2.5 Mendelian Genetics, Inheritance Patterns & Gene Mutations

2.5 Mendelian Genetics, Inheritance Patterns & Gene Mutations

Genetics explores the mechanism of heredity and variation. For pre-medical candidates taking the AMC test, high-yield topics include Mendelian ratios, non-Mendelian dominance relationships, X-linked inheritance, molecular mutations, and chromosomal aneuploidies.

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1. Mendelian Laws of Inheritance

Gregor Mendel established classical genetic principles through quantitative breeding experiments on garden peas (Pisum sativum).

A. Mendel's First Law: Law of Segregation

• States that during gamete formation, the two alleles of a gene locus segregate from each other so that each gamete carries only one allele.
• Cytological Basis: Separation of homologous chromosomes during Anaphase I of meiosis.
• Monohybrid Cross: Crossing homozygous tall ($TT$) with homozygous dwarf ($tt$) yields 100% heterozygous tall ($Tt$) in the $F_1$ generation. Selfing $F_1$ ($Tt \times Tt$) produces an $F_2$ generation with:
  • Phenotypic Ratio: $\mathbf{3\text{ Tall} : 1\text{ Dwarf}}$
  • Genotypic Ratio: $\mathbf{1\text{ } TT : 2\text{ } Tt : 1\text{ } tt}$

B. Mendel's Second Law: Law of Independent Assortment

• States that alleles of two or more different unlinked genes assort independently of one another into gametes.
• Cytological Basis: Random orientation of non-homologous chromosome pairs along the equatorial plate during Metaphase I of meiosis.
• Dihybrid Cross: Crossing $RRYY$ (round yellow) with $rryy$ (wrinkled green) produces an $F_2$ phenotypic ratio of $\mathbf{9 : 3 : 3 : 1}$.

C. Test Cross

• Crossing an individual exhibiting a dominant phenotype ($T_$) with a homozygous recessive individual ($tt$) to determine whether the dominant parent is homozygous ($TT$) or heterozygous ($Tt$).
  • If parent is $TT \times tt \rightarrow$ 100% dominant offspring.
  • If parent is $Tt \times tt \rightarrow$ $1:1$ ratio (50% dominant, 50% recessive).

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2. Non-Mendelian Allelic Interactions

Not all traits follow simple complete dominance patterns:

Dominance Spectrum:
[Complete Dominance] ──────> [Incomplete Dominance] ──────> [Codominance]
(PP = Pink, Pp = Pink)      (RR = Red, Rr = Pink, rr = White)   (IAIB = Both A & B expressed)

1. Incomplete Dominance: Heterozygote displays an intermediate, blended phenotype between both homozygous parental traits (e.g., 4 o'clock plant Mirabilis jalapa: Red $RR \times$ White $rr \rightarrow$ 100% Pink $Rr$; $F_2$ ratio = $1\text{ Red} : 2\text{ Pink} : 1\text{ White}$).
2. Codominance: Both alleles are fully and independently expressed in the heterozygote without blending (e.g., MN blood type; Sickle cell trait $Hb^A Hb^S$).
3. Multiple Alleles: A gene existing in more than two allelic forms within a population. Example: Human ABO Blood Group System governed by gene $I$ with three alleles ($I^A, I^B, i$):
   • $I^A$ and $I^B$ are codominant with each other, and both are completely dominant over allele $i$.
   • Genotypes & Phenotypes:
     • $I^A I^A$ or $I^A i \rightarrow$ Type A
     • $I^B I^B$ or $I^B i \rightarrow$ Type B
     • $I^A I^B \rightarrow$ Type AB (universal recipient)
     • $i i \rightarrow$ Type O (universal donor)
4. Polygenic Inheritance: Traits controlled by multiple additive genes, producing continuous quantitative variation (e.g., human skin color, height, intelligence).

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3. Sex Determination & Sex-Linked Inheritance

In humans, sex is determined by the XX-XY system (females $46,XX$; males $46,XY$). The Y chromosome carries the SRY gene (Sex-determining Region Y) triggering testis development.

X-Linked Recessive Inheritance:

• Traits carried on the X chromosome that are masked by a dominant allele in females.
• Key Characteristics: Affects males far more frequently than females (males are hemizygous $X^b Y$). Affected males inherit the mutant allele from carrier mothers (Criss-Cross Inheritance).
• High-Yield Examples:
  1. Red-Green Color Blindness: Deficiency in cone opsin photopigments.
  2. Hemophilia A & B: Bleeding disorders caused by deficiency of Factor VIII (Hemophilia A) or Factor IX (Hemophilia B).
  3. Duchenne Muscular Dystrophy: Progressive muscle degeneration due to defective dystrophin protein.

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4. Gene Mutations (Point Mutations)

Gene mutations are alterations in the base sequence of DNA at a single gene locus.

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5. Chromosomal Aberrations & Human Genetic Disorders

Structural or numerical alterations in chromosomes caused by nondisjunction (failure of homologous chromosomes or sister chromatids to separate during meiosis).

Nondisjunction in Meiosis ──> Gametes with n+1 or n-1 ──> Fertilization ──> Aneuploidy
                                                                           ├── Trisomy (2n + 1)
                                                                           └── Monosomy (2n - 1)

Numerical Chromosomal Disorders (Aneuploidy):

1. Down Syndrome (Trisomy 21):
   • Karyotype: $47, XX, +21$ or $47, XY, +21$ (Autosomal trisomy).
   • Features: Flat facial profile, epicanthic folds, simian crease across palm, mental retardation, congenital heart defects. Risk strongly correlates with advancing maternal age.
2. Turner Syndrome (Monosomy X):
   • Karyotype: $45, X0$ (Sex chromosome monosomy; female phenotype).
   • Features: Short stature, webbed neck, broad shield chest, rudimentary streak ovaries, primary amenorrhea, sterility.
3. Klinefelter Syndrome:
   • Karyotype: $47, XXY$ (Sex chromosome trisomy; male phenotype).
   • Features: Tall stature, long limbs, gynecomastia (enlarged breasts), small testes, sparse body hair, sterility.