Chromosomal Theory of Inheritance: The theory states that genes are located on chromosomes, and the behavior of chromosomes during meiosis accounts for Mendel's laws of inheritance.

Key Scientists:

1. Walter Sutton (1903) • Studied grasshopper chromosomes • Observed parallel behavior of chromosomes and Mendelian factors

2. Theodor Boveri (1903) • Studied sea urchin embryos • Showed chromosomes carry genetic information

3. Thomas Hunt Morgan (1910s) • Provided experimental proof using Drosophila • Discovered sex-linkage and genetic recombination • Won Nobel Prize (1933)

Key Evidence: • Chromosomes and genes both come in pairs • Homologous chromosome pairs separate during meiosis (explains Mendel's law of segregation) • Different chromosome pairs assort independently (explains Mendel's law of independent assortment) • Chromosome number is restored during fertilization

This unified cytology and genetics, explaining the physical basis of heredity.

Parental genotypes: Female (white eyes): XwXw Male (red eyes): X+Y

Gametes: Female produces: Xw only Male produces: X+ or Y

Punnett square: X+ Y Xw X+Xw XwY Xw X+Xw XwY

Offspring: Females: 100% X+Xw (red eyes, carriers) Males: 100% XwY (white eyes)

Phenotypic ratio: • All females: red eyes (2/4 = 50%) • All males: white eyes (2/4 = 50%)

This is a classic example of sex-linkage discovered by Morgan. The reciprocal cross (red female × white male) gives different results, proving the gene is on the X chromosome.

Key observation: Males show the recessive trait more frequently because they have only one X chromosome (hemizygous).

Mendel's Law of Independent Assortment: • Assumes genes are on different chromosomes • Each gene pair separates independently during meiosis • Predicts 9:3:3:1 ratio for dihybrid cross

Linked Genes (on same chromosome): • Do NOT assort independently • Tend to be inherited together • Produce parental combinations more frequently than recombinant types

Morgan's Discovery:

1. Found genes for body color and wing size in Drosophila were linked
2. Expected 1:1:1:1 from testcross, but got parental types > 50%
3. Explained by genes being on same chromosome

Modification to Mendelian genetics: • Genes on same chromosome = linked • Closer genes = more tightly linked (less recombination) • Crossing over can separate linked genes • Recombination frequency proportional to distance between genes • Led to chromosome mapping

General principle: • Genes on DIFFERENT chromosomes: independent assortment (50% recombination) • Genes on SAME chromosome: linkage (< 50% recombination) • Distance determines recombination frequency

This explained exceptions to Mendel's laws and showed chromosomal location matters!

Step 1: Identify parental vs recombinant types Testcross: AaBb × aabb

Offspring: AB: 450 } Parental types (most common) ab: 450 } Total = 900

Ab: 50 } Recombinant types (less common) aB: 50 } Total = 100

Step 2: Calculate recombination frequency Recombination frequency = (# recombinants / total offspring) × 100%

RF = (100 / 1000) × 100% = 10%

Step 3: Convert to map units 1% recombination = 1 map unit (m.u.) = 1 centimorgan (cM)

Map distance = 10 map units (or 10 cM)

Interpretation: • Genes A and B are 10 map units apart on the chromosome • 10% of gametes show recombination between these loci • Genes are linked but not tightly (moderate distance) • Crossing over occurs between them in 10% of meioses

Note: Maximum recombination frequency is 50% (for unlinked genes). Values < 50% indicate linkage.

Genomic Imprinting: A phenomenon where gene expression depends on which parent the allele came from. One allele is silenced based on parent of origin.

Violates Mendelian Genetics: • Mendel assumed both alleles contribute equally • Imprinting means maternal and paternal alleles are NOT equivalent • Phenotype depends on parent of origin, not just genotype

Mechanism: • Epigenetic modification (usually DNA methylation) • Occurs during gamete formation • Silences one allele while leaving the other active • Imprinting is "erased" and "reset" each generation

Human Example: Prader-Willi and Angelman Syndromes Both involve deletion on chromosome 15, but different phenotypes:

Prader-Willi Syndrome: • Deletion of paternal chromosome 15q11-13 • Symptoms: obesity, intellectual disability, short stature • Maternal copy is imprinted (silenced), so deletion of paternal copy = no gene expression

Angelman Syndrome: • Deletion of maternal chromosome 15q11-13 • Symptoms: severe intellectual disability, seizures, inappropriate laughter • Paternal copy is imprinted (silenced), so deletion of maternal copy = no gene expression

Same chromosomal region, different diseases depending on parent of origin!

Evolutionary significance: May reflect parent-offspring conflict over resource allocation.