Chapter 10: Principles of Inheritance and Variation

Introduction

Overview

• Genetics studies inheritance and variation of traits from parents to offspring.
• Inheritance: transfer of traits from parent to progeny; basis of heredity.
• Variation: differences between progeny and parents.
• Early agriculturists (8000-1000 BC) used natural variations in sexual reproduction for selective breeding.
• Domesticated varieties developed by crossing wild plants and animals (e.g., Sahiwal cows from wild ancestors).
• Gregor Johann Mendel: Father of genetics.
• William Bateson coined the term "genetics."

Memory Aids

• Mendel = Father of Genetics.
• Bateson = Term "Genetics."
• Selective breeding exploits natural variation.

Quick Checkpoints

• What is the difference between inheritance and variation?
• Who is known as the Father of Genetics?
• How did early agriculturists use variation?

Mendel's Laws of Inheritance

Key Points

• Gregor Mendel studied inheritance using garden pea (Pisum sativum) from 1856-1863.
• Studied traits with two contrasting forms (e.g., tall/dwarf, yellow/green seeds).
• Used true-breeding pea lines that show stable traits after self-pollination.
• Selected 14 true-breeding varieties differing in one contrasting trait each.
• Reasons for choosing pea plant:
  • Annual plant with short 2-3 month life cycle.
  • Many contrasting traits available.
  • Natural self-pollination present.
  • Artificial cross-pollination possible for hybridisation.
  • Easy to cultivate.
  • Produces many seeds.

Memory Aids

• Pea plant traits: contrasting and easy to study.
• True-breeding lines ensure trait stability.
• Short life cycle speeds experiments.

Quick Checkpoints

• Why was Pisum sativum chosen for Mendel's experiments?
• What is a true-breeding line?
• What traits did Mendel study in peas?

Inheritance of One Gene

Observations and Results

• Mendel crossed tall and dwarf pea plants to study inheritance of one gene.
• Seeds from this cross grew into F9 generation (first hybrid generation).
• All F9 plants were tall, resembling one parent; dwarf trait was not seen.
• Self-pollination of F9 tall plants produced F2 generation with both tall and dwarf plants.
• In F2, 3/4 plants were tall and 1/4 were dwarf.
• Traits showed no blending; offspring were either tall or dwarf.
• Similar results for other traits: F9 resembled one parent, F2 showed both traits in 3:1 ratio.

Memory Aids

• F9 = first hybrid, shows dominant trait only.
• F2 = second generation, shows 3:1 dominant to recessive ratio.
• No blending means traits remain distinct.

Quick Checkpoints

• What trait appears in F9 generation?
• What is the phenotypic ratio in F2 generation?
• Does blending occur in these traits?

Genetics Terminology

Key Terms

• Alleles: Different forms of the same gene.
• Homozygous: Organism with identical alleles (e.g., TT, tt).
• Heterozygous: Organism with different alleles (e.g., Tt).
• Monohybrid cross: Cross between homozygous tall (TT) and dwarf (tt) producing heterozygous tall (Tt).
• Dominant allele: Expresses in homozygous or heterozygous state (e.g., T for tall).
• Recessive allele: Expresses only in homozygous state (e.g., t for dwarf).
• Phenotype: Observable traits influenced by genotype and environment.
• Genotype: Genetic makeup of an organism for a trait.

Memory Aids

• Dominant allele masks recessive in heterozygotes.
• Homozygous = same alleles; heterozygous = different alleles.
• Phenotype = what you see; genotype = genetic code.

Quick Checkpoints

• Define homozygous and heterozygous.
• What is a monohybrid cross?
• Difference between dominant and recessive alleles?

Punnett Square Method

Concept and Usage

• Developed by Reginald C. Punnett to predict offspring genotypes.
• Graphical tool to calculate probability of genotypes in genetic crosses.
• Test cross: Cross between unknown genotype and recessive parent to determine genotype.
• Helps analyze progeny to predict genotype of dominant phenotype organism.

Memory Aids

• Test cross uses recessive parent to reveal unknown genotype.
• Punnett square = probability grid for offspring genotypes.

Quick Checkpoints

• What is the purpose of a Punnett square?
• How does a test cross help determine genotype?

Laws of Inheritance

Principles by Mendel

• First Law: Law of Dominance - dominant allele expresses in heterozygote.
• Second Law: Law of Segregation - alleles separate during gamete formation.
• Traits do not blend; recessive traits reappear in F2 generation.

Memory Aids

• Dominance: one allele masks the other.
• Segregation: alleles separate into different gametes.

Quick Checkpoints

• What does the Law of Dominance state?
• Explain the Law of Segregation.
• Why do recessive traits reappear in F2?

Incomplete Dominance

Definition and Example

• Neither allele is dominant; heterozygote shows intermediate phenotype.
• Example: Flower color in Antirrhinum (snapdragon).
• Cross of red (RR) and white (rr) flowers produces pink (Rr) flowers in F9.
• F2 generation shows 1 red : 2 pink : 1 white ratio in both genotype and phenotype.

Memory Aids

• Incomplete dominance = blend of traits in heterozygote.
• Phenotypic ratio equals genotypic ratio in incomplete dominance.

Quick Checkpoints

• What is incomplete dominance?
• How does flower color inheritance in snapdragon illustrate this?
• What is the phenotypic ratio in F2 generation?

Co-dominance

Definition and Example

• Both alleles express simultaneously in heterozygote.
• Example: ABO blood group in humans controlled by gene with alleles I^A, I^B, and i.
• I^A and I^B are dominant over i; when together, both express (blood group AB).
• Multiple alleles: more than two alleles exist in population but individual has only two.
• Single gene can have multiple effects (pleiotropy), e.g., starch synthesis in pea seeds.

Memory Aids

• Co-dominance = both alleles visible in phenotype.
• Multiple alleles exist in population, not in individual.
• Dominance depends on gene product and phenotype.

Quick Checkpoints

• What is co-dominance?
• Explain ABO blood group inheritance.
• What is multiple alleles?

Law of Independent Assortment

Explanation

• Mendel crossed pea plants differing in two traits: seed colour (yellow dominant over green) and seed shape (round dominant over wrinkled).
• Parental genotypes: RRYY (round yellow) × rryy (wrinkled green).
• F1 generation: All RrYy (round yellow) from RY and ry gametes.
• F2 generation phenotypic ratio: 9 round yellow : 3 wrinkled yellow : 3 round green : 1 wrinkled green.
• Segregation of one gene pair is independent of the other pair.
• Segregation of R and r gametes is independent of Y and y gametes.
• Applicable only to genes on different chromosomes or far apart on the same chromosome.

Memory Aids

• Independent segregation = genes assort independently if on different chromosomes or far apart.
• Phenotypic ratio 9:3:3:1 in dihybrid cross.
• Use symbols: Y/y for seed colour, R/r for seed shape.

Quick Checkpoints

• What is the phenotypic ratio in a dihybrid cross?
• When does independent assortment apply?
• What are the parental genotypes in Mendel’s dihybrid cross?

Dihybrid Test Cross

Explanation

• Cross between F1 dihybrid (TtRr) and recessive parent (ttrr).
• F1 produces four gametes: TR, Tr, tR, tr; recessive parent produces tr only.
• Offspring genotypes: TtRr, Ttrr, ttRr, ttrr in equal proportions.
• Phenotypic ratio: 1 : 1 : 1 : 1.

Memory Aids

• Test cross reveals genotype by crossing with recessive homozygote.
• Dihybrid test cross ratio always 1:1:1:1.

Quick Checkpoints

• What gametes does an F1 dihybrid produce?
• What is the phenotypic ratio in a dihybrid test cross?
• Why is the recessive parent used in test cross?

Intergenic Interaction

Explanation

• Effect of one gene modified by another non-allelic gene at different locus.
• Types:
• Complementary genes: Two genes produce new trait together; F2 ratio 9:7.
• Supplementary genes: One gene’s effect depends on presence of another; F2 ratio 9:3:4.
• Epistasis: One gene masks expression of another.
• Pleiotropy: One gene affects multiple phenotypes.

Memory Aids

• Complementary = both needed for trait.
• Supplementary = one gene supports another.
• Epistasis = gene masking.
• Pleiotropy = one gene, many effects.

Quick Checkpoints

• What is complementary gene interaction?
• Define epistasis.
• What is pleiotropy?

Chromosomal Theory of Inheritance

Explanation

• Mendel’s work initially unrecognized due to communication, acceptance, and lack of physical proof.
• Rediscovered in 1900 by Correns, de Vries, and von Tschermak.
• Theory proposed by Sutton and Boveri in 1902; proved by T.H. Morgan in 1933.
• Chromosomes behave like Mendelian factors during meiosis.
• Key points:
• Sperm and egg contribute equally.
• Chromosomes carry hereditary traits.
• Chromosomes retain number, structure, individuality.
• Chromosomes and genes occur in pairs in diploid cells.
• Alleles located on homologous chromosomes.
• Chromosome pairs align independently during metaphase I.
• Chromosome segregation explains gene segregation.
• Chromosomal explanation of law of segregation: Homologous chromosomes separate in meiosis I; chromatids separate in meiosis II.

• Morgan used Drosophila melanogaster for genetic studies due to:
• Easy lab culture.
• Short life cycle (~2 weeks).
• Large progeny numbers.
• Distinct male and female flies.
• Visible hereditary variations.

Memory Aids

• Chromosomes = carriers of genes.
• Segregation explained by chromosome separation.
• Drosophila ideal for genetics due to fast breeding and visible traits.

Quick Checkpoints

• Who proposed the chromosomal theory of inheritance?
• How does chromosome behavior explain Mendel’s laws?
• Why is Drosophila melanogaster used in genetics?

Linkage and Recombination

Explanation

• Morgan’s dihybrid crosses in Drosophila showed deviation from 9:3:3:1 ratio.
• Genes on same chromosome tend to be inherited together (linkage).
• Linkage: physical association of genes on a chromosome.
• Recombination: production of non-parental gene combinations.
• Linkage groups = genes on same chromosome; number equals haploid chromosome number.
• Complete linkage: no crossing over, genes inherited together.
• Incomplete linkage: crossing over occurs, producing parental and recombinant types.
• Recombination frequency indicates gene distance.
• Example: white and yellow genes tightly linked (1.3% recombination); white and miniature wing loosely linked (37.2%).
• Sturtevant used recombination frequency to map gene positions.

Memory Aids

• Linkage = genes close on chromosome inherited together.
• Recombination frequency = measure of gene distance.
• Complete linkage = no recombination; incomplete linkage = some recombination.

Quick Checkpoints

• What causes deviation from 9:3:3:1 ratio in dihybrid crosses?
• Define linkage and recombination.
• How is recombination frequency used in gene mapping?

Polygenic Inheritance

Explanation

• Inheritance controlled by three or more genes is polygenic inheritance.
• Phenotype reflects additive effect of each allele.
• Examples: human skin colour, height, wheat kernel colour.
• Human skin colour depends on melanin pigment quantity controlled by three gene pairs (A, B, C).
• Genotype AABBCC = darkest skin; all recessive alleles = lightest skin; mixed alleles = intermediate skin colour.
• Thomas Hunt Morgan's crosses show gene linkage on chromosomes (genes y, w, m).

Memory Aids

• Polygenic = many genes add up effects.
• Skin colour = sum of dominant alleles.
• More dominant alleles = darker skin.

Quick Checkpoints

• What defines polygenic inheritance?
• How does allele contribution affect phenotype?
• Which genes control human skin colour?
• What is the effect of dominant vs recessive alleles on skin colour?

Pleiotropy

Explanation

• Single gene influences multiple traits.
• Gene affects inter-related metabolic pathways producing different phenotypes.
• Example: Phenylketonuria caused by mutation in phenylalanine hydroxylase gene.
• Results in mental retardation and reduced hair and skin pigmentation.

Memory Aids

• Pleiotropy = one gene, many effects.
• Phenylketonuria = single gene mutation, multiple symptoms.

Quick Checkpoints

• What is pleiotropy?
• How does one gene affect multiple traits?
• What causes phenylketonuria?
• What are the symptoms of phenylketonuria?

Sex Determination

Overview

• Sex determination establishes male and female distinction in species.
• Determined by sex chromosomes (allosomes): X and Y chromosomes.
• Non-sex chromosomes are autosomes.
• Henking discovered X-body in 50% of sperm in some insects.

Memory Aids

• Sex chromosomes = Allosomes (X & Y).
• Autosomes = all other chromosomes.
• Henking’s X-body = early sex chromosome discovery.

Quick Checkpoints

• What are sex chromosomes?
• Difference between autosomes and allosomes?
• Who discovered the X-body?

Types of Chromosomal Sex Determination

XX–XY type

• Female: homogametic (XX), produces one type of gamete (X).
• Male: heterogametic (XY), produces two types of gametes (X = gynosperm, Y = androsperm).
• Both sexes have same autosome number.
• Found in humans and Drosophila.

XX–XO type

• Males have one sex chromosome (X), heterogametic; some sperms have X, some none.
• Females are homogametic (XX).
• Fertilisation with X sperm = female (2A + XX); without X = male (2A + XO).
• Found in grasshopper, cockroach, roundworms.

ZW–ZZ type

• Female: heterogametic (ZW), produces Z and W gametes.
• Male: homogametic (ZZ), produces Z gametes.
• Found in birds and some reptiles.
• ZO–ZZ type: females (AA + Z), males (AA + ZZ), found in butterflies and moths.

Memory Aids

• XX–XY: Male heterogametic, female homogametic.
• XX–XO: Male heterogametic with single X.
• ZW–ZZ: Female heterogametic, male homogametic.

Quick Checkpoints

• Which sex is homogametic in XX–XY?
• What determines sex in XX–XO type?
• Where is ZW–ZZ system found?

Haploid–Diploid Mechanism of Sex Determination

Mechanism

• Observed in Hymenoptera (ants, honeybees, wasps).
• Sex depends on chromosome set number.
• Females (queen, workers) develop from fertilised (diploid) eggs.
• Males (drones) develop from unfertilised (haploid) eggs by parthenogenesis.
• Males have 16 chromosomes (haploid), females 32 (diploid).
• Male sperms formed by mitosis, no meiosis.
• Males have no father, but have grandfather; can have grandsons.

Memory Aids

• Haploid males from unfertilised eggs.
• Diploid females from fertilised eggs.
• No meiosis in male sperm formation.

Quick Checkpoints

• Which insects show haploid-diploid sex determination?
• How are male and female chromosome numbers different?
• How are male sperms produced?

Sex Determination in Humans

Mechanism

• Humans use XY system.
• 22 pairs autosomes identical in males and females.
• Females have XX; males have XY chromosomes.
• Males produce two sperm types: 50% X-chromosome, 50% Y-chromosome.
• Females produce only X-chromosome ova.
• Fertilisation with X sperm = female (XX); with Y sperm = male (XY).
• Sex determined by sperm chromosome.
• Equal chance of male or female child per pregnancy.
• Sex-linked inheritance: genes on sex chromosomes inherited with sex traits.
• Sex-linked traits more visible in males; females often carriers (e.g., colour blindness, haemophilia).
• Criss-cross inheritance: traits passed to same-sex grandchild via opposite-sex parent.

Memory Aids

• XY system: male heterogametic, female homogametic.
• Sperm chromosome determines sex.
• Sex-linked traits show criss-cross inheritance.

Quick Checkpoints

• What chromosomes determine human sex?
• How does sperm type affect sex?
• What is criss-cross inheritance?

Mutation

Types and Effects

• Mutation alters DNA sequences, changing genotype and phenotype.
• Both recombination and mutation cause DNA variation.
• Loss or gain of DNA segments alters chromosomes, causing abnormalities.
• Chromosomal aberrations are common in cancer cells.
• Chromosomal mutations include:
  • Deletion: Loss of chromosome segment (terminal or intercalary).
  • Duplication: Repetition of gene blocks in haploid set.
  • Translocation: Exchange of segments between non-homologous chromosomes.
  • Inversion: Chromosome segment breaks, rotates 180°, and rejoins reversed.
  • Euploidy: Gain or loss of complete chromosome sets; types: monoploidy, polyploidy.
  • Aneuploidy: Gain or loss of individual chromosomes; types: trisomy, tetrasomy, monosomy, nullisomy.
• Gene mutations occur naturally or internally.
• Point mutation: Change in single base pair (e.g., sickle cell anaemia).
• Frame-shift mutation: Caused by insertions or deletions of base pairs.
• Mutagens: Chemical or physical agents inducing mutations (e.g., UV radiation).

Memory Aids

• Deletion = DNA segment lost.
• Duplication = DNA segment repeated.
• Translocation = Swap between non-homologous chromosomes.
• Inversion = Segment flipped 180°.
• Euploidy = Whole set change; Aneuploidy = Single chromosome change.
• Point mutation = Single base change.
• Frame-shift = Insertions/deletions shift reading frame.
• Mutagens = Mutation-causing agents.

Quick Checkpoints

• What causes chromosomal aberrations?
• Define deletion and duplication mutations.
• Explain translocation and inversion.
• Differentiate euploidy and aneuploidy.
• What is a point mutation?
• How do frame-shift mutations occur?
• Give examples of mutagens.

Genetic Disorders Pedigree Analysis

Explanation

• Pedigree is a chart showing inheritance of traits across generations in humans or animals.
• It helps deduce genotypes from phenotypes and study inheritance patterns of dominant/recessive traits or diseases.
• Genetic disorders arise from altered genes or chromosomes.
• Two main categories: Mendelian disorders and Chromosomal disorders.

• Symbols in pedigree: squares (males), circles (females), diamonds (unspecified sex).
• Filled shapes indicate affected individuals.
• Single line = mating; double line = mating between relatives.
• Vertical lines connect parents to children.
• Special symbols for carriers, deceased, stillbirths, twins.
• Roman numerals for generations; Arabic numerals for individuals.

Memory Aids

• Square = Male, Circle = Female, Filled = Affected
• Single line = Mating, Double line = Consanguineous mating
• Roman numerals = Generations, Arabic numerals = Individuals

Quick Checkpoints

• What does a filled circle represent?
• How is consanguineous mating shown?
• What information does a pedigree provide?

Mendelian Disorders

Explanation

• Caused by mutation in a single gene.
• Inheritance pattern traced by pedigree analysis.
• Examples: haemophilia, cystic fibrosis, sickle-cell anaemia, colour blindness, phenylketonuria, thalassemia.
• Can be dominant or recessive; some are sex-linked (e.g., haemophilia is X-linked recessive).
• Carrier females transmit X-linked recessive traits to male offspring.

• Autosomal dominant: trait appears every generation if one parent affected.
• Autosomal recessive: trait appears when both parents carry gene, may skip generations.

Memory Aids

• Dominant traits appear in every generation.
• Recessive traits may skip generations.
• X-linked recessive traits mostly affect males.

Quick Checkpoints

• How to distinguish dominant vs recessive traits in pedigree?
• What is the inheritance pattern of haemophilia?
• Which disorders are Mendelian?

Colour Blindness

Explanation

• Sex-linked recessive disorder due to mutation in genes on X chromosome affecting red or green cones.
• Causes inability to distinguish red and green colors.
• Occurs in ~8% males, ~0.4% females due to males having one X chromosome.
• Carrier mothers have 50% chance of passing gene to sons.
• Daughters affected only if mother is carrier and father is colour blind.

Memory Aids

• Colour blindness gene is X-linked recessive.
• Males affected more due to single X chromosome.
• Carrier females usually unaffected.

Quick Checkpoints

• Why are males more affected?
• How is colour blindness inherited?
• What cones are affected?

Sickle-cell Anaemia

Explanation

• Autosomal recessive disorder caused by mutation in beta globin gene (Hbᴬ and Hbˢ alleles).
• Only homozygous HbˢHbˢ individuals show disease; heterozygous are carriers.
• Mutation substitutes glutamic acid by valine at 6th position of beta globin chain.
• Causes hemoglobin polymerisation under low oxygen, changing RBC shape to sickle.

• Normal RBCs are round and flexible; sickle cells are crescent-shaped and rigid.
• DNA change: normal gene CTC to sickle gene CAC.
• mRNA changes from GAG to GUG causing amino acid change Glu to Val.
• Results in sickle-cell anaemia symptoms.

Memory Aids

• Hbˢ allele causes sickle shape.
• Glu to Val substitution at 6th amino acid.
• Carriers are heterozygous, affected are homozygous.

Quick Checkpoints

• What amino acid substitution causes sickling?
• Which genotype shows disease?
• How does mutation affect RBC shape?

Haemophilia

Explanation

• Sex-linked recessive disorder affecting blood clotting protein.
• Carrier females transmit disease to male offspring.
• Causes prolonged bleeding from minor injuries.
• Female haemophilia is rare, requires carrier mother and affected father.
• Queen Victoria's pedigree shows haemophilia transmission.

Memory Aids

• X-linked recessive inheritance.
• Carrier females unaffected but transmit to sons.
• Causes bleeding due to clotting protein defect.

Quick Checkpoints

• How is haemophilia inherited?
• Why are males mostly affected?
• What causes bleeding in haemophilia?

Phenylketonuria

Explanation

• Autosomal recessive metabolic disorder.
• Lack of enzyme converting phenylalanine to tyrosine.
• Phenylalanine accumulates, converted to phenylpyruvic acid causing brain damage.
• Excess excreted in urine due to poor kidney absorption.

Memory Aids

• Autosomal recessive inheritance.
• Enzyme deficiency blocks phenylalanine metabolism.
• Causes mental retardation if untreated.

Quick Checkpoints

• Which enzyme is deficient?
• What accumulates in the body?
• How does it affect the brain?

Thalassemia

Explanation

• Autosomal recessive blood disorder from mutation or deletion affecting globin chain synthesis.
• Causes reduced synthesis of α, β, or δ globin chains leading to abnormal hemoglobin and anemia.
• Types: α-thalassemia (chromosome 16), β-thalassemia and δ-thalassemia (chromosome 11).
• Different from sickle-cell anemia: thalassemia is quantitative defect; sickle-cell is qualitative.

Memory Aids

• α-thalassemia: defective α-globin genes on chromosome 16.
• β-thalassemia: defective β-globin genes on chromosome 11.
• δ-thalassemia: defective δ-globin gene on chromosome 11.

Quick Checkpoints

• Which chromosomes carry globin genes?
• How does thalassemia differ from sickle-cell anemia?
• What causes anemia in thalassemia?

Chromosomal Disorders

Explanation

• Caused by absence, excess, or abnormal arrangement of chromosomes.
• Aneuploidy: gain or loss of chromosomes due to segregation failure (e.g., Down’s syndrome trisomy 21, Turner’s syndrome monosomy X).
• Polyploidy: failure of cytokinesis causing extra whole chromosome sets, common in plants.
• Normal human cells have 46 chromosomes (23 pairs): 22 autosomes + 1 pair sex chromosomes.
• Trisomy: extra chromosome; Monosomy: missing chromosome; both cause serious effects.

• Karyotype shows three copies of chromosome 21 in Down’s syndrome.
• Extra chromosome causes developmental and physical traits of syndrome.

• Down's Syndrome: trisomy 21, features include flat nasal bridge, small ears, short neck.
• Edward's Syndrome: trisomy 18, features include small mouth, clenched hands, abnormal skull.
• Turner's Syndrome: monosomy X, features include short height, broad chest, webbed neck.
• Klinefelter's Syndrome: extra X in males, features include sparse hair, small testes, breast development.

Memory Aids

• Aneuploidy = abnormal chromosome number.
• Trisomy = extra chromosome; Monosomy = missing chromosome.
• Down’s = trisomy 21; Turner’s = monosomy X; Klinefelter’s = XXY males.

Quick Checkpoints

• What is aneuploidy?
• Which chromosome is extra in Down’s syndrome?
• What causes Turner’s syndrome?