Beyond Dominant and Recessive Principles

Exceptions to Mendelian Principles and Complex Inheritance Patterns

• Mendel’s Simplified System: Gregor Mendel worked with garden peas, which are genetically simple because:     * Most traits are controlled by a single gene.     * Each gene has only two alleles.     * One allele is completely dominant over the other.

• The Genotype-Phenotype Relationship: In nature, this relationship is rarely as simple as the one Mendel observed. Exceptions and complexities include:     * Incomplete dominance.     * Multiple alleles.     * Co-dominance.     * Pleiotropy.     * Epistasis.     * Polygenic inheritance.     * X-linked (sex-linked) inheritance.

• Key Concepts in Modern Genetics:     * Genes are carried on chromosomes.     * Prokaryotes (bacteria) can exchange genetic material.     * Not all inheritance follows Mendelian Laws.

Incomplete Dominance and Allelic Blending

• Definition: Incomplete dominance occurs when one allele for a gene is not completely dominant over another.

• Phenotypic Outcome: The heterozygous phenotype expresses an intermediate, blended state somewhere between the two homozygous phenotypes.

• Flower Color Example (Snapdragons/Peas):     * Genotypes:         * $RR$: Red flowers.         * $rr$: White flowers.         * $Rr$: Pink flowers.     * Mechanism: The $Rr$ heterozygote makes $50\%$ less color than the $RR$ homozygote.

• Generational Cross Results:     * $P$ Generation: True-breeding red ($RR$) $X$ True-breeding white ($rr$).     * $F_{1}$ Generation (Hybrids): $100\%$ pink flowers ($Rr$).     * $F_{2}$ Generation (Self-pollination of $F_{1}$): Reverts to a ratio of $1:2:1$.         * $25\%$ Red ($RR$).         * $50\%$ Pink ($Rr$).         * $25\%$ White ($rr$).     * Comparison: This is statistically similar to flipping two pennies.

Multiple Alleles and Human Blood Types

• Definition: A given gene may have more than two possible alleles within a population. While a population has multiple alleles, an individual organism still only carries two.

• Impact: Multiple alleles increase the possible phenotypic variations and can establish a hierarchy of dominance.

• Human ABO Blood Groups:     * Controlled by three alleles: $I^{A}$, $I^{B}$, and $i$.     * Type A: Genotypes $I^{A}I^{A}$ or $I^{A}i$ (also written as $AA$ or $AO$). Produces Type A antigens and anti-B antibodies.     * Type B: Genotypes $I^{B}I^{B}$ or $I^{B}i$ (also written as $BB$ or $BO$). Produces Type B antigens and anti-A antibodies.     * Type AB: Genotype $I^{A}I^{B}$ ($AB$). Produces both Type A and Type B antigens. Known as the Universal Recipient because they have no anti-A or anti-B antibodies.     * Type O: Genotype $ii$ ($OO$). Produces no antigens and both anti-A and anti-B antibodies. Rejects blood from Types A, B, and AB.

• Rabbit Coat Color Example:     * One gene controlled by four alleles: $C$, $c^{ch}$, $c^{h}$, and $c$.     * $C$ is dominant to all other alleles.     * $c$ is recessive to all other alleles.

Co-Dominance

• Definition: Two alleles affect the phenotype equally and separately. Unlike incomplete dominance, the phenotype is not a blend; both traits show up simultaneously.

• Examples:     * ABO Blood Groups: The $I^{A}$ and $I^{B}$ alleles are co-dominant. Heterozygotes ($I^{A}I^{B}$) produce both glycoprotein antigens on the Red Blood Cell (RBC) surface.     * Chicken Feathers: Certain breeds show both black and white feathers rather than gray.     * Cattle Hide Color: "Roan" cattle hide, where red and white hairs are mixed.

Pleiotropy

• Definition: A single gene affects more than one phenotypic characteristic (one gene, many traits).

• Examples:     * Achondroplasia (Dwarfism): A dominant inheritance pattern where a single gene mutation affects bone growth and overall stature.         * Genotype counts: $AA$ is lethal; $Aa$ results in dwarfism; $aa$ results in "normal" height.         * In an $Aa imes Aa$ cross, the live offspring ratio is $2:1$ ($67\%$ dwarf, $33\%$ normal).     * Acromegaly (Gigantism): Exemplified by André the Giant.     * Sickle Cell Anemia: A single mutation affects blood cell shape, which leads to a cascade of effects including anemia, physical weakness, and damage to the brain, spleen, and heart.

• Historic Note: This is also observed in the domestication of silver foxes (The Foxes example).

Epistasis

• Definition: One gene completely masks the expression of another gene at a different locus.

• Mouse and Labrador Retriever Coat Color:     * Determined by two separate genes.     * Gene 1 ($C, c$ or $E, e$): Determines if pigment will be deposited. $C$ or $E$ (dominant) = pigment; $cc$ or $ee$ (recessive) = no pigment (albino or yellow).     * Gene 2 ($B, b$): Determines the color of the pigment. $B$ (dominant) = Black; $b$ (recessive) = Brown/Chocolate.     * Mechanism: If the organism is $cc$ or $ee$, it will be albino/yellow regardless of whether the $B$ allele is dominant or recessive.     * Modified Mendelian Ratios: The typical $9:3:3:1$ dihybrid ratio becomes $9:3:4$.     * Labrador Retriever Phenotypes:         * Black: B_E_         * Chocolate/Brown: bbE_         * Yellow: __ee

Polygenic Inheritance and Continuous Variation

• Definition: Phenotypes are determined by the additive effects of two or more genes on a single character.

• Continuous Variation: Unlike discontinuous variation (e.g., blood type, where you are either A, B, AB, or O), polygenic traits exist on a continuum.

• Graphical Representation: These traits usually result in a bell-shaped curve (normal distribution) where most individuals are near the average and few are at the extremes.

• Example Traits:     * Human skin color (controlled by at least 4 different genes).     * Height and weight.     * Intelligence and musical talent.     * Mathematical aptitude.     * Susceptibility to certain cancers or illnesses.     * Kernel color in corn.     * Eye color in fruit flies.

• Skin Color and Albinism: While skin color is polygenic (melanin production), Albinism can be inherited as a single gene trait where $aa$ prevents the enzyme tyrosine from converting into melanin.

The Chromosomal Basis of Sex and Sex-Linked Traits

• Discovery: Identified by T.H. Morgan at Columbia University in $1910$ using Drosophila melanogaster (fruit flies).

• Drosophila as a Model Organism:     * Prolific breeders with $2$-week generation times.     * Possess only $4$ pairs of chromosomes ($XX$ = female, $XY$ = male).

• Human Chromosomes:     * $23$ pairs total.     * Pairs $1$ through $22$ are Autosomes (homologous, non-sex determining).     * The $23^{rd}$ pair consists of Sex Chromosomes.         * Females ($XX$): Homologous pair; provides gene redundancy.         * Males ($XY$): Non-homologous; no gene redundancy for X-linked traits.

• The Y Chromosome:     * Contains fewer than $30$ genes.     * SRY Gene: The "Sex-determining Region Y." It is the master regulator for maleness, turning on genes for male hormone production (an example of pleiotropy).

• The X Chromosome:     * Carries many genes unrelated to sex determination.     * Over $60$ diseases are traced to the X chromosome.     * X-Linked Dominant/Recessive Patterns: In Morgan’s fly experiment, white eyes (recessive) appeared only in males in the $F_{2}$ generation because males only need one copy of the recessive allele to express the trait.

X-Inactivation and Mosaicism

• Barr Bodies: In female mammals, one of the two X chromosomes in every cell is inactivated during embryonic development and condenses into a compact object called a Barr Body.

• Genetic Mosaicism: The selection of which X chromosome becomes the Barr Body is random. This lead to "patchwork" traits.

• Tortoiseshell Cats: This phenotype (patches of black and orange) can only occur in females because the color gene is on the X chromosome, and different patches of skin have different X chromosomes inactivated.

Environmental Influences on Phenotype

• Nature vs. Nurture: Phenotype is controlled by both genes and the environment.

• Specific Examples:     * Hydrangea flowers: Color is determined by soil pH.     * Arctic Fox: Coat color is influenced by heat-sensitive alleles (white in winter, dark in summer).     * Himalayan Rabbits: Warm body parts grow white fur, while cool body parts (ears, nose, paws) grow black fur.     * Drosophila melanogaster: Straight wings occur if raised at $16^{\circ}C$; curly wings occur at $25^{\circ}C$.

• Temperature-Dependent Sex Determination (TSD) in Reptiles:     * Turtles/Tortoises: Males at cool temperatures, females at warm temperatures.     * Lizards/Alligators: Males at warm temperatures, females at cool temperatures.     * Crocodiles/Snapping Turtles: Females at both extreme temperatures (cool and warm), males at intermediate temperatures.

Teratogens

• Definition: Environmental factors that permanently alter traits or cause birth defects.

• Examples:     * Antibiotics and Drugs: Barbiturates (phenobarbital), Tranquilizers (reserpine), Sulphonamides.     * Specific Substances: Alcohol, Accutane (anti-acne), Thalidomide (anti-nausea), Diethylstilbestrol (DES - synthetic hormone).     * Other Factors: Radiation, Viruses (e.g., Measles), Industrial chemicals (arsenic, mercury).

Non-Mendelian Organelle Inheritance and Bacterial Exchange

• Cytoplasmic Inheritance:     * Mitochondria and plastids (like chloroplasts) contain their own small genomes.     * These are inherited only from the mother (maternal inheritance) because the egg provides the cytoplasm and organelles to the zygote.

• Prokaryotic Genetic Material Exchange:     * Bacterial Conjugation: Bacteria exchange genes via a sex pilus that initiates contact, followed by the formation of a conjugation tube (cytoplasmic bridge).     * Plasmids: Small circular DNA molecules that replicate independently of the main chromosome. They often carry genes for antibiotic resistance, metabolic tasks, or conjugation.

Summary of Genetic Disorders to Know

• Autosomal Recessive: Cystic Fibrosis, Phenylketonuria (PKU), Tay Sachs, Sickle Cell Anemia.

• Autosomal Dominant: Achondroplasia, Huntington’s Disease (noted for late onset).

• Sex-Linked Recessive: Hemophilia, Red-green colorblindness, Duchenne Muscular Dystrophy, Nystagmus.

• Chromosomal: Turner’s Syndrome ($X0$), Klinefelter’s ($XXY$), Trisomy $21$ (Down Syndrome).

• Note on Abundance: Dominant alleles are not necessarily more common in a population. For example, polydactyly is a dominant trait but only occurs in $1$ in $400$ births.

Questions & Discussion

• Question 1: Three babies were mixed up. Couple I (A, A), Couple II (A, B), Couple III (B, O). Baby 1 (B), Baby 2 (O), Baby 3 (AB). Find the match.     * Answer Logic: Couple III (B/O) must have baby 1 (B) or 2 (O). Couple II (A/B) consists of the only parents capable of having baby 3 (AB). Couple I (A/A) can have baby 2 (O) if both are heterozygous. Correct combination: I-2, II-3, III-1.

• Question 2: A mother (Type B) has two children (Type A and Type O). Her husband is Type O.     * Conclusion: The Type O husband ($ii$) could father the Type O child ($Bi imes ii = ii$), but he cannot father a Type A child unless the mother has an $A$ allele, which she doesn't. Thus, the husband could be the father of the Type O child but not the Type A child.

• Question 3: Sex-linked recessive vermilion eyes in flies. Female (vermilion) $X$ Wild-type male ($X^{+}Y$). What percentage of F1 males have vermilion eyes?     * Answer: $100\%$. All males inherit their X from their mother.

• Question 4: Barring in chickens (Sex-linked dominant $B$). To have all chicks of one sex barred at hatching, what cross is needed?     * Selection: Nonbarred males $X$ barred females.

• Question 5: Mother is carrier for color blindness (normal vision, father was color-blind). Marries color-blind male. Probability their son is color-blind?     * Answer: $1/2$ (or $50\%$). The son has a $50\%$ chance of inheriting the $X^{c}$ from his carrier mother.

• Question 6: Achondroplastic dwarf man (normal vision) marries color-blind woman (normal height). Dwarfism is autosomal dominant ($D$); color blindness is X-linked recessive ($r$).     * Female children expected to be color-blind dwarfs: None. The father has normal vision ($X^{R}Y$), so all daughters will receive a dominant $X^{R}$ allele.     * Male children expected to be color-blind and normal height: Half ($50\%$). All sons get $X^{r}$ from the mother. The father is heteroyzgous for dwarfism ($Dd$), so half the sons get $d$ (normal height).