17.4 Mendelian & Non-Mendelian Inheritance

Mendelian & Non-Mendelian Inheritance

Quick Answer: Mendel's two laws — segregation and independent assortment — explain monohybrid (3:1) and dihybrid (9:3:3:1) ratios. Non-Mendelian patterns modify these expectations: codominance (both alleles fully expressed, as in AB blood type), incomplete dominance (intermediate phenotype), epistasis, pleiotropy, mitochondrial inheritance, and genomic imprinting. The PA-CAT Bulletin of Information, rev. 20240815 pairs codominance with a worked AO × BO → AB sample item.

Mendel's Laws

1. Law of segregation: the two alleles of a gene separate during gamete formation; each gamete receives one allele. Cytological basis: anaphase I of meiosis separates homologs, so each gamete gets only one of the two homologs (and thus one allele per locus).
2. Law of independent assortment: alleles of genes on different (non-homologous) chromosomes assort independently. Cytological basis: metaphase I orientation of homologous pairs is random with respect to one another. Genes on the same chromosome may violate this (linkage; see Section 17.5).

Mendel's work used garden peas (Pisum sativum): controlled crosses, large offspring counts, and true-breeding lines made the ratios visible. His 1866 paper was rediscovered in 1900 by de Vries, Correns, and von Tschermak.

Monohybrid and Dihybrid Crosses

A monohybrid cross tracks one trait. Aa × Aa:

Genotype ratio 1 AA : 2 Aa : 1 aa; phenotype ratio 3 dominant : 1 recessive.

A dihybrid cross tracks two traits. AaBb × AaBb yields the 9:3:3:1 phenotypic ratio: 9 both dominant : 3 dominant at A, recessive at B : 3 recessive at A, dominant at B : 1 both recessive. This ratio assumes the two genes are unlinked (on different chromosomes or far apart on the same one).

A testcross (organism with dominant phenotype × homozygous recessive) reveals whether the dominant organism is homozygous (all dominant offspring) or heterozygous (1:1 dominant:recessive). A backcross to a parent reveals genotype similarly.

Probability Rules Applied to Genetics

• Product rule: probability of two independent events both occurring = P(A) × P(B). Two carrier parents (Aa × Aa) both passing the recessive allele: 1/2 × 1/2 = 1/4 affected child.
• Sum rule: probability of either of two mutually exclusive events = P(A) + P(B). Probability of AA or Aa in Aa × Aa = 1/4 + 1/2 = 3/4 dominant phenotype.

These rules extend to pedigrees. Autosomal recessive inheritance: skips generations, equal sex distribution, affected offspring of carrier parents (~25%). Autosomal dominant: every generation affected, ~50% of children of an affected heterozygous parent (e.g., Huntington disease, achondroplasia, Marfan).

Dominance Relationships

• Complete dominance: heterozygote phenotype = dominant homozygote. The recessive allele is masked but not absent.
• Incomplete dominance: heterozygote is intermediate. Red (RR) × white (rr) snapdragons → pink (Rr); F2 ratio 1:2:1 red:pink:white, so phenotype directly reflects genotype.
• Codominance: both alleles fully and simultaneously expressed, not blended. Classic case: ABO blood group.

Worked Cross: ABO Blood Type (PA-CAT Bulletin Codominance Sample Item)

The PA-CAT Bulletin of Information, rev. 20240815 provides a sample item: a mother with blood type AO and a father with blood type BO can produce an AB infant. The IA and IB alleles are codominant — both fully expressed — while i (O) is recessive to both.

Punnett square for IAi (A phenotype) × IBi (B phenotype):

Offspring phenotypes: 1 AB : 1 A : 1 B : 1 O (25% each). The AB outcome is possible only because IA and IB are codominant; neither masks the other. This is the Bulletin's canonical codominance illustration. Contrast with a cross of IAIB × ii, which yields 1:1 A:B (no AB possible, because the i parent contributes only i).

Epistasis and Pleiotropy

• Epistasis: one gene masks another. In the Bombay (hh) phenotype, the FUT1 enzyme (H antigen) is absent, so even genotypically A or B individuals type as O because they cannot display A/B antigens without the H substrate.
• Recessive epistasis in Labrador coat color: E gene permits pigment deposition; ee masks B/b → yellow Labs regardless of B genotype (9:3:4 ratio in BbEe × BbEe).
• Dominant epistasis (12:3:1): one dominant allele at one locus masks the second.
• Duplicate recessive (9:7): either homozygous recessive masks the trait — Combs on chickens.
• Pleiotropy: one gene affects multiple traits. Marfan syndrome (FBN1) → tall stature, long limbs, lens dislocation, aortic aneurysm risk — one gene, many effects.

Mitochondrial and Imprinted Inheritance

• Mitochondrial inheritance: strictly maternal (all mitochondria inherited from the egg); mtDNA is multicopy, no recombination, high mutation rate (no proofreading). Disorders show maternal transmission to all offspring but variable expression due to heteroplasmy (mixed mutant and normal mtDNA). Examples: Leber hereditary optic neuropathy (LHON), MELAS, MERRF.
• Genomic imprinting: allele expression depends on parent of origin, set by DNA methylation at imprinting control regions during gametogenesis. At 15q11-q13: paternal deletion → Prader-Willi syndrome (hyperphagia, hypotonia, intellectual disability); maternal deletion → Angelman syndrome (happy demeanor, seizures, ataxia) — same region, opposite phenotypes depending on which parent's copy is missing. Uniparental disomy (inheriting both copies from one parent) can produce the same syndromes.

Trinucleotide Repeat Disorders

Anticipation (increasing severity/earlier onset in successive generations) characterizes trinucleotide repeat expansion disorders: Huntington disease (CAG, HTT), fragile X (CGG, FMR1), myotonic dystrophy (CTG, DMPK). Fragile X is the most common inherited cause of intellectual disability.

PA-CAT Application

Distinguish codominance (both alleles visible in the heterozygote) from incomplete dominance (blended intermediate). Be ready to compute offspring ratios from a given cross and to identify epistasis from a modified dihybrid ratio (9:7, 9:3:4, 12:3:1). Recognize mitochondrial (maternal, all children) vs. X-linked recessive (maternal carrier, affected sons) pedigree patterns.