ANSC lecture 2

ANSC 313: Single Gene Inheritance

Heterozygote Phenotypes

  • Overview: Heterozygotes can express phenotypes that differ from both homozygotes. Two key expressions of heterozygosity are codominance and incomplete dominance.

Codominance

  • Definition: Both phenotypes are expressed together but observed separately.

    • Example: In Shorthorn cattle, a roan coat color displays both red and white hairs simultaneously.

    • Genotypes:

      • C^RC^R= red

      • C^RC^W= roan

      • C^WC^W= white

Incomplete Dominance

  • Definition: Heterozygotes show a blended phenotype of both homozygotes.

    • Example: In horses, a cream dilution results from a mutation in the MATP gene:

    • Genotypes:

      • CC= sorrel/chestnut

      • Cc= palomino

      • cc= cremello

Incomplete Dominance and Codominance

  • Visual Example:

    • Parents: RR imes rr

    • Offspring: Both offspring are heterozygous (Rr).

Autosomal Recessive – Generalizations

  • Common Traits:

    • Most are related to enzyme deficiencies

      • individuals can function with one working copy.

    • Phenotypes are generally consistent

      • lacking variable expressivity or reduced penetrance.

    • Symptoms of autosomal recessive conditions are often severe,

    • consanguinity: breeding a close kinship group can increase the likelihood of offspring inheriting two copies of a recessive gene. This can lead to a higher prevalence of autosomal recessive disorders in certain populations.

      • i.e. inbreeding

Phenotype Assumptions

  • It might be assumed recessive if neither parent exhibits the condition

    • other genetic factors could influence expression.

  • Proof of a recessive trait can be derived from recessive x recessive matings

    • Should give a 100% recessive offspring ratio

    • often not possible due to severity

Examples of Autosomal Recessive Conditions

  • Enzyme Deficiencies:

  • inborn errors of metabolism

  • carriers (heterozygotes) often have lower enzyme activity \

  • ex. in cattle:

    • Brahma: Pompe Disease

    • Angus: α-Mannosidosis

Consistent Phenotypes in Families

  • Neuropathic Hydrocephalus in Angus Cattle:

    • Also known as "water head" where calves are born near term with enlarged skulls filled with fluid and no brain present.

  • Exception: Von Willebrand disease, a blood clotting disorder with variable expression attributed to the levels of von Willebrand factor.

Clinical Implications

  • Severity of Symptoms:

    • Symptoms typically manifest at birth or shortly after, often lethal if untreated (e.g., phenylketonuria, PKU).

    • PKU requires a strict diet low in phenylalanine; new medications are available to aid metabolism of this amino acid.

Consanguinity Concerns

  • Relatedness and shared blood (‘consanguinity’) frequently appears in conditions linked to inbreeding or linebreeding.

Autosomal Recessive – Practical Implications

  • Decisions on affected homozygote culling raise ethical questions regarding the treatment of obligate carriers.

  • Carriers: Approximately 2/3 of unaffected siblings may be carriers. This raises the question of whether to cull these siblings as well.

  • Genotype Ratio:

    • The expected 1:2:1 ratio suggests:

    • 1/3 of unaffected are non-carriers

    • 2/3 of unaffected are carriers

Importance of Carrier Detection Testing

  • Essential for accurate genetic management in breeding due to the prevalence of hidden carriers.

Carrier Detection Tests

Categories of Tests

  • Breeding Tests: Mating strategies to identify carriers by the phenotype of affected offspring.

    • mate a sire of interest to either affected of heterozygous carrier. If any affected offspring are born, sire is a carrier

  • Direct Tests: Identify the mutation or biochemical activity through:

    • Biochemical tests (e.g., enzyme levels)

    • DNA testing for specific mutations

    • good if you know/suspect the cause

  • Indirect Tests:

    • When you don’t know the cause

    • Utilize DNA linkage tests for known markers associated with traits

Examples of Breeding Tests

  • Cattle Example:

    • In a scenario where the polled trait is dominant and horned is recessive

    • PP= polled

    • Pp= polled

    • pp= horned

    • Mating a polled bull to a horned cow results in offspring that define the carrier status of the bull. If all offspring are polled, there is a 99% chance the sire is homozygous dominant (PP).

Biochemical Direct Tests

  • tests for the level of activity of an enzyme

  • Genotype Enzyme Activity Correlation (B-mannosidosis in cattle):

    • Genotype determines enzymatic outcome:

    • Homozygous Normal (BB): 100% enzyme activity

    • Heterozygote (Bb): 50% enzyme activity

    • Affected (bb): 0% enzyme activity

  • Not all animals give definitive results (intermediate zone where we cannot say with confidence whether animal is a carrier or not)

DNA Direct Tests

  • Conducted to identify specific mutations responsible for disease traits.

  • Sample collection options include:

    • Hair roots (tail hair), buccal swabs, blood samples, or semen straws.

DNA Tests are available to test for diseases as well as production traits

Indirect Tests – DNA Linkage

  • Used when the exact mutation is unknown

  • Tests for markers linked to the trait.

    • located near the mutation

    • segregates with the mutation

  • Less accurate than direct methods due to potential recombination effects

    • The farther a marker is from the mutation, the greater the change of recombination