K

Lecture 1: Mendelian Genetics and Monogenic Inheritance – Vocabulary Flashcards

Mendel's Principles and Monogenic Inheritance

  • Genes exist as alternate forms (alleles) and control inherited traits. Each individual carries two alleles per gene.

  • Law of Segregation: during gamete formation, paired alleles segregate so each gamete gets one allele.

  • Law of Independent Assortment: alleles of different genes assort independently in the formation of gametes (apply to unlinked genes).

  • Genotype = allelic composition; Phenotype = outward trait; Homozygous = same alleles; Heterozygous = different alleles.

  • Dominant allele expresses in phenotype; recessive allele expresses only when homozygous.

  • Particulate theory of inheritance vs blending; Mendel showed discrete units (alleles) govern traits.

Genetic Analysis Through Mutants

  • Mutants help identify genes influencing a property (gene discovery).

  • Wild-type (WT): normal form; Mutant: altered form of a property.

  • Examples: floral development in Arabidopsis thaliana; growth patterns in Neurospora crassa.

History of Inheritance Theories

  • Pangenesis: traits transmitted via seeds from all body parts (Hippocrates).

  • Preformationism: miniature preformed organism (homunculus) in the sperm or egg.

  • Blending theory: parental traits subtly mix in offspring; later disproven by Mendel's results.

Mendel's Experiments and Key Ratios

  • Founder of genetics; experiments with garden peas; results: Law of Segregation and Law of Independent Assortment.

  • Mendel’s work published in 1866; rediscovered in 1900 by de Vries, Correns, and von Tschermak.

  • Monohybrid crosses revealed two trait variants per character and the ~3:1 phenotypic ratio in F2.

  • Monohybrid cross example ratio: ext{Phenotypic ratio} = 3:1, ext{Genotypic ratio} = 1:2:1.

Crosses: Monohybrid Cross and Punnett Squares

  • Two cross types: Self-fertilization (P) and Cross-fertilization (P × P).

  • Punnett square predicts offspring genotypes; for tall (T) vs dwarf (t) with Tt × Tt:

  • Genotypic ratio: 1:2:1; Phenotypic ratio: 3:1 (tall: dwarf).

Chromosomal Basis of Mendelian Inheritance: Diploids

  • Somatic cells: diploid, two sets of chromosomes; end of S-phase: chromosomes replicated as sister chromatids; 2n chromosomes total.

  • Humans: 2n = 46.

  • G1: cell growth; S: DNA replication; G2: preparation for mitosis.

  • Homologous chromosomes pair during meiosis, but somatic cells undergo mitosis.

  • Sex chromosomes: XX in females, XY in males; X-chromosome carries many genes; Y-chromosome small set of genes.

Stages of Mitosis and Mitosis Outcomes **

  • Mitosis: produces two diploid daughter cells identical to mother (except rare mutations).

    • interphasse

    • prophase

    • metaphase

    • anaphase

    • telophase

  • Essential for growth, development, regeneration; cytokinesis completes cell division.

  • Maristem (stem cell): products of mitotic division, maintain genetic material, can become any cell from skin to nerve

Meiosis: Reduction and Recombination

  • Meiosis I (reductional) halves chromosome number; Meiosis II (equational) separates sister chromatids.

  • End results: four haploid gametes; genetic variation via homologous recombination.

  • Synaptonemal complex forms during prophase I; crossing over (chiasmata) increases genetic variation.

  • Meiocytes: 2n; produced by testes and ovaries

    • undergo meiosis during puberty

  • Adding “I or II” after a phase of mitosis implies meiosis

Haploids and Yeast Example (Saccharomyces cerevisiae)

  • Observed equal segregation within meiocytes; mating types MATa and MATα.

  • Wild-type r+ (white); Mutant r (red).

  • Tetrad analysis in asci shows 1:1 segregation of alleles: 1:1:1:1 in gametes within an ascus.

DNA-Level Alleles and RFLP

  • Restriction enzymes cut DNA at specific sequences; RFLP detects variation in restriction patterns.

  • RFLP uses a DNA probe to detect differences in fragments via Southern blot.

  • Example: PKU gene variants can be shown as normal vs mutant at the DNA level.

Gene Discovery by Segregation Analysis

  • Flower pigment example: white (alb/alb) vs red (+/+ or +/alb).

  • F1 crosses yield expected ratios; F2 confirms single dominant gene controlling pigment synthesis.

  • Conclusions: pigment controlled by a single dominant gene; gene likely involved in pigment biosynthesis or signaling.

Patterns of Mendelian Segregation: Sex Chromosomes

  • Humans: 2n = 46; female = XX; male = XY.

  • Differential regions of X and Y carry many genes; pseudoautosomal regions enable X-Y pairing in meiosis.

Patterns of Mendelian Segregation: X-Linked Inheritance - Monday

  • X-linked traits show distinctive patterns in pedigree and crosses.

  • Example: red-green color blindness in humans.

  • Features: no male-to-male transmission; affected males pass to all daughters (carriers if mother unaffected).

Patterns of Mendelian Segregation: X-Linked Dominant and Y-Linked

  • X-linked dominant: affected males transmit to all daughters but none of their sons; heterozygous affected females pass to half of both sons and daughters.

  • Y-linked: only males inherit; SRY gene determines maleness; transmission from father to all sons.

Pedigree Analysis and Probability in Genetics

  • Pedigree analysis traces segregation when controlled crosses are not possible.

  • Propositus: first individual with the phenotype in a family.

  • Probabilities guide predictions for offspring and genetic counseling.

  • Key formulas:

  • Sum Rule: Probabilities of mutually exclusive events add: P(A ext{ or } B) = P(A) + P(B).

  • Product Rule: Probabilities of independent events multiply: P(A ext{ and } B) = P(A) \cdot P(B).

  • Example: In dihybrid cross with independent assortment, phenotypic ratio is 9:3:3:1.

  • Example: congenital analgesia (recessive): for three children, probability all three are affected: \left(\frac{1}{4}\right)^3 = \frac{1}{64} \approx 0.016.

Autosomal Disorders: Recessive, Dominant, and Polymorphisms

  • Autosomal recessive: PKU; affected offspring from unaffected carrier parents; equal sex distribution.

  • Cystic fibrosis, albinism as examples of recessive alleles with carriers in population.

  • Autosomal dominant: Huntington disease; does not skip generations; many affected individuals are heterozygotes; can be de novo.

  • Polymorphisms: common autosomal variants with two or more phenotypes (e.g., dimorphism in eye color, PTC tasting).

X-Linked and Y-Linked Disorders: Highlights

  • X-linked recessive: more males affected; no male-to-male transmission; daughters of affected male are carriers.

  • X-linked dominant: rare; affected fathers transmit to all daughters but no sons; affected heterozygous females transmit to half of offspring.

  • Y-linked: present only in males; SRY and related male-determining genes.

Probability and Risk Assessment in Pedigree Analysis

  • Practical use: assess risk of genetic diseases for family planning.

  • Probability tools help genetic counselors provide guidance on likelihood of affected children.

  • Important to distinguish between independent vs mutually exclusive events in pedigrees.