1. Genetica per Scienze Naturali a.a. 04-05 prof S. Presciuttini Complex gene interactions in coat color The analysis of coat color in mammals is a beautiful example of how different genes cooperate in the determination of overall coat appearance. The mouse is a good mammal for genetic studies because it is small and thus easy to maintain in the laboratory, and because its reproductive cycle is short. The analysis of coat color in mammals is a beautiful example of how different genes cooperate in the determination of overall coat appearance. The mouse is a good mammal for genetic studies because it is small and thus easy to maintain in the laboratory, and because its reproductive cycle is short. It is the best-studied mammal with regard to the genetic determination of coat color. The genetic determination of coat color in other mammals closely parallels that of mice, and for this reason the mouse acts as a model system. We shall look at examples from other mammals as our discussion proceeds. At least five major genes interact to determine the coat color of mice: the genes are A, B, C, D, and S It is the best-studied mammal with regard to the genetic determination of coat color. The genetic determination of coat color in other mammals closely parallels that of mice, and for this reason the mouse acts as a model system. We shall look at examples from other mammals as our discussion proceeds. At least five major genes interact to determine the coat color of mice: the genes are A, B, C, D, and S

2. Genetica per Scienze Naturali a.a. 04-05 prof S. Presciuttini The A gene This gene determines the distribution of pigment in the hair. The wild- type allele A produces a phenotype called agouti. Agouti is an overall grayish color with a brindled, or "salt-and-pepper," appearance. It is a common color of mammals in nature. The effect is caused by a band of yellow on the otherwise dark hair shaft. This gene determines the distribution of pigment in the hair. The wild- type allele A produces a phenotype called agouti. Agouti is an overall grayish color with a brindled, or "salt-and-pepper," appearance. It is a common color of mammals in nature. The effect is caused by a band of yellow on the otherwise dark hair shaft. In the nonagouti phenotype (determined by the allele a), the yellow band is absent, so there is solid dark pigment throughout. The lethal allele A Y, discussed in an earlier section, is another allele of this gene; it makes the entire shaft yellow. Still another allele a t results in a "black-and-tan" effect, a yellow belly with dark pigmentation elsewhere.

3. Genetica per Scienze Naturali a.a. 04-05 prof S. Presciuttini The B gene This gene determines the color of pigment. There are two major alleles, B coding for black pigment and b for brown. The allele B gives the normal agouti color in combination with A but gives solid black with a/a. The genotype A/- ; b/b gives a streaked brown color called cinnamon, and a/a ; b/b gives solid brown. This gene determines the color of pigment. There are two major alleles, B coding for black pigment and b for brown. The allele B gives the normal agouti color in combination with A but gives solid black with a/a. The genotype A/- ; b/b gives a streaked brown color called cinnamon, and a/a ; b/b gives solid brown. In horses, the breeding of domestic lines seems to have eliminated the A allele that determines the agouti phenotype, although certain wild relatives of the horse do have this allele. The color we have called brown in mice is called chestnut in horses, and this phenotype also is recessive to black. In horses, the breeding of domestic lines seems to have eliminated the A allele that determines the agouti phenotype, although certain wild relatives of the horse do have this allele. The color we have called brown in mice is called chestnut in horses, and this phenotype also is recessive to black.

4. Genetica per Scienze Naturali a.a. 04-05 prof S. Presciuttini The C gene The wild-type allele C permits color expression, and the allele c prevents color expression. The c/c constitution is epistatic to the other color genes. The c/c animals are of course albinos. Albinos are common in many mammalian species and have also been reported among birds, snakes, and fish. The wild-type allele C permits color expression, and the allele c prevents color expression. The c/c constitution is epistatic to the other color genes. The c/c animals are of course albinos. Albinos are common in many mammalian species and have also been reported among birds, snakes, and fish. In most cases, the gene codes for the melanin-producing enzyme tyrosinase. In rabbits an allele of this gene, the ch (Himalayan) allele, determines that pigment will be deposited only at the body extremities. In mice the same allele also produces the phenotype called Himalayan, and in cats the same allele produces the phenotype called Siamese. In most cases, the gene codes for the melanin-producing enzyme tyrosinase. In rabbits an allele of this gene, the ch (Himalayan) allele, determines that pigment will be deposited only at the body extremities. In mice the same allele also produces the phenotype called Himalayan, and in cats the same allele produces the phenotype called Siamese. The allele ch can be considered a version of the c allele with heat-sensitive expression. It is only at the colder body extremities that ch is functional and can make pigment. In warm parts of the body it is expressed just like the albino allele c. This allele shows clearly how the expression of an allele depends on the environment. The allele ch can be considered a version of the c allele with heat-sensitive expression. It is only at the colder body extremities that ch is functional and can make pigment. In warm parts of the body it is expressed just like the albino allele c. This allele shows clearly how the expression of an allele depends on the environment.

5. Genetica per Scienze Naturali a.a. 04-05 prof S. Presciuttini The D gene The D gene controls the intensity of pigment specified by the other coat color genes. The genotypes D/D and D/d permit full expression of color in mice, but d/d "dilutes" the color, making it look milky. The effect is due to an uneven distribution of pigment in the hair shaft. Dilute agouti, dilute cinnamon, dilute brown, and dilute black coats all are possible. A gene with such an effect is called a modifier gene. The D gene controls the intensity of pigment specified by the other coat color genes. The genotypes D/D and D/d permit full expression of color in mice, but d/d "dilutes" the color, making it look milky. The effect is due to an uneven distribution of pigment in the hair shaft. Dilute agouti, dilute cinnamon, dilute brown, and dilute black coats all are possible. A gene with such an effect is called a modifier gene. In horses, the D allele shows incomplete dominance. The figure shows how dilution affects the appearance of chestnut and bay horses. Cases of dilution in the coats of house cats also are commonly seen.

6. Genetica per Scienze Naturali a.a. 04-05 prof S. Presciuttini The S gene The S gene controls the distribution of coat pigment throughout the body. In effect, it controls the presence or absence of spots. The genotype S/ results in no spots, and s/s produces a spotting pattern called piebald in both mice and horses. This pattern can be superimposed on any of the coat colors considered so far, with the exception of albino. The S gene controls the distribution of coat pigment throughout the body. In effect, it controls the presence or absence of spots. The genotype S/ results in no spots, and s/s produces a spotting pattern called piebald in both mice and horses. This pattern can be superimposed on any of the coat colors considered so far, with the exception of albino.

7. Genetica per Scienze Naturali a.a. 04-05 prof S. Presciuttini Summary of coat color genetics in mice The normal coat appearance in wild mice is produced by a complex set of interacting genes determining pigment type, pigment distribution in the individual hairs, pigment distribution on the animal's body, and the presence or absence of pigment. Such interactions are deduced from crosses in which two or more of the interacting genes are heterozygous for alleles that modify the normal coat color and pattern. Interacting genes such as those in mice determine most characters in any organism. The normal coat appearance in wild mice is produced by a complex set of interacting genes determining pigment type, pigment distribution in the individual hairs, pigment distribution on the animal's body, and the presence or absence of pigment. Such interactions are deduced from crosses in which two or more of the interacting genes are heterozygous for alleles that modify the normal coat color and pattern. Interacting genes such as those in mice determine most characters in any organism. Some of the pigment patterns in mice.

8. Genetica per Scienze Naturali a.a. 04-05 prof S. Presciuttini Modifier genes Modifier gene action can be based on many different molecular mechanisms. One case involves regulatory genes that bind to the upstream region of the gene near the promoter and affect the level of transcription. Positive regulators increase ("up- regulate") transcription rates, and negative regulators decrease ("down-regulate") transcription rates. Modifier gene action can be based on many different molecular mechanisms. One case involves regulatory genes that bind to the upstream region of the gene near the promoter and affect the level of transcription. Positive regulators increase ("up- regulate") transcription rates, and negative regulators decrease ("down-regulate") transcription rates. As an example, consider the regulation of a gene G. G is the normal allele coding for active protein, whereas g is a null allele (caused by a base-pair substitution) that codes for inactive protein. At an unlinked locus, R codes for a regulatory protein that causes high levels of transcription at the G locus, whereas r yields protein that allows only a basal level. If a dihybrid G/g ; R/r is selfed, a 9:3:4 ratio of protein activity is produced, as follows: As an example, consider the regulation of a gene G. G is the normal allele coding for active protein, whereas g is a null allele (caused by a base-pair substitution) that codes for inactive protein. At an unlinked locus, R codes for a regulatory protein that causes high levels of transcription at the G locus, whereas r yields protein that allows only a basal level. If a dihybrid G/g ; R/r is selfed, a 9:3:4 ratio of protein activity is produced, as follows:

9. Genetica per Scienze Naturali a.a. 04-05 prof S. Presciuttini Penetrance and Expressivity Penetrance is defined as the percentage of individuals with a given genotype who exhibit the phenotype associated with that genotype. For example, an organism may have a particular genotype but may not express the corresponding phenotype because of modifiers, epistatic genes, or suppressors in the rest of the genome or because of a modifying effect of the environment. Alternatively, absence of a gene function may intrinsically have very subtle effects that are difficult to measure in a laboratory situation. Penetrance is defined as the percentage of individuals with a given genotype who exhibit the phenotype associated with that genotype. For example, an organism may have a particular genotype but may not express the corresponding phenotype because of modifiers, epistatic genes, or suppressors in the rest of the genome or because of a modifying effect of the environment. Alternatively, absence of a gene function may intrinsically have very subtle effects that are difficult to measure in a laboratory situation. Another term for describing the range of phenotypic expression is called expressivity. Expressivity measures the extent to which a given genotype is expressed at the phenotypic level. Different degrees of expression in different individuals may be due to variation of the allelic constitution of the rest of the genome or to environmental factors. This figure illustrates the distinction between penetrance and expressivity. Another term for describing the range of phenotypic expression is called expressivity. Expressivity measures the extent to which a given genotype is expressed at the phenotypic level. Different degrees of expression in different individuals may be due to variation of the allelic constitution of the rest of the genome or to environmental factors. This figure illustrates the distinction between penetrance and expressivity.