Mendel and the Gene Idea – Comprehensive Study Notes

Historical Background & Foundational Questions

• Charles Darwin (1859) acknowledged that the “laws governing heredity are for the most part unknown,” questioning why particular traits sometimes appear or skip generations.
• Two 19th-century hypotheses attempted to explain heredity:
  • Blending hypothesis: parental materials mix irreversibly (e.g., blue + yellow ⇒ green).
  • Particulate hypothesis: parents pass on discrete units of inheritance (genes) that retain identity across generations.
• Gregor Mendel used quantitative experiments with garden peas to validate the particulate view and establish modern genetics.

Mendel’s Experimental System

• Selected Pisum sativum because it offered:
  • Many readily distinguishable varieties/characters (flower color, seed shape, etc.).
  • \text{Short generation time} and production of large numbers of offspring.
  • Controlled mating: plants self-pollinate naturally; cross-pollination achievable by hand.
• Terminology:
  • Character = heritable feature (e.g., flower color).
  • Trait = variant of a character (purple vs. white flowers).
  • True-breeding line = produces offspring identical to parent for a given trait when self-pollinated.

Experimental Design & Generational Nomenclature

• Hybridization: cross two contrasting true-breeders.
  • P generation = parental true-breeding lines.
  • F₁ generation = first-filial hybrids.
  • F₂ generation = progeny from F₁ self- or cross-pollination.

Mendel’s Quantitative Observations

• Monohybrid cross (flower color):
  • F₁: all plants purple.
  • F₂: \approx 3:1 ratio purple :white (e.g., 705:224).
• Similar \approx 3:1 ratios obtained for six other characters (Table 14.1: seed color 6022:2001, seed shape 5474:1850, etc.).

Mendel’s Model (Law of Segregation)

1. Allelic variation: alternative versions of a gene (alleles) account for trait differences; each allele resides at a specific chromosomal locus.
2. Diploidy: an organism inherits two alleles per gene, one from each parent.
3. Dominance: if alleles differ, the dominant allele determines phenotype; the recessive allele is phenotypically silent in heterozygotes.
4. Segregation: the two alleles separate during gamete formation so a gamete carries only one allele (mirrors separation of homologous chromosomes in meiosis).

• Punnett-square representation (P = purple, p = white):
  \begin{array}{c|cc}
  & P & p\\hline
  P & PP & Pp\
  p & Pp & pp
  \end{array} ⇒ F₂ phenotypic ratio 3:1; genotypic ratio 1:2:1.

Genetic Vocabulary & Analytical Tools

• Homozygous (PP or pp) vs heterozygous (Pp).
• Phenotype (observable traits) vs genotype (genetic make-up).
• Testcross: cross an individual with dominant phenotype to a pp (homozygous recessive) tester; presence of any recessive offspring indicates heterozygosity.

Law of Independent Assortment

• Dihybrid cross (seed color Y/y & seed shape R/r):
  • P: YYRR × yyrr ⇒ F₁: YyRr.
  • F₂ progeny displayed ≈ 9:3:3:1 phenotypic ratio, supporting that allele pairs segregate independently during gametogenesis (applies to genes on different or very distant loci).

Probability Rules in Genetics

• Multiplication rule: probability of combined independent events = product of individual probabilities.
  • Example: probability of YYRR gamete pair =\frac14 \times \frac14 = \frac1{16}.
• Addition rule: probability of mutually exclusive events = sum of their probabilities.
  • Example: probability F₂ plant is heterozygous = P(Yy) + P(Rr) (calculated per gene).
• Complex crosses are treatable as simultaneous monohybrid crosses; probabilities for each gene are multiplied.

Beyond Simple Mendelian Patterns

Degrees of Dominance

• Complete dominance: heterozygote phenotype = dominant homozygote.
• Incomplete dominance: heterozygote intermediate (e.g., red CR CR × white CW CW ⇒ pink CR CW; F₂ ratio 1 : 2 : 1 for red:pink:white).
• Codominance: both alleles fully expressed in heterozygote (e.g., ABO blood type I^A I^B ⇒ AB phenotype).

Molecular Perspective on Dominance

• Alleles are DNA sequence variants; dominance often reflects level of gene product.
• Tay-Sachs disease illustrates three dominance levels:
  • Organismal: recessive.
  • Biochemical (enzyme activity): incomplete dominance.
  • Molecular (protein produced): codominance.

Frequency of Dominant vs Recessive Alleles

• Dominance ≠ commonality; polydactyly (extra digits) dominant yet rare.

Multiple Alleles

• ABO system governed by three alleles (I^A, I^B, i) producing four phenotypes (A, B, AB, O).

Pleiotropy

• Single gene influences multiple traits (e.g., sickle-cell allele affects RBC shape, organ function, malaria resistance).

Epistasis

• One gene masks/modifies expression of another.
  • Labrador coat color:
  • Pigment gene B/b (black vs brown)
  • Deposition gene E/e (color vs no color)
  • Dihybrid cross yields phenotypic ratio 9:3:4 (black:brown:yellow).

Polygenic (Quantitative) Inheritance

• Additive effects of 2⁺ genes; produces continuous variation.
  • Example: human skin color modeled by three genes A/a, B/b, C/c; distribution approximates a normal curve (genotypic class counts \frac{1}{64}, \frac{6}{64}, \dots).

Multifactorial Traits & Environmental Influence

• Phenotype = genotype + environment; e.g., nutrition impacts height, UV exposure influences skin tone.

Human Genetics & Mendelian Analysis

Limitations

• Long generation time, few offspring, ethical constraints limit controlled crosses; rely on pedigrees.

Pedigree Interpretation

• Symbols: squares ♂, circles ♀, filled = affected.
• Example traits:
  • Widow’s peak (dominant W_) vs straight hairline (ww).
  • Attached earlobes (recessive ff) vs free (F_).
• Probability calculations apply per child; each birth is an independent event.

Recessive Disorders

• Appear only in homozygotes; carriers are heterozygotes.
• Albinism: no melanin; genotype aa.
• Cystic fibrosis: defective \text{CFTR} chloride channel; 1/2500 Europeans affected.
• Sickle-cell disease: \beta-globin mutation; homozygotes suffer anemia, heterozygotes (trait) gain malaria resistance ⇒ example of balanced polymorphism.

Dominant Disorders

• Rare; may be lethal but persist when onset is post-reproductive.
• Achondroplasia: dwarfism (Dd).
• Huntington’s disease: neural degeneration beginning ≈ 35{-}40 yrs; dominant allele with late onset.

Multifactorial Disorders

• Heart disease, diabetes, cancer, alcoholism, mental illness result from polygenic inheritance + environment; lifestyle choices modify risk.

Genetic Testing & Counseling

• Counselors apply Mendelian probability to advise families.
• Carrier testing: DNA or biochemical assays identify heterozygotes.
• Fetal testing:
  • Amniocentesis: withdraw amniotic fluid; karyotype after \text{several weeks}.
  • Chorionic Villus Sampling (CVS): biopsy placenta; faster (hours) but slightly higher risk.
  • Imaging: ultrasound, fetoscopy.
• Newborn screening: routine heel-prick tests (e.g., PKU) allow early intervention.
• Ethical considerations: informed consent, privacy, discrimination, reproductive choices.

Synthesis: The Mendelian Framework

• Segregation and independent assortment remain cornerstones for all genetic patterns, even complex ones.
• Phenotype reflects cumulative genotype and environment; modern genetics integrates molecular biology, population genetics, and ethical responsibility.