Principles of Inheritance and Variation Comprehensive Study Notes

Fundamental Concepts in Genetics

• Genetics: The exhaustive study of inheritance, heredity, and the variation of characters. It encompasses the study of genes and chromosomes.
• Inheritance: The process of transmission of characters from parents to offspring (progeny). It constitutes the fundamental basis of heredity.
• Variation: The degree of difference observed between parents and their offspring.
• Character: A heritable feature observed among parents and offspring, such as eye colour.
• Trait: The specific variants of a character. For example, brown eyes, blue eyes, emerald eyes, or grey eyes are traits of the character eye colour.
• Alleles (Allelomorphs): Alternative forms of a gene. For example, $T$ (tall) and $t$ (dwarf) represent two alleles of a gene governing the character of height.
• Homozygous: A condition where a chromosome pair carries identical alleles of a gene (e.g., $TT$, $tt$, $YY$, $yy$). This is also referred to as a pure line or true breeding.
• Heterozygous: A condition where a chromosome pair carries dissimilar alleles of a gene (e.g., $Tt$, $Yy$, $Bb$).
• Dominant Character: A character expressed in the heterozygous condition, typically indicated by a capital letter. Examples include Widow's Peak, Cleft Chin, Dimples, Brown/Black Hair, Freckles, and Brown Eyes.
• Recessive Character: A character suppressed in the heterozygous condition, typically indicated by a small letter. Examples include No Widow's Peak, No Cleft Chin, No Dimples, Blonde Hair, No Freckles, and Gray/Blue Eyes.
• Phenotype: The physical expression or observable appearance of a character.
• Genotype: The genetic constitution or internal coding of a character.
• Hybrid: An individual produced by the mating of genetically unlike parents.

Gregor Mendel and His Laws of Inheritance

• Gregor Mendel: Known as the Father of Genetics. He conducted hybridization experiments on garden peas (Pisum sativum) for a period of $7$ years, from $1856$ to $1863$.
• Steps in Making a Cross in Pea Plants:
  1. Selection: Choosing two pea plants with contrasting characters.
  2. Emasculation: The removal of anthers from one plant (the female parent) to prevent self-pollination.
  3. Pollination: Collecting pollen grains from the male parent and transferring them to the stigma of the female parent.
  4. Collection and Germination: Gathering the resulting seeds and germinating them to produce offspring.
• Seven True Breeding Varieties Selected by Mendel:
  1. Stem Height: Tall (Dominant) vs. Dwarf (Recessive).
  2. Flower Position: Axial (Dominant) vs. Terminal (Recessive).
  3. Flower Colour: Violet (Dominant) vs. White (Recessive).
  4. Pod Shape: Inflated/Full (Dominant) vs. Constricted (Recessive).
  5. Pod Colour: Green (Dominant) vs. Yellow (Recessive).
  6. Seed Shape: Round (Dominant) vs. Wrinkled (Recessive).
  7. Seed Colour: Yellow (Dominant) vs. Green (Recessive).

Inheritance of One Gene (Monohybrid Cross)

• Definition: A cross involving two plants that differ in only one character pair.
• Mendel's Observation: Crossing a homozygous tall ($TT$) with a homozygous dwarf ($tt$) produces a first filial ($F_1$) generation of heterozygous tall ($Tt$) plants.
• Selfing of $F_1$: Self-pollinating $Tt \times Tt$ results in the second filial ($F_2$) generation.
• $F_2$ Results:
  • Punnett Square (Checker Board): A tool used to calculate the probability of genotypes.
  • Monohybrid Phenotypic Ratio: $3 \text{ Tall} : 1 \text{ Dwarf}$, or $3:1$.
  • Monohybrid Genotypic Ratio: $1 \text{ Homozygous tall (TT)} : 2 \text{ Heterozygous tall (Tt)} : 1 \text{ Homozygous dwarf (tt)}$, or $1:2:1$.
• Mathematical Representation: The proportions can be expressed using a binomial expression $(ax + by)^2$. For a cross of $Tt$, it is $(\frac{1}{2} T + \frac{1}{2} t)^2$.
  • $(\frac{1}{2} T + \frac{1}{2} t) \times (\frac{1}{2} T + \frac{1}{2} t) = \frac{1}{4} TT + \frac{1}{2} Tt + \frac{1}{4} tt$.
• F3 and F4 Generations: Mendel found that dwarf $F_2$ plants continued to produce only dwarf plants, confirming their genotype as homozygous recessive ($tt$).

Back Cross and Test Cross

• Backcross: A cross between a hybrid and any of its parents.
• Testcross: The crossing of an organism exhibiting a dominant phenotype with a recessive individual to determine the unknown genotype.
  • If all offspring show the dominant phenotype, the unknown is homozygous dominant.
  • If offspring are $50$% dominant and $50$% recessive, the unknown is heterozygous.
  • Monohybrid Test Cross Ratio: $1:1$.

Mendel's Laws of Inheritance (Laws 1 and 2)

• First Law: Law of Dominance:
  • Characters are controlled by discrete units called factors (now known as genes).
  • Factors occur in pairs.
  • In a dissimilar pair of factors, one member dominates (dominant) over the other (recessive).
• Second Law: Law of Segregation:
  • During gamete formation, the factors (alleles) of a character pair segregate from each other so that a gamete receives only one of the two factors.
  • Homozygous parents produce similar gametes; heterozygous parents produce two kinds of gametes in equal proportion.

Inheritance of Two Genes (Dihybrid Cross)

• Definition: A cross between two parents differing in two pairs of contrasting characters (e.g., Round Yellow $RRYY$ vs. Wrinkled Green $rryy$).
• $F_1$ Generation: All offspring are heterozygous Round Yellow ($RrYy$).
• $F_2$ Generation:
  • Dihybrid Phenotypic Ratio: $9 \text{ Round Yellow} : 3 \text{ Round Green} : 3 \text{ Wrinkled Yellow} : 1 \text{ Wrinkled Green}$, or $9:3:3:1$.
  • Mathematical Derivation: This ratio is a combination series of $(3 \text{ Yellow} : 1 \text{ Green}) \times (3 \text{ Round} : 1 \text{ Wrinkled})$, which is $(3:1) \times (3:1) = 9:3:3:1$.
  • Dihybrid Genotypic Ratio: $1:2:1:2:4:2:1:2:1$. Breakdown includes: $RRYY=1, RRYy=2, RrYY=2, RrYy=4, RRyy=1, Rryy=2, rrYY=1, rrYy=2, rryy=1$.
• Third Law: Law of Independent Assortment: When more than one pair of characters are involved in a cross, the factor pairs segregate independently of each other.

The Concept of Dominance

• Every gene contains information for a specific trait. In a heterozygote, there are two types of alleles:
  1. Unmodified Allele: The normal or functioning allele, generally dominant, representing the original phenotype.
  2. Modified Allele: Generally recessive due to changes in the gene.
• Scenarios for Modified Alleles:
  • Case 1: Produces a normal or less efficient enzyme; phenotype remains same (equivalent to unmodified).
  • Case 2: Produces a non-functional enzyme; phenotype depends on the unmodified allele (modified becomes recessive).
  • Case 3: Produces no enzyme at all; phenotype depends on the unmodified allele (modified becomes recessive).

Non-Mendelian Inheritance

• Incomplete Dominance: Inheritance where the offspring shows an intermediate character between parents.
  • Examplars: Flower colour in Snapdragon (Antirrhinum sp.) and Four-O'Clock Plant (Mirabilis jalapa).
  • Results: Red ($RR$) $\times$ White ($rr$) yields Pink ($Rr$). The $F_2$ phenotypic and genotypic ratios are identical: $1 \text{ Red} : 2 \text{ Pink} : 1 \text{ White}$ ($1:2:1$).
• Co-dominance: Inheritance where both alleles of a gene are expressed in a hybrid.
  • Example: ABO blood grouping in humans, controlled by gene $I$.
  • Alleles: $I^A$, $I^B$, and $i$. $I^A$ and $I^B$ produce different sugar polymers (antigens); $i$ produces none.
  • Genotypes and Blood Types:
    • $I^A I^A$ or $I^A i$: Type A.
    • $I^B I^B$ or $I^B i$: Type B.
    • $I^A I^B$: Type AB (Both express their own sugars).
    • $ii$: Type O.
• Multiple Allelism: The presence of more than two alleles governing the same character in a population (e.g., $I^A$, $I^B$, and $i$ for ABO groups).
• Polygenic Inheritance: Traits controlled by several genes where the effect of each allele is additive and influenced by the environment.
  • Example: Human skin colour, assumed to be controlled by three genes ($A, B, C$).
  • Darkest: $AABBCC$; Lightest: $aabbcc$; Intermediate: $AaBbCc$.
• Pleiotropy: A single gene exhibiting multiple phenotypic expressions.
  • Example: Phenylketonuria (PKU) causes mental retardation and reduced hair/skin pigmentation.
  • Example: Starch synthesis in pea plants. $BB$ produces large starch grains; $bb$ produces small grains; $Bb$ produces intermediate size (showing incomplete dominance).

Chromosomal Theory of Inheritance

• Mendel's Lack of Initial Recognition: Due to difficult communication, his new mathematical approach, the inability to explain continuous variation, and lack of physical proof for "factors."
• Rediscovery (1900): Independently rediscovered by Hugo de Vries, Carl Correns, and Erich von Tschermak.
• The Theory (1902): Proposed by Walter Sutton and Theodore Boveri. They established that the pairing and separation of chromosomes lead to the segregation of factors they carry.
• Key Statements:
  • Chromosomes are the vehicles of heredity.
  • Identical chromosomes form homologous pairs.
  • Homologous pairs segregate during gamete formation.
  • Independent chromosome pairs segregate independently.
  • Genes are located on chromosomes.

Linkage and Recombination

• Thomas Hunt Morgan: Proved the chromosomal theory using Drosophila melanogaster (fruit flies).
• Drosophila as a Model Organism:
  • Grows on simple synthetic medium.
  • Short life cycle ($12-14$ days).
  • Breeds year-round with hundreds of progeny per mating.
  • Clear sexual dimorphism (males are smaller).
  • Variations visible under low-power microscopes.
• Linkage: Physical association of two or more genes on a chromosome. Linked genes do not show independent assortment.
• Recombination: Generation of non-parental gene combinations due to crossing over or independent assortment.
• Morgan's Findings:
  • Tightly linked genes (e.g., yellow body and white eye) show low recombination ($1.3$%).
  • Loosely linked genes (e.g., white eye and miniature wing) show high recombination ($37.2$%).
• Genetic Mapping: Alfred Sturtevant used recombination frequency to measure distances and map gene positions on chromosomes. This became the basis for projects like the Human Genome Project.

Sex Determination Mechanisms

• Allosomes (Sex Chromosomes): Chromosomes involved in determining sex (e.g., $X$ and $Y$).
• Autosomes: All chromosomes other than sex chromosomes; their number is identical in males and females.
• Mechanisms:
  • XX-XO: Male is heterogametic ($XO$), female is homogametic ($XX$). Observed in insects like grasshoppers.
  • XX-XY: Male is heterogametic ($XY$), female is homogametic ($XX$). Observed in humans and Drosophila.
  • ZZ-ZW: Female is heterogametic ($ZW$), male is homogametic ($ZZ$). Observed in birds.
• Sex Determination in Humans: Humans have $23$ pairs of chromosomes ($22$ pairs of autosomes + $1$ pair of sex chromosomes). The sperm (carrying either $X$ or $Y$) determines the sex of the offspring.
• Sex Determination in Honeybees (Haplodiploid System):
  • Fertilized eggs develop into females (Queen or Worker, $32$ chromosomes, diploid).
  • Unfertilized eggs develop into males (Drone, $16$ chromosomes, haploid) via parthenogenesis.
  • Males produce sperm by mitosis and have no father or sons, only grandfathers and grandsons.

Mutation and Pedigree Analysis

• Mutation: A sudden heritable change in DNA sequences resulting in genotype and phenotype changes.
  • Point Mutation: Change in a single base pair of DNA (e.g., Sickle cell anaemia).
  • Frame Shift Mutation: Insertion or deletion of base pairs shifting the reading frame.
  • Mutagens: Agents inducing mutation. Physical (UV radiation, X-rays, $\alpha$, $\beta$, $\gamma$ rays) and Chemical (Mustard gas, phenol, formalin).
• Pedigree Analysis: Study of family history to trace genetic traits, abnormalities, or diseases over generations.
  • Symbols: Squares (Male), Circles (Female), Diamond (Sex unspecified), Shaded (Affected), Horizontal line (Mating), Double line (Consanguineous mating).

Genetic Disorders

• Mendelian Disorders: Caused by mutation in a single gene.
  • Haemophilia (Royal Disease): X-linked recessive. Affects blood clotting protein. Queen Victoria was a carrier.
  • Colour Blindness: X-linked recessive; defect in red or green cones. Occurs in $8$% of males and $0.4$% of females.
  • Sickle Cell Anaemia: Autosomal recessive. Substitution of Glutamic acid ($Glu$) by Valine ($Val$) at the $6^{th}$ position of the $\beta$-globin chain ($GAG$ to $GUG$ substitution).
  • Phenylketonuria (PKU): Inborn error of metabolism; autosomal recessive. Lack of phenylalanine hydroxylase leads to phenylalanine accumulation, causing mental retardation.
  • Thalassemia: Autosomal recessive blood disease involving reduced synthesis of globin chains.
    • $\alpha$-Thalassemia: Genes $HBA1$ and $HBA2$ on chromosome $16$ are affected.
    • $\beta$-Thalassemia: Gene $HBB$ on chromosome $11$ is affected.
• Chromosomal Disorders: Caused by absence, excess, or abnormal arrangement of chromosomes.
  • Aneuploidy: Loss or gain of chromosomes (Nullisomy $2n-2$, Monosomy $2n-1$, Trisomy $2n+1$, Tetrasomy $2n+2$).
  • Polyploidy: Increase in whole sets of chromosomes (common in plants).
  • Down's Syndrome: Trisomy of chromosome $21$ ($47$ chromosomes). Features: Short stature, round head, furrowed tongue, simian crease on broad palm, retarded development.
  • Klinefelter's Syndrome: Additional X-chromosome in males ($44A + XXY$). Features: Masculine development with feminine traits like Gynaecomastia (breast development), sterile.
  • Turner's Syndrome: Absence of one X-chromosome in females ($44A + X0$, $45$ chromosomes). Features: Sterile, rudimentary ovaries, dwarfism, lack of secondary sexual characters.