, Mc1r and Agouti, are important areas for obesity and diabetes research, particularly since Mc1r is in a class of proteins (GPCRs) which has historically been targetable by oral medications. Beige mutant shows both weight and developmental issues, and steel (a grey phenotype) has a host of developmental problems. The brindle phenotype is not known in humans, so it will be interesting to see if (a) the gene is functional in humans (b) has variation across human populations and (c) whether that variation is linked to subtle variations in phenotype
Friday, April 06, 2007
woof WOOF!
I had offered to let the Omics! Omics ergonomics director scribe tonight's entry, since it covers a topic of which she has direct knowledge, but we ran into two problems. First, the keyboard is poorly engineered for the configuration of her digits. Second, she's too excited by the news to think straight. But, she did suggest the headline and sometimes that is the hardest part of all.
Dogs are amazing products of human selection. Size, color, shapes of various body parts, and even behaviors are distinctive to particular breeds. The size range of adult dogs exceeds that of any other mammal, as wonderfully illustrated by the
cover of Science, as the issue announces the IGF1 locus as the major determinant of size in dogs.
This paper also illustrates how science can be a bit slow to get off the ground. About 15 years ago I heard a seminar from the senior author of this paper discussing the great promise of dog genetics to shed light on important medical and biological questions. In the meantime, there really haven't been much in the way of splashy dog genetics papers, though the community has been slowly building up a cache of tools. I think it is a reasonable expectation that this paper will be the head end of a series of papers unleashing the promise of the field.
After all, consider my diminutive assistant.
. If you line her up with a Scottish terrier, while they are about the same size they have little else in common in their basic shape. Amanda has the flat face characteristic of her tong (The Ancient and Honourable Order of the Shih Tzu), whereas the Scottie has a distinctive snout which marks his clan. Her tail could honestly mistaken for a feather duster, whereas the terrier's has a less severe curl and isn't fluffy. A Scottie has erect ears; a Shih Tzu's are floppy. Each one of those characters could probably land a paper isolating them in a good journal. Perhaps even more striking would be the identification of a locus leading one of the sterotyped behaviors of a working dog. Half of Dr. Ostrander's seminar 1111 years ago (hey, this is an informatics blog!) was video of border collies herding sheep -- and ever since I can't watch a border collie playing with a frisbee or playing with kids and think of it except in terms of herding.
Many other domesticated animals have a large number of interesting breeds, but never quite as varied as dogs. Dogs were simply bred for more roles than cats, pigs, horses, cows or rabbits -- leading the selection of a wider variety of traits.
Yes, dog genomics promises to dig out some interesting biology, to fetch new insights into the genetics of morphology and behavior. When it comes to the secrets of the mammalian genome, we must not let sleeping dogs lie.
Dogs are amazing products of human selection. Size, color, shapes of various body parts, and even behaviors are distinctive to particular breeds. The size range of adult dogs exceeds that of any other mammal, as wonderfully illustrated by the
cover of Science, as the issue announces the IGF1 locus as the major determinant of size in dogs.
This paper also illustrates how science can be a bit slow to get off the ground. About 15 years ago I heard a seminar from the senior author of this paper discussing the great promise of dog genetics to shed light on important medical and biological questions. In the meantime, there really haven't been much in the way of splashy dog genetics papers, though the community has been slowly building up a cache of tools. I think it is a reasonable expectation that this paper will be the head end of a series of papers unleashing the promise of the field.
After all, consider my diminutive assistant.
. If you line her up with a Scottish terrier, while they are about the same size they have little else in common in their basic shape. Amanda has the flat face characteristic of her tong (The Ancient and Honourable Order of the Shih Tzu), whereas the Scottie has a distinctive snout which marks his clan. Her tail could honestly mistaken for a feather duster, whereas the terrier's has a less severe curl and isn't fluffy. A Scottie has erect ears; a Shih Tzu's are floppy. Each one of those characters could probably land a paper isolating them in a good journal. Perhaps even more striking would be the identification of a locus leading one of the sterotyped behaviors of a working dog. Half of Dr. Ostrander's seminar 1111 years ago (hey, this is an informatics blog!) was video of border collies herding sheep -- and ever since I can't watch a border collie playing with a frisbee or playing with kids and think of it except in terms of herding.Many other domesticated animals have a large number of interesting breeds, but never quite as varied as dogs. Dogs were simply bred for more roles than cats, pigs, horses, cows or rabbits -- leading the selection of a wider variety of traits.
Yes, dog genomics promises to dig out some interesting biology, to fetch new insights into the genetics of morphology and behavior. When it comes to the secrets of the mammalian genome, we must not let sleeping dogs lie.
Monday, January 29, 2007
Who to sequence?
I am optimistic that the price of sequencing a 4Gb (e.g. human) genome will be falling rapidly over the next decade, so that the idea of commissioning a genome sequence with personal funds will not be out of the question. Alternatively, having a genome run may become a popular giveaway, though it may be that only the rich can afford free (note to anyone trying to give me the same gift: I'll wear a barrel before giving up that prize).
The question then becomes: would it be worth it? If I could get my genome sequenced, would I? Undoubtedly there will be a horde of companies offering to help me interpret the results, probably with the slavish devotion to scientific rigor which characterizes the contemporary nutritional supplement industry. Even if I got good advice, would I follow it? I know I should eat better & exercise more; would a 'bad' genotype really give me that gluteus kick I need? I'm not optimistic about that.
If some interesting biology could result, then that might be enough to convince me. But that doesn't seem likely. The family lore would suggest that I am a gemisch of various Northern European clans, which is certainly a type which has already been sequenced and will certainly get heavily sequenced going forward. Nope, nothing terribly exciting there.
My one form of regular exercise is walking; most work days I walk at least 2km in my commute. When I am not walking to work, I am rarely alone. My most common companion on my walks, now there is a genome worth sequencing.
My best friend is from Asian stock and has a significantly restricted bloodline. Her clan is reputed to have originated in Tibet, but it was in the court of the Chinese emperor that they gained fame, for they were royal greeters in the Forbidden City. With that lofty duty came restricted social opportunities, and so the clan stuck to themselves from a reproductive standpoint.
However, with the 20th century came a rejection of the old ways, and being associated with the emperor was no asset. So they tried to hide -- but how could they? Those many generations of non-intermingling had left a genetic footprint -- distinctive facial features, very fine hair, short stature. Despite the difficulty, some of the clan did escape and emigrate to safer parts of the world to start anew.
Now that is a genome worth sequencing! To have a shot at understanding how genetic variation translates into morphologic variation: that I could see springing some dough on. I can see it now, sitting down together with my laptop and poring over the results, trying to ponder which resulted in that distinctive familial face, which leads to the fine hair that knots without provocation, which prevented cartilage formation in her ears, and which puts that marked curl in her tail which wags so furiously when I get home.
The question then becomes: would it be worth it? If I could get my genome sequenced, would I? Undoubtedly there will be a horde of companies offering to help me interpret the results, probably with the slavish devotion to scientific rigor which characterizes the contemporary nutritional supplement industry. Even if I got good advice, would I follow it? I know I should eat better & exercise more; would a 'bad' genotype really give me that gluteus kick I need? I'm not optimistic about that.
If some interesting biology could result, then that might be enough to convince me. But that doesn't seem likely. The family lore would suggest that I am a gemisch of various Northern European clans, which is certainly a type which has already been sequenced and will certainly get heavily sequenced going forward. Nope, nothing terribly exciting there.
My one form of regular exercise is walking; most work days I walk at least 2km in my commute. When I am not walking to work, I am rarely alone. My most common companion on my walks, now there is a genome worth sequencing.
My best friend is from Asian stock and has a significantly restricted bloodline. Her clan is reputed to have originated in Tibet, but it was in the court of the Chinese emperor that they gained fame, for they were royal greeters in the Forbidden City. With that lofty duty came restricted social opportunities, and so the clan stuck to themselves from a reproductive standpoint.
However, with the 20th century came a rejection of the old ways, and being associated with the emperor was no asset. So they tried to hide -- but how could they? Those many generations of non-intermingling had left a genetic footprint -- distinctive facial features, very fine hair, short stature. Despite the difficulty, some of the clan did escape and emigrate to safer parts of the world to start anew.
Now that is a genome worth sequencing! To have a shot at understanding how genetic variation translates into morphologic variation: that I could see springing some dough on. I can see it now, sitting down together with my laptop and poring over the results, trying to ponder which resulted in that distinctive familial face, which leads to the fine hair that knots without provocation, which prevented cartilage formation in her ears, and which puts that marked curl in her tail which wags so furiously when I get home.
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