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Scientists, breeders, and DNA

6/19/2013

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Although the technical abilities of molecular genetics that allow scientists to identify the genes underlying the inherited diseases of dogs continue to improve at an astonishing rate, the educational resources for breeders have not kept up.  Given the ability to test for the recessive autosomal gene causing a particular disease, over and over again breeders have diligently tested and completely purged the population of not just affected animals but also carriers, doing irreversible damage to the gene pool of the breed.  When there are multiple genes to consider, breeders are left to their own devices to make breeding decisions, which might be appropriate for an individual breeder but damaging for the breed.

Mellersh, in "DNA Testing and Domestic Dogs", gives a thoughtful review of these growing problems for breeders and argues that scientists have a responsibility to make the information they produce more accessible to breeders, and also to place risks and benefits in an appropriate context for a lay audience that might have the best of intentions to do the right thing but lacks the expertise to make those judgements themselves.

Mellersh C 2012 DNA testing and domestic dogs.  Mammalian Genome 23: 109-123.  (pdf)
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Gene for inherited centronuclear myopathy in Great Danes same as in humans

6/14/2013

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Studies of Great Danes with Inherited Myopathy (also called "Central Core Myopathy"), which results in debilitating muscle weakness and wasting, exercise intolerance, and collapse, have identified a defect in the BIN1 gene.  This gene encodes for a protein called amphiphysin 2, which plays a critical role in maintaining the ability of muscles to respond to the nerve signals that result in muscle contraction.  (You can read more about it here.)

Bohm et al 2013 Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy.  PLoS Genet 9(6): e1003430. doi:10.1371/journal.pgen.1003430 (pdf)
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Why black dogs get toe cancer 

6/9/2013

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A study of Standard Poodles, Giant Schnauzers, and Briards found that toe cancer was associated with a copy number variation (CNV) - repeats of a set of nucleotides - in a gene (KITLG) involved in melanocyte development (melanocytes are involved in pigmentation). The repeats have apparently been selected for because they improve intensity of pigmentation, thereby inadvertently increasing the risk of toe cancer in proportion to the copy number. The nine black Giant Schnauzers examined were all homozygous for four copies of the CNV, as were 3 of 4 Briards. Light colored Standard Poodles also carry the risk alleles, but are apparently protected from toe cancer by a mutation in the MC1R locus (melanocortin 1 receptor), which is also involved in pigmentation. The challenge now will be to assess the frequency of copy number variants in the breed using population genetics and genome screening, then devise breeding strategies that will reduce risk without adversely affecting genetic diversity.

Other breeds at highest risk for this type of aggressive cancer include the Gordon Setter and Kerry Blue Terrier. (download pdf)

Karyadi DM, Karlins E, Decker B, vonHoldt BM, Carpintero-Ramirez G, et al. (2013) A Copy Number Variant at the KITLG Locus Likely Confers Risk for Canine Squamous Cell Carcinoma of the Digit. PLoS Genet 9(3): e1003409. doi:10.1371/journal.pgen.1003409

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Mutation associated with spinocerebellar ataxia in Parson Russell terriers

6/8/2013

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ABSTRACT
Spinocerebellar ataxia (SCA) in the Parson Russell Terrier (PRT) dog breed is a disease of progressive incoordination of gait and loss of balance. Clinical signs usually become notable between 6 and 12 months of age with affected dogs presenting with symmetric spinocerebellar ataxia particularly evident in the pelvic limbs. The degree of truncal ataxia, pelvic limb hypermetria and impaired balance is progressive, particularly during the initial months of disease. A certain degree of stabilisation as well as intermittent worsening may occur. At the later stages of the disease ambulation often becomes difficult, with owners often electing to euthanise affected dogs on welfare grounds. Using a GWAS approach and target-enriched massively-parallel sequencing, a strongly associated non-synonymous SNP in the CAPN1gene, encoding the calcium dependent cysteine protease calpain1 (mu-calpain), was identified. The SNP is a missense mutation causing a cysteine to tyrosine substitution at residue 115 of the CAPN1 protein. Cysteine 115 is a highly conserved residue and forms a key part of a catalytic triad of amino acids that are crucial to the enzymatic activity of cysteine proteases. The CAPN1 gene shows high levels of expression in the brain and nervous system and roles for the protein in both neuronal necrosis and maintenance have been suggested. Given the functional implications and high level of conservation observed across species, the CAPN1variant represents a provocative candidate for the cause of SCA in the PRT and a novel potential cause of ataxia in humans.

Forman OP, De Risio L, Mellersh CS (2013) Missense Mutation in CAPN1 Is Associated with Spinocerebellar Ataxia in the Parson Russell Terrier Dog Breed. PLoS ONE 8(5): e64627. doi:10.1371/journal.pone.0064627  
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The (molecular) genetics of coat color

5/31/2013

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The genetics of coat color in dogs and cat are complicated but fascinating.  This new publication is an excellent review that discusses not only the genes but the cellular and molecular mechanisms involved.  This will be a very valuable read for anybody who needs to understand the inheritance of pigmentation in dogs (and cats).  You can download a pdf copy here.


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Genetic disorders in pure and mixed-breed dogs

5/29/2013

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Are mixed-breed dogs healthier than purebreds?  Not really, say researchers at UC Davis.  There are differences, however, in the disorders that are most common in each group, and the list for purebreds is a bit longer. Purebreds suffer from aortic stenosis, cardiomyopathy, hypothyroidism, elbow dysplasia, allergic dermatitis, cataracts, epilepsy, and portosystemic shunt, among others.  Mixed-breed dogs are prone to cruciate ligament rupture.  But a long list of genetic disorders are found with equal frequency in both mixed and purebred dogs, including a variety of cancers, hypertrophic cardiomyopathy and a number of other cardiac disorders, hip dysplasia, several endocrine disorders, and lens luxation. (more)

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5/18/2013

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Gene therapy cures Type I diabetes in Beagles
Dogs can also suffer from Type 1 diabetes, in which the pancreas is damaged by an inappropriate immune response and no longer produces insulin.  Just as for humans, the blood sugar of the dog must be monitored and insulin injected daily. Researchers working with diabetic beagles have been able to inject into a muscle the DNA that codes for the production of both insulin and glucokinase (an enzyme critical for blood sugar metabolism).  After a single treatment, blood sugar levels of the dogs normalized, they recovered body weight, and they remained healthy more than 4 years after gene transfer.  (more...)


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5/17/2013

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Genes for skin disorder identified

Humans and dogs are both affected by the allergic skin disease atopic dermatitis (AD), caused by an interaction between genetic and environmental factors. TheGerman shepherd dog (GSD) is a high-risk breed for canine AD (CAD), and they are also affected by low serum IgA levels. A Swedish cohort of GSDs was used to identify a the gene, plakophilin 2 (PKP2), known to be important for skin structure. The researchers also detected a division of the GSD breed into two subpopulations, where one is more prone to develop CAD and to have lower serum IgA levels compared with the other.  (read more) (PLoS Genetics 2013: 9(5): e1003475)

DOGSLIFE: Taking a long view on dog health

DogsLife
Dogslife is the first large-scale internet-based longitudinal study of canine health. The study has been designed to examine how environmental and genetic factors influence the health and development of a birth cohort of UK-based pedigree Labrador Retrievers.  The study currently has 3538 dogs enrolled.  (BMC Veterinary Research 2013: 9:13)


Give that dog a cookie
Wolves are truly carnivores, but it turns out the dog's fondness for cookies might have played a role in domestication.  Researchers comparing the genomes of wolves and 14 breeds of dogs have found that dogs have a surprising number of genes that have to do with processing carbohydrates.  This might have allowed dogs to take advantage of grain-based food scraps discarded by humans and encouraged them to stick around. (listen to the podcast)  (read more)

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5/16/2013

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The gene for dwarfism in Miniature Poodles has a singular ancestral origin

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Miniature Poodles can suffer from a dwarfism that affects both the limb bones and the spinal cord and ribs.   The gene associated with this defect is apparently a single ancestral mutation that is inherited as an autosomal recessive and now occurs in the US population with a carrier frequency of about 10%.  A DNA test has been developed that will enable breeders to avoid producing affected dogs.  (PLoS ONE 7(12): e51917)


Dogs and humans fighting cancer together

Chemotherapy that works for humans frequently also works for dogs because their cancers are nearly identical.  Now, dogs are helping oncologists find new treatments for humans by participating in clinical trials of new drugs.  For dogs and people, it's a win-win.  (more...)

A dog's eye view of morphological diversity  

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The history of genetic discovery offers a lesson in inspired choices.  Mendel pried the principles of inheritance from the seeds, pods, and flowers of pea plants.  Morgan linked trait inheritance to specific chromosomes after the unexpected appearance of a white-eyed fly among the red-eyed multitudes.  McClintock showed that genes could change position on a chromosome by charting the idiosyncrasies of every leaf and kernal of her beloved maize plants.

And now Elaine Ostrander, who admits a sense of "awe" and "marvel" at her pet organism, the domestic dog, has found that some complex traits may not have such a complex genetic basis after all.  Working with longtime collaborators Carlos Bustamante and Robert Wayne, Ostrander and her colleagues report that complex traits like body size and coat color may fall under the control of surprisingly few genes.  (PloS Biol 8(8): e1000452)


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5/15/2013

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Wolf-dog hybrids buck the trend

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Dogs and wolves are the same species - Canis lupus - and can hybridize easily.  Populations of wolves are declining in many places around the world, and there is increasing concern that where wolves live near humans and their dogs, hybridization will deleteriously affect the genome of the wild wolf populations.   Hybridization invariably involves a female wolf and a male dog.  By analyzing the Y chromosome, which is inherited only from the father, and mitochondrial DNA (which is inherited only from the mother), scientists have now found evidence for the first time of mating between male wolves and female dogs.  (PLoS ONE 7(10): e46465)

The nose knows: twins can't fool a dog

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Having an identical twin that you can blame misdeeds on might fool your mother, but not a dog.  German Shepherd dogs trained in scent discrimination by the Czech Republic police force can reliably distinguish between identical twins.  It is thought that the ability to tell individuals apart by odor, and even to recognize kin, was related to the genes for the immune system, called Major Histocompatibility Complex (MHC).  But even though identical twins have identical MHC genes, dogs can still tell them apart.  What the dogs are able to detect is anybody's guess.  (PLoS ONE 6(6): e20704) 


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