Basic Genetics for Reputable Breeders: 

     by Dr. Margret L. Casal PhD, Dipl, ECAR   

Dr. Casal has worked on several issues involving the Cavalier including early deafness, cardiology and CM/SM.   She selfishly assists individual breeders working on issues involving genetics.  


2015-09-13 Tiny and his tomato

Mendelian Genetics  - Autosomal dominant inheritance

Gene: Basic Element of heredity that determines traits.  A gene is transmitted from parents to progeny.  

Allele:  Alternative version of a given gene

Locus: Location on a chromosome where a gene with a specific function resides. 

Homozygote:  Pairs of alleles of a given gene are the same.

Heterozygote: Pairs of alleles of a given gene are different.

Genotype: Genetic constitution, internally coded, heritable information, usually only alleles of genes of interest listed

Phenotype: Observable properties of an organism, outward, physical manifestation of the genotype.

In a simple analogy, the genotype can be described as the architectural blueprint and the phenotype as the building that is built from the blueprint.  

One allele of a given gene is enough to determine the phenotype (trait/disease allele D with d being normal) and since the gene is located on the autosome (not sex determining chromosome) the risk to makes and females is equal.  Affected individuals are usually heterozygotes (Dd).  At least one parent is affected, unless the condition is the result of a new mutation.   

A.  Affected x Normal Matings produces 50% affected offspring.  50% of the animals are normal (phenotype) and are homozygous in the normal allele (dd) and 50% of the animals are phenotypically affected are heterozygous for a normal and a trait determining allele (Dd).

                           D           d

                     d  Dd        dd 

                     D  DD     Dd

B.  Affected x Affected matings produce 75% affected offspring.  Only 25% of the offspring are normal  (dd) but 75 are phenotypically affected but genotypical different: 50% are heterozygote (Dd) and 25 are homozygotes (DD).  Double dose of dominant traits often lead to a more severe phenotype that can lead to early morbidity and mortality.  

In autosomal dominant disorders that are either severely deleterious or that would be selected against by breeders, most of the cases observed in a population will represent new mutations.  These will occur as rare sporadic cases with no prior evidence of their occurrence in related animals.  

Autosomal Recessive Inheritance 

An animal has to have two trait determining (disease) alleles to express the phenotype or be affected (rr).  Again both female and male animals are equally affected.  An animal that has one disease allele is phenotypically normal but is called a CARRIER (for the disease allele; Rr)  The normal individual has the RR genotype

A.  Carrier x Normal mating produces 50% Carrier offspring.  100% of the animals are of normal phenotype.  However, 50% of these are homozygous in the normal allele (RR) and 50% of the animals are Carriers (Rr) and thus heterozygous for a normal and a trait determining allele. 

                      R         r

                R   RR     Rr

                 r    Rr       rr 

B.  Carrier x Carrier matings produce 75% phenotypically normal offspring.  However 2/3 of these are Carriers ( Rr, Rr, RR ).  Without specific tests it is often impossible to distinguish the normals from the carriers.  25% of the offspring are affected (rr). 

Autosomal recessive inherited diseases are by far the most common class of single gene disorders in domestic animals.  In affected families, most affected animals are born to clinically normal parnetns that are carriers of a mutant allele that has been inherited from an ancestor that is common to the sire and the dam (some degree of inbreeding is present). It can be as many as 20 generations back.  

 x-Chromosomal Recessive Inheritance 

The gene of inters is located on the x-chomosome: Therefore two copies of the trait determining (disease) allele are necessary in females but only one copy is needed in males for the phenotype to be expressed.  

Affected males are hemizygotes (they only have one X chromosome).  Most affected offspring are males, born of mating between carrier females and normal males.  In such matings, 50% of the sons are affected and 50% of the daughters are carriers.  Affected females only occur as the result of matings between affected males and carrier or affected females.  When the male is the only affected parent, male to male transmission of the condition is never observed. 

A.  Carrier Female XX* x Normal XY Male mating result in 50% of the males being affected (X*Y).  100% of the females and 50% of the males are of a normal phenotype but half of the females are carriers (XX*)

                                      X         X*

                                X   XX     XX*

                                 Y    XY     X*Y

B.  Carrier Female x Affected Male matings (rare) produce 50% affected offspring.  Half of all males are affected (X*Y) and the other half normal (XY); whereas half of all females are carriers (XX*) and the other half affected (X*X*)

In domestic animals, an important feature of X-linked recessive disorders is that in matings of carrier females to normal males, one half of the male offspring will be affected, regardless of whether the male is related to the female.  Thus inbreeding is not a prominent feature in X-linked recessive disorders.  This is in contrast to autosomal recessive inheritance, in which inbreeding is often present, the parents of affected offspring having inherited the mutant gene from ancestors which they share. 

X-Linked Dominant Inheritance 

X-linked dominant traits are more commonly found in females than males (twice as common in rare traits, since females have two chances to receive an X with the mutant allele, while males have only one).  If the mutant allele is lethal to homozygous male embryos, the disorder will be found only in females.  The chief characteristic of X-linked dominant inheritance in families is that affected males transmit the trait to all of their daughters and none of their sons.  Affected females are usually heterozygous and it may bot be possible to distinguish between autosomal dominant and X-linked dominant inheritance from their offspring.  One half of the females and one half of the males will be affected in both cases.  However, this would be the case only when dominance is complete.  That is when the effect in a heterozygous female is found in a form of hereditary renal disease as in Samoyed dogs. 

Complex Modes of Inheritance 

Many diseases that are of great concern to both breeders and veterinarians are caused not by a single gene but by the interaction of several genes.  To make matters more difficult for the breeder and the geneticist, the phenotype (or the appearance of the trait or disease) can often be modified by environmental influences such as nutrition or exercise. 

Genetic Tests 

Molecular Genetic (DNA Based) Tests for Affected and Carrier Animals - DNA based genetic tests identify differences in DNA sequences and are of two different varieties. One type of test, refereed to as a mutation-based test, recognizes disease causing mutations while a second type of test, the linked-polymorphism test, recognizes DNA differences that are near the disease-causing gene and are used to track normal and mutant alleles of that gene through pedigrees.  While there are significant differences between how these two types of tests are developed and how they are used, they both involve the same basic techniques.  

Essentially all DNA based genetic tests are based on the polymerase chain reaction and consequently can be performed using a very small amount of DNA from the animal of interest.  DNA ;based genetic tests have the advantage (over biochemical assays) that DNA is very easy to obtain by fairly non-invasive techniques and is very stable.  Common sources of DNA include: Blood, hair follicles, cheek swabs, semen and skin biopsies.   

Uses of Genetic Testing 

     The more accurate the test, the quicker a disease can be eliminated from the breeding stock.   The parents and relatives can be tested and their use as a breeder established if they are not carriers for the disease.  Alternatively, if we know that a champion dog is a carrier of a specific disease but the dog has all the best qualities for its breed, then we are able to not only test the bitch he is to be bred to ensuring that she is not a carrier, but we can also test the offspring to retain only those for future breeding that are not carriers.  Thus we do not have to loose the desired traits in the champion dog. 

     The practicality of a genetic screening program depends on the following requisites:  Disease must occur in a defined population (family, herd, breed) with sufficient frequency to be of economic or social importance.  The test for the  heterozygote is accurate and affordable.  Culling of heterozygotes does not deplete key genetic resources.  Test and control program should be acceptable to breeders (precede by educational and public relations programs).  Genetic counseling is available to breeders.  Breed society has rules to insure control is based on test results (registries).  

Uses of Genetic Testing

This is probably the most common question posted to the veterinarian by the conscientious breeder when confronted with a puppy with an unusual illness.  What are the chances of it happening again?  What scan be done about it?  First, it is most important to make an accurate diagnosis.  Second, one needs to know if the same disease has been seen in related animals, in the same breed or is known to be a genetic disease in other species.  If any of these statements are true, then one is most likely dealing with a genetic disease.  Or to quote the 'father' of small animal genetics, Dr. Donald Patterson "Everything is inherited until proven otherwise!"  Alternatively, if the same disease has never been seen in the breed and is not known to be inherited in other species, then one may be dealing with a developmental disorder that may have occurred during pregnancy as a result from toxins, malnutrition, medications, and such.  

In summary, a disease has been seen in the breed before or occurs as a genetic disease in another species, it is likely to be genetic in the animal presented to the veterinarian.  If one needs to make an educated guess as to the mode of inheritance, then it helps to have an idea of the biochemical cause of the disease.  Most enzyme deficiencies are autosomal recessive and most structural defects are dominant.  These are just rules of thumb, there are exceptions! 

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©  Linda Baird & Woody Goode 2015