{"id":20885,"date":"2022-06-08T18:52:16","date_gmt":"2022-06-08T18:52:16","guid":{"rendered":"http:\/\/labgenvet.ca\/?page_id=20885"},"modified":"2024-04-12T17:57:30","modified_gmt":"2024-04-12T17:57:30","slug":"cat-genetics-3-0-simple-genetic-diseases","status":"publish","type":"page","link":"https:\/\/labgenvet.ca\/en\/cat-genetics-3-0-simple-genetic-diseases\/","title":{"rendered":"Cat Genetics 3.0: Simple Genetic Diseases"},"content":{"rendered":"

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Cat Genetics 3.0: Simple Genetic Diseases<\/h1>\n

\"\"<\/a>The prevalence of genetic diseases in our cats is a recognized and long-standing problem, and the problem is twofold.\u00a0 First and obviously, we have cats that are sick because of a genetic disease.\u00a0 Secondly and more insidiously, we have cats that are perfectly healthy but who are carriers for the disease-causing mutation.<\/p>\n

These carrier animals can give us sick animals in future generations.\u00a0 We can identify the sick animals relatively easily, however treatments are often limited.\u00a0 Identifying carrier animals is much more of a challenge.\u00a0 And if we want to eliminate genetic diseases from our cat breeds, we have to be able to identify the carrier animals.<\/p>\n

Mutations and Diseases, Old and New<\/h3>\n

\"\"<\/a>Currently there are over 30 genetic diseases described in cats for which the gene and the disease-causing mutation have been identified (for a list and a description \u00a0of these diseases, please see Labgenvet’s Cat Genetic Disease Search<\/a>. For some mutations, the genetic disease is restricted to one breed; these mutations tend to be young (or recent) mutations, occurring after the breed was established, generally within the last 50 to 100 years.\u00a0 An example is Mucopolysaccharidosis VI (MPS VI)<\/a>\u00a0seen within the Siamese breed.<\/p>\n

Other mutations are more widespread, causing a disease that is found in many breeds.\u00a0 These mutations tend to be older (more ancient) mutations, having occurred before or at the beginning of the formation of modern cat breeds.\u00a0 An example is the mutation that causes Pyruvate Kinase Deficiency (PKLR)<\/a>, seen in numerous breeds as well as within the domestic cat population.<\/p>\n

Another example of an older mutation is the one that causes PRA-rdAc (Late-onset Blindness)<\/a>, again seen in numerous breeds.<\/p>\n

Some mutations have occurred naturally within the domestic cat population and, because of the phenotypic novelty that they produce, have been used to generate new cat breeds.\u00a0 Examples of this include mutations causing hairless or reduced hair phenotypes as well as the mutations that are the basis for the Munchkin breed or the Scottish Curl breed of cats. See Osteochondrodysplasia (Scottish Fold)<\/a>.<\/p>\n

The concepts of basic genetics are presented in Labgenvet’s Cat Genetics 1.0: The Basics<\/a>.<\/p>\n

Several concepts are worth reviewing.<\/p>\n

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(N)ormal and (M)utated<\/h4>\n

Several definitions are now required to help us with our understanding of genetic diseases in cats.\u00a0 Let\u2019s use the letter\u00a0N\u00a0to describe the normal, natural, or \u201cwild-type\u201d version of a gene, and the letter\u00a0M\u00a0to describe the mutated version of the gene.\u00a0 Since we have two copies of all of our genes (one from our mother, one from our father), this gives us the following possibilities:<\/p>\n

N\/N<\/strong> Homozygote normal,\u00a0(\u201cwild-type\u201d, \u201cclear\u201d, does not contain the mutation for the phenotype or the disease in question)<\/p>\n

M\/N <\/strong>Heterozygote (carrier, single mutant, one copy of the mutation (M) plus one copy of the normal (N) version of the gene)<\/p>\n

M\/M<\/strong> Homozygote mutated (double mutant, two copies of the mutation)<\/p>\n

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Dominant and Recessive<\/h3>\n

\"\"<\/a>Now we can make some useful generalizations about genetic diseases in cats.\u00a0 Many (but not all) genetic diseases in the cat involve one gene and one mutation.\u00a0 These diseases are said to follow\u00a0simple\u00a0(<\/strong>or\u00a0mendelian) genetics<\/strong>.\u00a0 Most (but not all) simple genetic diseases in cats are caused by\u00a0autosomal recessive mutations<\/strong>.\u00a0 An\u00a0autosomal\u00a0<\/strong>mutation is not linked to the sex chromosomes (X or Y) of the animal, and an autosomal genetic disease will affect both males and females equally.<\/p>\n

Dominant<\/strong>\u00a0and\u00a0recessive<\/strong>\u00a0are terms we can use to describe genetic mutations, traits, or diseases. \u00a0They are like the two sides of the same genetic coin.\u00a0 A dominant genetic trait or disease always reveals itself, while a recessive genetic trait or disease is one that is hidden or masked by the dominant version of DNA, and only reveals itself in the absence of the dominant version of DNA, i.e., in the homozygote mutated (M\/M) state. \u00a0The dominant version of DNA is usually (but not always) the normal (N), non-mutated or wild-type version.<\/p>\n

 <\/p>\n

Dominant Genetic Diseases<\/h3>\n

\"\"<\/a>Dominant and recessive genetic diseases present themselves differently within a population, a pedigree, or a litter.\u00a0 Mutations for\u00a0dominant genetic diseases<\/strong>\u00a0are honest: the phenotype follows the genotype, and what you see is what you get.<\/p>\n

Dominant genetic diseases will affect (on average) half of the kittens in a litter or half of the cats in a pedigree.\u00a0 Generally, the affected animal has one copy of the mutation in question (M\/N) and is in fact also the carrier animal.\u00a0 Double mutant animals (M\/M) for a dominant disease are possible but in general and in normal populations this will be rare.\u00a0 For a dominant genetic disease, one or the other of the parents of an affected animal will also be affected.\u00a0 Dominant diseases will be present in each generation.<\/p>\n

 <\/p>\n

An example pedigree for a dominant genetic disease<\/h3>\n

Pedigree of a dominant genetic disease: Phenotype (What we see)<\/strong><\/p>\n

\"\"<\/a><\/strong><\/p>\n

Pedigree of the dominant genetic disease above: Genotype (the honest genetics behind what we see)<\/strong><\/p>\n

\"\"<\/a><\/strong><\/p>\n

Examples of dominant genetic diseases include the hypertrophic cardiomyopathies seen in the Maine Coon, and in the Ragdoll breeds<\/a> and Polycystic Renal Disease (PKD)<\/a>\u00a0 seen in numerous breeds of cats.<\/p>\n

 <\/p>\n

Recessive Genetic Diseases<\/h3>\n

\"\"<\/a>Mutations for\u00a0recessive genetic diseases<\/strong>\u00a0are not completely honest, such that you do not always see what you are getting.\u00a0 Recessive diseases will affect only a few kittens in a litter or a few cats within a pedigree.\u00a0 Generally, neither of the parents are affected, although both parents are (by definition) carriers for the mutation in question.<\/p>\n

Recessive diseases will skip generations.\u00a0 Carrier animals (M\/N)<\/strong> are said to be\u00a0silent<\/strong>: they are healthy and cannot be distinguished from clear animals (N\/N) by their phenotype.\u00a0 Only the double mutant animals (M\/M)<\/strong> are at risk of having the disease.\u00a0 Recessive diseases are difficult to eliminate from a population without the help of a DNA test to identify the silent carrier animals.<\/p>\n

In general, within our domestic animal species including cats, recessive genetic diseases are more common than dominant genetic diseases.<\/p>\n

An example pedigree for a recessive genetic disease<\/h3>\n

Pedigree of a recessive genetic disease: Phenotype (what we see)<\/strong><\/p>\n

\"\"<\/a><\/strong><\/p>\n

Pedigree of the recessive genetic disease above: Genotype (the not-so-honest genetics and what we don’t see)<\/strong><\/p>\n

\"\"<\/a><\/strong><\/p>\n

Examples of recessive genetic diseases include Pyruvate Kinase Deficiency (PKLR)<\/a> seen in numerous breeds and Alpha Mannosidosis<\/a>\u00a0seen in the Persian breed.<\/p>\n

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Complex Genetics and the Genetic \u201cGrey Zone\u201d<\/h3>\n

\"\"<\/a>It is worth keeping in mind that recessive and dominant are our simplified \u201cblack and white\u201d classifications of genetic situations that can in fact involve nuances of grey.\u00a0 Recessive and dominant are like two sizes of hats, large and small, that are expected to fit all sizes of heads.\u00a0 For some genetic diseases, one or the other of the hats will fit, while for other genetic diseases neither of the hats fit very well.<\/p>\n

We start talking about a dominant or recessive disease that displays \u201cvariable penetrance<\/strong>\u201d.\u00a0 Mutations within additional genes, called \u2018\u2018modifying genes\u2019\u2019 <\/strong>can affect whether or not a mutation known to be associated with disease will actually cause the disease.\u00a0 Multiple genes<\/strong> (and mutations) can be involved in the disease phenotype.\u00a0 The genetics of the disease is no longer black and white but rather multiple shades of grey. The genetics of the disease is no longer simple but is now complex<\/strong>. \u00a0Having said this, the simple classification of dominant and recessive can still be useful as a first approximation, so we will keep using these terms.<\/p>\n

And then there is the environment.\u00a0 If all kittens in a litter are affected by a disease, it is highly unlikely to be genetic in origin, but rather an environmental problem, an infectious disease or a toxicity.\u00a0 And just to complicate things, the environment can and does influence how a genetic disease presents itself.\u00a0 Genetics and the environment are linked.<\/p>\n

Thus, genetic diseases do not always follow simple genetics.\u00a0 Genetics, and genetic diseases, can be complex.\u00a0 Understanding complex genetic diseases remains one of our challenges for today and for the future.<\/p>\n

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Developmental vs Degenerative Genetic Diseases<\/h3>\n

\"\"<\/a>Genetic diseases can also be classified in terms of when they affect the animal.\u00a0\u00a0Developmental\u00a0<\/strong>genetic diseases are often apparent soon after birth or in the young kitten.\u00a0\u00a0Degenerative<\/strong>\u00a0genetic diseases affect the adult animal, either young adult or older animal.<\/p>\n

Genetic diseases that are apparent before the animal is of reproductive age are easier to control and eliminate from a breed because affected animals will not be used for reproduction.\u00a0 Genetic diseases that affect animals later in life, after the reproductive years, are much more difficult to control and eliminate since the bad genetics has often already been passed on to the next generation before the disease becomes apparent.<\/p>\n

Genetic diseases can cause symptoms with a range of severity in the cat, from mild and controllable with medical treatment to severe and life-threatening.\u00a0 Silent carrier animals (M\/N) for recessive genetic diseases are problematic because of the difficulty in identifying them as carrier animals.\u00a0 Carrier animals lead a normal and healthy life but if they are used for breeding, they can pass a copy of the mutation (M) to the next generation.\u00a0 Thankfully the development of DNA testing for specific disease mutations has made the identification of carrier animals much easier today than it has been in the past.<\/p>\n

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Genetic Mutations<\/h3>\n

\"\"<\/a>The nature of mutations deserves a few words.\u00a0 A\u00a0genetic mutation<\/strong>\u00a0refers to a change in the sequence of DNA. \u00a0\u00a0Mutations represent the natural variations found within our DNA that we need in order to survive, adapt and evolve as a species. Mutations combined with natural reproduction allow\u00a0natural selection<\/strong>\u00a0(i.e., \u201csurvival of the fittest\u201d) to occur.<\/p>\n

A\u00a0substitution mutation<\/strong>\u00a0is a mutation involving the simple replacement of one letter for another at one of the 2.5 to 3 billion or so letters in the DNA text that makes up our (or our cat\u2019s) genome.\u00a0 An\u00a0insertion<\/strong>\u00a0(or\u00a0deletion<\/strong>)\u00a0mutation<\/strong>\u00a0is the addition (or deletion) of one or more letters within the text of our DNA.\u00a0 In each case, whether mutation by substitution, insertion or deletion, the DNA text gets changed and no longer tells quite the same story that it used to.\u00a0 The change can be bad, indifferent (neutral) or good for the animal.\u00a0 The bad mutations are more numerous, cause genetic diseases and would spell disaster except for the fact that Mother Nature has kept a genetic \u201cAce\u201d up her sleeve, by giving us two copies of all of our genes.<\/p>\n

Yes, we have two parents for a reason; please refer to Labgenvet’s Cat Genetics 1.0: The Basics<\/a>.\u00a0 And then thank your parents for the genetic endowments they have given you.\u00a0 Now the potential disadvantage of the many bad mutations is outweighed by the potential advantage of the few good ones.\u00a0 Thus, genetic variations are good, as long as we have natural selection.\u00a0 But in domestic animals, we no longer have natural selection.\u00a0 Thankfully, we now have DNA testing for detecting the presence of disease-causing mutations.<\/p>\n

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Knowledge is Power, and Power is Responsibility<\/h3>\n

\"\"<\/a>Our knowledge of the mutational basis of simple genetic diseases in cats is increasing every year.\u00a0 With good, validated DNA tests we now have the power to identify carrier (M\/N) animals<\/strong> easily, quickly and at reasonable cost.\u00a0 We can, in theory, eliminate a simple genetic disease from a given breed within one breeding generation and eliminate the disease-causing mutation within two generations.<\/p>\n

A caveat is that moving too quickly to remove a mutation from a breed may increase the coefficient of inbreeding within the breed (see Labgenvet’s page on: Cat Genetics 4.0: Evolution, Breeds, Breeding Strategies and Inbreeding<\/a>) and thus increase the chances of other genetic problems arising.\u00a0\u00a0 Having said this, we now have considerable knowledge about the causes of genetic diseases within our breeds of cats.\u00a0 Knowledge is power. Power is responsibility.\u00a0 The challenge we now face is to take on the responsibility of eliminating these genetic diseases from our cats and therefore improving the genetic health of our cat breeds.<\/p>\n

\u00a9 2022 David W. Silversides
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[vc_row][vc_column][vc_column_text] Cat Genetics 3.0: Simple Genetic Diseases The prevalence of genetic diseases in our cats is a recognized and long-standing problem, and the problem is twofold.\u00a0 First and obviously, we have cats that are sick because of a genetic disease.\u00a0 Secondly and more insidiously, we have cats that are perfectly healthy but who are carriers…<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"class_list":["post-20885","page","type-page","status-publish","hentry","description-off"],"acf":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/pages\/20885","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/comments?post=20885"}],"version-history":[{"count":37,"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/pages\/20885\/revisions"}],"predecessor-version":[{"id":22979,"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/pages\/20885\/revisions\/22979"}],"wp:attachment":[{"href":"https:\/\/labgenvet.ca\/en\/wp-json\/wp\/v2\/media?parent=20885"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}