Non-Mendelian Genetics Notes

Non-Mendelian Genetics

Mendel's Postulates/Hypothesis Regarding Heredity

Mendel's Four Postulates and Laws of Inheritance:

  • Principle of Paired Factors: Genes exist in pairs.

  • Principle of Dominance: In a heterozygote, one allele may mask the effect of another.

  • Law of Segregation (or Law of Purity of Gametes): Allele pairs separate during gamete formation. (Mendel's First Law of Inheritance)

  • Law of Independent Assortment: Alleles of different genes assort independently of one another during gamete formation. (Mendel's Second Law of Inheritance)

Extensions of Mendelian Genetics

Extensions Include:

  • Incomplete Dominance

  • Codominance

  • Multiple Alleles

  • Multiple Genes

  • Sex-limited traits

  • Sex-influenced traits

  • Sex-linked traits

Assumptions of Mendelian Inheritance

  • Traits: Traits are determined by genes, which exist in two alternative allelic forms

  • Complete Dominance: One allele completely masks the effect of the other.

  • Alleles are found on autosomes: Genes are located on non-sex chromosomes.

  • No Gene Interaction: Genes act independently of one another.

  • Complete Penetrance: The trait is fully expressed when the genotype is present.

Incomplete Dominance

  • Definition: A form of inheritance in which heterozygotes have a phenotype that is intermediate between the phenotypes of the two homozygous parents.

  • Example: Snapdragon flower color

    • R¹R¹ = red

    • R²R² = white

    • R¹R² = pink (F1 generation)

    • F1 x F1 (R¹R² x R¹R²) leads to:

      • 1/4 R¹R¹ red

      • 1/2 R¹R² pink

      • 1/4 R²R² white

  • Interpretation of Lack of Dominance:

    • Consider gene expressions quantitatively and observe gene products carefully.

    • Wild-type allele (R¹) produces an enzyme that synthesizes red pigment.

    • Mutant allele (R²) produces a non-functional enzyme.

    • Heterozygotes produce half the pigment of red flowers, resulting in a pink phenotype.

  • Example: Tay-Sachs Disease

    • Homozygous recessive individuals are severely affected by a fatal lipid-storage disorder.

    • Hexosaminidase A, an enzyme involved in lipid metabolism, has almost no activity.

    • Heterozygotes are phenotypically normal but have about 50% of the enzyme activity of normal individuals, which is sufficient for normal biochemical function.

Codominance

  • Definition: The influence of both alleles in a heterozygote is clearly evident.

  • Example: MN blood group

    • A glycoprotein molecule on the surface of red blood cells acts as a native antigen for biochemical and immunological identity.

    • M and N are controlled by a locus on chromosome 4.

  • Example: Roan cattle

    • RR = Red

    • RWRW = White

    • RRW = Roan (mix of red and white hairs)

A and B Antigens

  • Glycolipids with carbohydrate groups bound to lipid molecules protruding from the RBC membrane.

  • Specificity is based on the terminal sugar of the carbohydrate group.

  • H substance is the precursor where one or two terminal sugars are added.

Sickle-Cell Anemia

  • The gene affects hemoglobin, which transports oxygen.

  • There is incomplete dominance in terms of blood cell shape and codominance in the A and S forms of hemoglobin.

  • The type of dominance inferred depends on the phenotypic level: organismal, cellular, or molecular.

Multiple Alleles

  • When three or more alleles of the same gene are present in a population, the resulting mode of inheritance may be unique.

  • Studies are typically conducted in populations.

  • Number of possible genotypes = \frac{1}{2}n(n+1)

  • Example: ABO blood groups (K. Landsteiner)

    • A and B antigens are present on the surface of RBCs, controlled by a gene on chromosome 9.

    • The I designation stands for isoagglutinogen, another term for antigen.

Bombay Phenotype

  • A rare recessive mutation in the FUT1 gene (fucosyl transferase) prevents the synthesis of complete H substance.

  • An example is a woman in Bombay who was genetically type B but functionally type O.

Lethal Alleles

  • Recessive lethal allele: The wild-type allele is sufficient to produce enough of an essential product for survival in heterozygotes.

    • Example: Yellow coat in mice.

      • The mutant yellow allele is dominant to the wild-type agouti allele, so heterozygous mice have yellow coats.

      • The yellow allele is also a homozygous recessive lethal.

  • Dominant lethal allele: The presence of just one copy of the allele results in the death of the individual.

    • Example: Huntington's disease.

      • The disease in heterozygotes is delayed until adulthood (around age 40).

      • Affected individuals undergo gradual nervous and motor degeneration until they die.

Skin Colour of Rabbits

  • Agouti: Full color, wild-type, dominant over all other colors.

  • Chinchilla: Lighter than agouti; dominant over Himalayan and albino.

  • Himalayan: White body with colored tips on ears, feet, tail, and snout; dominant over albino.

  • Albino: Pure white fur; recessive to all other types.

Combinations of Two Gene Pairs with Two Modes of Inheritance

  • Mendel's principle of independent assortment applies if the genes controlling each character are not located on the same chromosome (no genetic linkage).

Gene Interaction

  • Several genes influence a particular characteristic.

  • The cellular function of numerous gene products contributes to the development of a common phenotype.

  • Epigenesis: Each developmental step increases the complexity of an organ or feature and is controlled by many genes.

    • Example: Inner ear formation for detecting and interpreting sounds.

  • Epistasis: The expression of one gene pair masks or modifies the effect of another gene pair.

    • Examples: Grain color in corn, coat color in dogs.

    • The pigment anthocyanin is the product of a two-step biochemical pathway:

    • Starting molecule (colorless) --Enzyme 1 --> Intermediate (colorless) --Enzyme 2 --> Anthocyanin (purple)

  • Dog Coat Color Example:

    • ee: No dark pigment in fur (Yellow Lab)

    • eebb: Yellow fur, brown nose, lips, eye rims

    • E_bb: Chocolate Lab - Brown fur, nose, lips, eye rims

    • EB: Black Lab - Black fur, nose, lips, eye rims

    • eeB: Yellow fur, black nose, lips, eye rims

Multiple Genes or Polygenes

  • Two or more pairs of genes account for the phenotype.

  • Alleles do not exhibit dominance but have a quantitative effect.

  • Contributory/effective allele (C) vs. non-contributory/non-effective alleles (c).

  • Effects of contributory alleles are equal but cumulative (additive).

Examples of Polygenes

  • Anatomical: Height, weight, ear length in corn, degree of pigmentation in flower and skin.

  • Physiological: Metabolic traits, speed of running, milk production.

  • Behavioral: Mating calls, courtship rituals, ability to move to light.

  • Complex diseases: Diabetes, hypertension, arthritis, obesity.

X-Linkage in Drosophila

  • Observed by Thomas H. Morgan in 1910.

  • Difference in sex-chromosome composition of male and female Drosophila.

  • Hypothesis: Recessive allele for white eye is found on the X chromosome and absent in the Y chromosome.

  • Males cannot be homozygous or heterozygous for X-linked genes; they are called hemizygous.

X-Linked Genes

  • Genes described on the X chromosome.

  • X chromosomes exhibit patterns of inheritance different from autosomal genes.

  • Hemizygous: In males, as the Y chromosome lacks homology with the X chromosome.

  • SRY genes (sex-determining region Y) determine maleness.

Barr Bodies

  • Inactivated and highly condensed X chromosome attached to the nuclear membrane.

  • Which X chromosome is inactivated varies randomly from cell to cell.

  • If a woman is heterozygous for a sex-linked trait, some of her cells will express one allele, and some the other.

Sex-Linked Traits

  • Controlled by genes on sex chromosomes (X and Y); exhibit a pattern of inheritance related to sex.

  • X-linked recessive traits: Rare recessive allele located on the X chromosome; more common in males than females.

  • X-linked dominant traits: If the male is affected, he passes the condition to all his daughters but none to his sons.

  • Y-linked or Holandric traits: Occur in every son of an affected male; females are not affected since they do not have a Y chromosome.

Human X-Linked Traits:

  • Color blindness: Insensitivity to green or red light.

  • G-6-PD deficiency: Deficiency of glucose-6-phosphate dehydrogenase; severe anemic reaction following intake of primaquines in drugs and certain foods, including fava beans.

  • Hemophilia A: Classic form of clotting deficiency; deficiency of clotting factor VIII.

  • Hunter syndrome: Mucopolysaccharide storage disease resulting from iduronate sulfatase enzyme deficiency; short stature, claw-like fingers, coarse facial features, slow mental deterioration, and deafness.

  • Lesch–Nyhan Syndrome: Deficiency of hypoxanthine-guanine phosphoribosyltransferase enzyme (HPRT) leading to motor and mental retardation, self-mutilation, and early death.

  • Duchenne muscular dystrophy: Progressive, life-shortening disorder characterized by muscle degeneration and weakness; sometimes associated with mental retardation; deficiency of the protein dystrophin.

Sex-Limited Traits

  • Autosomal traits expressed exclusively in one sex.

  • Genes are found in both males and females, but expression is shown in only one sex with the suitable sex hormone.

Sex-Influenced Traits

  • Autosomal traits expressed in both sexes but more frequent in one sex than the other.