Genetics: Key Concepts, Laws, and Human Genetic Disorders

⭐ What is Genetics?

The study of heredity (trait passing), variation (why individuals differ), information flow (how DNA is encoded/copied/used), and evolution (genetic change over time in populations).

⭐ Three sub-disciplines of Genetics

1. Transmission Genetics - patterns of inheritance; 2. Molecular Genetics - DNA structure, replication, gene expression; 3. Population Genetics - allele frequencies and evolution.

Nehemiah Grew (1676)

Discovered sexual reproduction in plants using pollen.

Mendel (1800s)

Discovered laws of heredity using pea plants.

Weismann (1800s)

Proposed the germ-plasm theory.

Flemming (1800s)

Discovered chromosomes.

Darwin (1859)

Proposed evolution by natural selection.

Sutton (Early 1900s)

Proposed genes are located on chromosomes.

Morgan (Early 1900s)

Performed fruit fly experiments that confirmed genes are on chromosomes.

Why are model organisms used?

They are easy to grow/maintain, have short generation times, and are genetically well understood. Examples: bacteria, yeast, fruit flies, mice.

⭐ Gene

A unit of heredity; a stretch of DNA that codes for a protein.

⭐ Allele

A variant form of a gene.

⭐ Phenotype

The observable characteristic of an organism.

⭐ Genotype

The genetic makeup of an organism.

⭐ Prokaryotic vs Eukaryotic cells

Prokaryotic: no nucleus, single chromosome in nucleoid region, reproduce by binary fission (bacteria, archaea). Eukaryotic: have nucleus, multiple chromosomes packaged with proteins, larger and more complex (animals, plants, fungi).

⭐ Diploid (2n)

Two sets of chromosomes (most body cells). Humans: 2n = 46.

⭐ Haploid (n)

One set of chromosomes (usually gametes).

Eukaryotic Cell Cycle stages

1. Interphase (growth + DNA replication); 2. Mitosis (nuclear division); 3. Cytokinesis (cell division).

⭐ Mitosis vs Meiosis

Mitosis: produces identical daughter cells for growth/repair. Meiosis: produces gametes, divides TWICE, reduces chromosome number, increases genetic variation.

⭐ Central Dogma

DNA → RNA → Protein. DNA stores info, RNA carries instructions, Proteins produce traits.

⭐ Why did Mendel use pea plants?

Short generation time, large numbers of offspring, easily controlled matings, distinct observable traits.

⭐ Monohybrid cross

Cross between parents differing in ONE trait. F2 generation shows 3:1 dominant:recessive ratio.

⭐ Law of Segregation

Alleles separate during gamete formation (meiosis), so each gamete carries only ONE allele per gene.

⭐ Dihybrid cross

Cross between parents differing in TWO traits. F2 ratio is 9:3:3:1. Revealed the Law of Independent Assortment.

⭐ Law of Independent Assortment

Alleles of different genes assort independently during gamete formation.

⭐ Multiplication Rule (Probability)

Probability of two independent events BOTH occurring = product of individual probabilities.

Addition Rule (Probability)

Probability of one OR another event occurring = sum of individual probabilities.

⭐ Incomplete Dominance

Heterozygote shows an INTERMEDIATE phenotype (not fully dominant or recessive).

⭐ Chi-Squared Test (Goodness-of-Fit)

Tests if deviations from expected ratios are due to chance. Formula: χ² = Σ((observed − expected)² / expected). Small value = close to expected; Large value = far from expected.

⭐ XX-XY system

Females = XX; Males = XY. Found in humans.

⭐ ZZ-ZW system

Males = ZZ (homogametic); Females = ZW (heterogametic). Found in birds, snakes, butterflies.

XX-XO system

Females = XX; Males = X (no second sex chromosome). Found in some insects.

Haplodiploidy

Males = haploid (n); Females = diploid (2n). Found in bees, ants, wasps.

Environmental Sex Determination

Sex determined by environmental factors (e.g., temperature in bearded dragons overrides chromosomal sex).

Genic Sex Determination

Sex determined by alleles on autosomes — NO sex chromosomes involved. Found in some plants and protozoa.

⭐ Turner Syndrome (XO)

Phenotypic female, underdeveloped sex characteristics, sterile. Proves at least one X is essential.

⭐ Klinefelter Syndrome (XXY)

Phenotypic male (due to Y), reduced facial hair, small testes, sterile, often tall.

Poly-X Females (XXX, XXXX)

Phenotypically female, often tall/thin, may have fertility or cognitive issues.

⭐ SRY gene

Located on Y chromosome; triggers male development. Absence of Y → female phenotype.

⭐ X-Linked Recessive Traits

On X chromosome; males express recessive traits more (only one X). Example: red-green color blindness. Carrier mothers pass to sons.

Y-Linked traits

Inherited father to son only. Very rare (few genes on Y).

Androgen-Insensitivity Syndrome

Genotype XY but phenotype FEMALE. Defective androgen receptors; no response to testosterone. Shows SRY alone isn't enough for male development.

⭐ Nondisjunction

Failure of chromosomes to separate properly during meiosis → abnormal chromosome numbers.

⭐ Dosage Compensation

Mechanism to equalize X-gene expression between sexes. In mammals: one X is inactivated (Lyon hypothesis, 1961) forming a Barr body.

⭐ Barr Body

Inactive X chromosome visible in female cells. Proposed by Mary Lyon. Inactivation is random in each cell.

Tortoiseshell Cats

Patchy fur color due to random X-inactivation; orange fur allele is X-linked.

⭐ Penetrance

Fraction of individuals with a genotype who actually express the expected phenotype.

⭐ Expressivity

Degree of phenotype expression in an individual who does express the phenotype.

⭐ Epistasis

One gene masks or modifies the expression of another gene at a DIFFERENT locus. Epistatic gene = does the masking; Hypostatic gene = the one masked.

⭐ Multiple Alleles

A gene that has more than two alleles in a population. Each individual still carries only two. Examples: blood types, mallard duck plumage.

Lethal Alleles

Alleles that cause death in certain genotypes; alter expected Mendelian ratios.

⭐ Gene Interaction

Alleles from different loci affect the same trait. Independent assortment still applies; phenotypic ratios collapse.

Sex-Influenced Traits

Inherited by Mendel's laws but expressed differently in males vs females.

Sex-Limited Traits

Zero penetrance in one sex. Example: precocious puberty.

⭐ Cytoplasmic Inheritance

Genes in cytoplasm (mitochondria/chloroplasts), inherited from MOTHER only. Example: Four-O-Clock plants.

Genetic Maternal Effect

Offspring phenotype depends on mother's genotype; paternal alleles assort normally (different from cytoplasmic inheritance).

⭐ Genomic Imprinting

Reciprocal crosses yield different phenotypes; gene expression depends on which parent contributed the allele. Example: Igf2 gene.

⭐ Prader-Willi Syndrome

Caused by deletion inherited from FATHER (imprinting disorder).

⭐ Angelman Syndrome

Caused by same deletion inherited from MOTHER (imprinting disorder).

⭐ Autosomal Recessive pedigree pattern

Skips generations; affected individuals often have unaffected carrier parents; males and females equally affected; more common with consanguinity.

⭐ Autosomal Dominant pedigree pattern

Appears in every generation; individual usually has one affected parent; males and females equally affected; unaffected individuals don't pass trait.

⭐ X-Linked Recessive pedigree pattern

More common in males; never father-to-son; passed from carrier mothers to sons. Example: classic hemophilia.

X-Linked Dominant pedigree pattern

Affected fathers pass to daughters but NOT sons; more severe in males.

⭐ Monozygotic vs Dizygotic Twins

Monozygotic = identical (same genotype). Dizygotic = fraternal (share ~50% genes). Concordance comparison reveals genetic vs environmental contributions.

Concordance

Percentage of twin pairs that share a specific trait. Higher in MZ than DZ twins = genetic component.

Amniocentesis

Samples amniotic fluid containing fetal cells for genetic analysis.

Chorionic Villus Sampling (CVS)

Samples placenta tissue; can be performed earlier than amniocentesis.

⭐ Linked Genes

Genes on the same chromosome that tend to segregate together. Crossing over can separate them.

⭐ Recombination Frequency (RF)

% of recombinant progeny. Formula: (recombinants / total progeny) × 100%. Used to measure distance between genes.

⭐ Crossing Over

Occurs during Meiosis I; exchanges alleles between homologous chromosomes; produces recombinant gametes.

Coupling (cis)

Dominant alleles are on the SAME chromosome (AB/ab).

Repulsion (trans)

Dominant and recessive alleles on OPPOSITE chromosomes (Ab/aB).

⭐ Double Crossover

Crossing over at two points between genes. Two-stranded double crossover restores parental combinations → underestimates map distance.

⭐ Gene Mapping with 3 Genes (3-point cross)

1. Identify least frequent class = double crossovers; 2. Double crossovers reveal MIDDLE gene; 3. Determine gene order; 4. Calculate distances using RF.

⭐ Chi-squared test of independence

Used to detect linkage — compares observed offspring ratios to expected independent assortment ratios.

Alfred Sturtevant

Developed the first genetic map using Drosophila X chromosome.

McClintock & Creighton

Proved genes are physically on chromosomes; genetic recombination = physical chromosome exchange.

⭐ Types of chromosome mutations

1. Rearrangements (structure changes, same number); 2. Aneuploidy (gain/loss of single chromosomes); 3. Polyploidy (gain of whole sets).

⭐ Duplication

Chromosome segment is repeated (usually from unequal crossing over). Causes gene dosage imbalance. Example: Drosophila Bar Eye mutation.

⭐ Deletion

Loss of a chromosome segment. Can cause pseudodominance (recessive allele expressed when dominant is deleted) or haploinsufficiency.

⭐ Inversion (Paracentric vs Pericentric)

Segment flips 180°. Paracentric = doesn't include centromere → nonviable gametes (acentric/dicentric chromosomes). Pericentric = includes centromere → duplications/deletions in gametes.

⭐ Translocation

Segment moves to non-homologous chromosome. Reciprocal = exchange between two chromosomes. Robertsonian translocation = two acrocentric chromosomes fuse at centromere → familial Down syndrome.

⭐ Aneuploidy

Change in number of individual chromosomes. Types: Nullisomy (2n-2), Monosomy (2n-1), Trisomy (2n+1), Tetrasomy (2n+2). Caused by nondisjunction.

⭐ Trisomy 21 (Down Syndrome)

Extra copy of chromosome 21. Occurs in ~1/700 births. Primary = nondisjunction; Familial = Robertsonian translocation.

Trisomy 18 (Edwards Syndrome)

Extra chromosome 18; severe defects.

Trisomy 13 (Patau Syndrome)

Extra chromosome 13; severe defects.

⭐ Aneuploidy and Maternal Age

Risk increases with older maternal age due to long arrest of oocytes in prophase I.

⭐ Polyploidy

More than two complete chromosome sets. Autopolyploidy = same species. Allopolyploidy = hybridization of two species (common in plants, important in agriculture).

Genetic Mosaicism

Some cells normal, some aneuploid — caused by mitotic nondisjunction. Example: Mosaic Down Syndrome.

Uniparental Disomy (UPD)

Both copies of a chromosome from ONE parent; can cause imprinting disorders.

Fragile X Syndrome

Caused by trinucleotide repeat expansion at a fragile site; leads to intellectual disability.

⭐ Three methods of gene transfer in bacteria

1. Conjugation (direct DNA transfer via sex pilus); 2. Transformation (uptake of free DNA from environment); 3. Transduction (DNA transfer via bacteriophages).

⭐ Conjugation

Direct DNA transfer requiring cell-to-cell contact via sex pilus. F+ = donor; F- = recipient. Hfr cells transfer chromosomal genes. Discovered by Lederberg & Tatum. Can spread antibiotic resistance (R plasmids).

⭐ Transformation

Bacterium takes up free DNA from environment. Competent cells take up DNA; transformants have new DNA. Discovered by Frederick Griffith.

⭐ Transduction

DNA transfer via bacteriophages (viruses). Generalized = any gene transferred; Specialized = only specific genes. Discovered by Lederberg & Zinder.

⭐ F Factor (Fertility Plasmid)

Controls DNA transfer during conjugation. Types: F+, F-, Hfr (integrated into chromosome), F' (carries bacterial genes).

CRISPR-Cas (bacterial)

Adaptive immune system in bacteria. Steps: Adaptation → Expression → Interference. Basis for modern gene editing.

Restriction-Modification System

Bacteria cut foreign DNA using restriction enzymes to defend against phages.

⭐ DNA Supercoiling

Overwinding or underwinding of DNA helix. Topoisomerases control supercoiling and affect gene expression, replication, and stability.

⭐ Nucleosome

Basic unit of chromatin: DNA wraps around histone proteins. "Beads on a string." Histone H1 stabilizes.