Genetics: Codominance and Sickle Cell Anemia

Mendelian Genetics

• Mendel determined that discrete units of inheritance exist and predicted their behavior in the formation of gametes.
• His postulates became the basis of Transmission Genetics.

Factors that Contributed to Mendel's Success

• Good choice of experimental organism: garden peas are easy to grow and need only one season to mature.
• Use of true-breeding (homozygous) plants.
• Choice of varieties that differed in only one trait (monohybrid cross).
• Accurate record-keeping and good background in statistics.

Definitions of Terms

• Gene: the physical and functional unit that helps determine the traits passed on from parents to offspring; a nucleotide sequence in DNA that specifies a polypeptide or RNA.
• Locus: the position on a chromosome where a gene is located.
• Allele: any two or more related genes of a trait.
  • Dominant: expresses its effect over another allele; masks the recessive allele in a heterozygous organism.
  • Recessive: masked in a heterozygous individual by the presence of a dominant allele.
• Phenotype: the visible appearance of an organism.
• Genotype: the genetic constitution of an organism.

Mendelian Laws

• Law of Segregation: an organism possesses two alleles encoding a trait and these two alleles separate in equal proportions during gamete formation.
• Law of Independent Assortment: alleles from one locus segregate into gametes independently of those from another locus.

Law of Segregation

• Applies to monohybrid crosses, where two individuals are crossed involving one character.
• Each gamete contains only one factor (allele) from each pair.
• Fertilization gives the offspring two factors for each trait.
• Example: YY (homozygous yellow) x yy (homozygous green) results in Yy (heterozygous) offspring.

Law of Independent Assortment

• Applies to dihybrid crosses, where two individuals are crossed involving two characters.
• Genes encoding different characters assort independently when gametes are formed.
• Based on the random separation of homologous pairs of chromosomes in Anaphase I of Meiosis.

Punnett Square

• A table listing all possible genotypes resulting from a cross.
• Used to determine the probability of offspring genotypes and phenotypes.
• How to make a Punnett Square:
  1. Choose letters to represent the trait.
  2. Draw the Punnett square.
  3. Put the female parent on the left and the male parent at the top.
  4. Segregate alleles into gametes.
  5. Perform the cross: bring letters (alleles) "down" and "across".

Test Crosses

• A cross between an individual with a dominant trait and an individual with a recessive trait to determine the genotype of the dominant parent.
• Monohybrid test cross: used to determine the genotype of a parent exhibiting a dominant trait.
• Dihybrid test cross: used to determine the genotype of a parent exhibiting a dominant trait for two characters.

Forked-Line Method or Branch Diagram

• A method used to determine the gametes formed by an individual with multiple heterozygous characters.
• The number of gamete types formed by an individual is determined by the formula 2^n, where n is the number of heterozygous characters.

Multihybrid Cross

• A cross involving more than two characters.
• Can be solved by making separate monohybrid crosses for each character and computing probabilities from the results.Here are the study notes for the text:

Non-Mendelian Genetics

• Complete Dominance: In autosomal inheritance, a dominant allele is always expressed, while a recessive allele is only expressed when homozygous recessive.
  • Examples: Huntington's disease, achondroplasia (short-limbed dwarfism), polycystic kidney disease, polydactyly
• Autosomal Recessive Inheritance: It takes two copies of the gene for the trait to be expressed.
  • Examples: Cystic fibrosis, Tay-Sachs, Hemochromatosis, phenylketonuria (PKU), deafness/hearing loss

Incomplete or Partial Dominance

• Incomplete Dominance: A dominant allele cannot completely mask the effect of a recessive allele, resulting in a blended phenotype.
• Example: Red-flowered parent crossed with a white-flowered parent produces pink-flowered offspring (Rr).

Co-dominance

• Co-dominance: Both alleles involved are equally dominant, and the phenotypes of both parent alleles are simultaneously expressed in the offspring.
• Examples: MN blood group, sickle cell anemia, and hemoglobin in humans

Multiple Allelism

• Multiple Allelism: A series of three or more alternative forms of a gene, where only two can exist in a normal, diploid individual.
• Example: ABO blood group, with three alleles (A, B, and O) that result in four blood types (A, B, AB, and O)

Lethal Alleles

• Lethal Alleles: Alleles that cause an organism to die when present in a homozygous condition.
• Types of Lethal Alleles:
  • Recessive Lethal Genes: Homozygous recessive individuals die.
  • Dominant Lethal Genes: Heterozygous individuals die.
  • Conditional Lethal Genes: Lethal alleles that exert their effects only under certain environmental conditions.
  • Semi-lethal Genes: Genes that kill some individuals in a population, but not all of them.

Modifier Genes

• Modifier Genes: Genes that modify the expression of a second gene.
• Example: Gene D (controls color intensity) modifies the expression of gene B (controls coat color) in mice.

Gene Interactions

• Inter-allelic Genetic Interaction: Independent genes interact with one another to produce a single phenotypic trait.
• Non-Epistatic Inter-allelic Genetic Interaction: Each gene pair affects the same character, and there is complete dominance at both gene pairs.
• Epistasis: One gene masks or modifies the effect of another gene pair, altering the phenotype.
• Recessive Epistasis: A recessive allele of one gene masks the effects of either allele of the second gene.
• Example: Fur color in Labrador Retrievers, controlled by gene E (melanin production) and gene B (melanin deposition).### Gene Interactions
• Dominant Epistasis: a dominant allele of one gene masks the action of either allele of another gene.
  • Example 1: Solid fruit color in summer squash
    • Individuals with at least one W allele have white fruit, those with at least one Y allele have yellow fruit, and those with both recessive alleles have green fruit.
    • W also inhibits the production of yellow pigment.
  • Example 2: Color of flowers in foxglove
    • The dominant W gene controls flower color by allowing pigment deposition only at the throat region.
    • Colored petals are produced when the dominant W gene is absent or non-functional.
    • Gene D codes for an enzyme that can convert a colorless precursor to dark red pigment.
    • Recessive d codes for an enzyme that can form a light red pigment from the colorless precursor.

Types of Epistasis

• Dominant Suppression: a dominant allele of one gene completely suppresses the phenotypic expression of alleles of another gene.
  • Example: Feather color in chickens
    • The dominant allele C is required for feather color, and the recessive allele c results in white feathers.
    • The dominant suppressor allele I can suppress the color-producing action of the C allele.
• Complementary Epistasis: both gene loci have homozygous recessive alleles and produce identical phenotypes.
  • Example: Flower color in sweet pea
    • The recessive alleles cc and pp produce white flowers.
    • The dominant alleles C and P produce colored flowers.
• Duplicate Dominant Epistasis: dominant alleles of both gene loci produce the same phenotype without cumulative effect.
  • Example: Flower color in bean
    • The dominant alleles produce the same phenotype, and only one copy of either dominant allele is required for the dominant phenotype.

Pleiotropism

• Definition: the phenomenon of multiple effects of a single gene.
• Examples:
  • The gene for phenylketonuria (PKU) produces various phenotypic traits, including short stature, mental deficiency, and physical characteristics.
  • Marfan syndrome: a human malady resulting from an autosomal dominant mutation in the gene encoding the connective tissue protein fibrillin.
  • Sickle cell anemia: a mutation of a beta-globin gene that can cause various organ problems.

Environmental Influence on Gene Expression

• Examples:
  • Coat color distribution in Himalayan rabbits and Siamese cats in response to temperature.
  • Temperature-dependent sex determination in freshwater turtle Emys orbicularis embryos.
  • Anthocyanin production in maize in response to temperature.
  • Chemicals ingested or drugs taken by pregnant women can cause birth deformities.
  • Deficiency in folic acid in pregnant women can cause birth abnormalities like spina bifida.
  • Internal environment: hormones, such as testosterone and dihydrotestosterone, influence gene expression.

Penetrance and Expressivity

• Penetrance: the extent to which a gene or set of genes is expressed in the phenotypes of individuals carrying it.
  • Complete Penetrance: genes that always produce a complete phenotypic expression.
    • Examples: pea flowers, guinea pig coat color.
  • Incomplete Penetrance: genes that do not always produce a complete phenotypic expression.
    • Examples: polydactyly, retinoblastoma, diabetes mellitus.
• Expressivity: the degree of effect produced by a penetrant genotype.
  • Examples: polydactyly, retinoblastoma.

Twinning: Concordance and Discordance

• Identical twins: derived from one zygote that splits during development.
• Fraternal twins: come from two different eggs fertilized separately at the same time.
• Concordance: the probability that a pair of individuals will both have a certain characteristic, given that one of the pair has the characteristic.
• Discordance: the degree of dissimilarity in a pair of twins with respect to the presence or absence of a disease or trait.
• Examples: monozygotic twins with Beckwith-Wiedemann syndrome and Russell-Silver syndrome, discordance in metabolism.