Mendelian Genetics and Chromosomal Inheritance - Condensed Notes

Mendel established two fundamental laws from monohybrid crosses: Law of Segregation and Law of Independent Assortment; traits are controlled by discrete units (alleles) that segregate during gamete formation and assort independently for unlinked genes.
Alleles: dominant vs recessive; homozygous (two identical alleles) vs heterozygous (two different alleles).
Genotype vs phenotype: genotype is allelic composition; phenotype is outward appearance.
Particulate theory opposed blending; inheritance involves discrete factors (genes/alleles) transmitted via gametes.

Crosses with two alleles for a single trait yield genotypic ratio $1:2:1$ and phenotypic ratio $3:1$ when the trait shows complete dominance.
F1 generation from a cross between true-breeding parents is uniform for the dominant trait.
Punnett square predicts all possible offspring genotypes from parental gametes.

Diploids: somatic cells with two sets of chromosomes; haploids: gametes with one set.
DNA replication in S-phase produces sister chromatids; chromatid pairs remain joined at the centromere until separation in mitosis/meiosis.
Cells pass through cell cycle stages G1, S, G2, M (mitosis) or meiosis (sexual reproduction).

Mitosis produces two genetically identical diploid daughter cells; maintains chromosome number.
Key stages: Prophase, Metaphase, Anaphase, Telophase, followed by cytokinesis.
Ensures genetic stability across somatic cell generations; enables growth, development, and tissue repair.

Meiosis I reduces chromosome number from $2n$ to $n$ ; Meiosis II equational division yields four haploid gametes.
Two rounds of division: Meiosis I (reductional) and Meiosis II (equational).
Genetic variation arises from homologous recombination (crossing over) and independent assortment of homologs.
Synaptonemal complex forms during prophase I; crossing over creates recombinant chromosomes.
End of meiosis yields four genetically distinct haploid gametes.

Haploid models (e.g., Saccharomyces cerevisiae) show simple segregation of alleles in meiotic products (tetrads).
Mating types (MATa, MATα) illustrate distinct haploid states and chromosomal segregation.
RFLP (Restriction Fragment Length Polymorphism) and Southern blot are DNA-level techniques used to track single-gene inheritance.

PKU gene (PAH) mutations reduce or abolish phenylalanine hydroxylase activity, causing phenylalanine buildup.
Alleles at a locus can be wild-type or mutant; mutations can be determined by DNA-level assays.
Visual phenotype (PKU) correlates with underlying genotype, illustrating genotype-phenotype links.

Analyzing segregation in crosses (e.g., flower pigment) reveals whether a trait is controlled by a single dominant gene.
Conclusion examples: pigment controlled by a dominant allele; gene likely in pigment biosynthesis pathway or signaling that activates pigment production.

Autosomal: many traits follow standard Mendelian ratios for autosomal genes.
X-linked recessive: more males affected; no male-to-male transmission; daughters of affected male are carriers.
X-linked dominant: affected males pass to all daughters; less common; affected heterozygous females pass to half offspring.
Y-linked: traits passed from father to all sons; no female transmission; includes male-determining genes (e.g., SRY).
Pseudoautosomal regions enable X-Y pairing during meiosis.

Propositus: first individual in a family with the phenotype of interest.
Pedigree analysis helps infer inheritance pattern when controlled crosses are not possible.
Pedigrees illustrate autosomal recessive, autosomal dominant, X-linked recessive, X-linked dominant, and Y-linked patterns.

Example: Phenylketonuria (PKU) typically recessive; affected individuals often have unaffected carrier parents.
In small families, Mendelian ratios may deviate due to sampling; carriers are heterozygotes.
Consanguinity increases risk of homozygosity for recessive alleles.

Example: Pseudoachondroplasia (dwarfism) shows affected individuals in every generation; heterozygotes common.
De novo mutations can introduce dominant alleles.

X-linked recessive: more males affected; no male-to-male transmission; affected fathers pass to all daughters as carriers; color vision defects like red-green color blindness are classic examples.
X-linked dominant: rare; affected males transmit to all daughters; affected heterozygous females transmit to half of offspring.
Y-linked: only males; affected fathers pass to all sons; few genes mapped to Y chromosome (e.g., male-determining factors).

Probability (P) = (number of times event occurs) / (total number of events).
Sum Rule: P(A or B) = P(A) + P(B) for mutually exclusive events.
- Example: two independent phenotypes with 9:3:3:1 ratio; P(normal ears, normal tail) = $\frac{9}{16}$ ; P(droopy ears, crinkly tail) = $\frac{1}{16}$ ; combined probability = $\frac{9}{16} + \frac{1}{16} = \frac{10}{16} = 0.625$ .
Product Rule: P(A and B) = P(A) × P(B) for independent events.
- Example: congenital analgesia (recessive): two heterozygotes cross; P(congenital analgesia) = $\frac{1}{4}$ ; probability for three consecutive affected offspring = $\frac{1}{4} imes \frac{1}{4} imes \frac{1}{4} = \frac{1}{64}$ .
These rules underpin risk assessment in pedigrees and genetic counseling.