Difficulty: Intermediate | Prerequisites: Part 1 of these notes (history, Central Dogma); basic understanding of chromosomes and cell division
Before anyone knew that DNA was the molecule of heredity, Gregor Mendel worked out the rules of inheritance using pea plants in a monastery garden. His laws of segregation and independent assortment still form the foundation of genetics. This block builds outward from Mendel: first the simple patterns, then the complications (incomplete dominance, codominance, polygenic traits), then the physical basis of inheritance in mitosis and meiosis, and finally what happens when genes do not assort independently because they sit on the same chromosome (linkage, crossing over, genetic mapping). If you can trace alleles through crosses and understand why linked genes violate Mendel's second law, you are in good shape for exam questions.
Mendel's laws describe how alleles segregate during gamete formation and assort independently when on different chromosomes. Complications like incomplete dominance and codominance show that dominance is not always complete. Genes on the same chromosome are linked and tend to be inherited together unless crossing over separates them, and the frequency of recombination between two genes is used to map their distance apart.
Allele
One of two or more alternative forms of a gene at a given locus. In simple terms, alleles are different "versions" of the same gene.
Homozygous
Having two identical alleles at a given locus (e.g., AA or aa). Think of it as both copies of the gene matching.
Heterozygous
Having two different alleles at a given locus (e.g., Aa). Think of it as carrying one of each version.
Dominant
An allele whose phenotype is expressed in the heterozygote. Only one copy is needed for the trait to appear.
Recessive
An allele whose phenotype is expressed only when two copies are present (homozygous). In the heterozygote, the dominant allele masks it.
Genotype
The genetic makeup of an organism at one or more loci, written as allele combinations (e.g., Aa, BbCc).
Phenotype
The observable physical or biochemical characteristics of an organism, resulting from the interaction of genotype and environment. In simple terms, genotype is what the genes say; phenotype is what you actually see.
Diploid
A cell or organism containing two complete sets of chromosomes (2n), one from each parent.
Haploid
A cell or organism containing a single set of chromosomes (n). Gametes (sperm and egg) are haploid.
Autosomal trait
A trait encoded by a gene located on an autosome (any chromosome that is not a sex chromosome).
Sex-linked trait
A trait encoded by a gene located on a sex chromosome, most commonly the X chromosome. In simple terms, because males have only one X, a single recessive allele on the X will be expressed in males but hidden in carrier females.
Segregation (Mendel's First Law)
During gamete formation, the two alleles for a gene separate so that each gamete carries only one allele.
Independent assortment (Mendel's Second Law)
Genes on different chromosomes are distributed to gametes independently of one another during meiosis.
Incomplete dominance
A pattern of inheritance where the heterozygote shows a phenotype intermediate between the two homozygotes (e.g., red x white = pink in snapdragons).
Codominance
A pattern of inheritance where both alleles in a heterozygote are fully expressed simultaneously (e.g., AB blood type, where both A and B antigens appear on red blood cells).
Multiple alleles
More than two allele forms existing in a population for a given gene. Any individual still carries at most two (one per homologue), but the population has more options. The ABO blood group is a classic example with three alleles: I^A, I^B, and i.
Polygenic inheritance
A trait controlled by the additive effects of two or more genes, producing continuous variation (e.g., skin colour, height).
Gene linkage
The tendency of genes located on the same chromosome to be inherited together because they do not assort independently.
Crossing over (recombination)
The exchange of genetic material between homologous chromosomes during prophase I of meiosis. This breaks up linked genes and produces recombinant gametes.
Recombination frequency
The proportion of recombinant offspring out of total offspring in a cross. Used to estimate the distance between two genes on the same chromosome. In simple terms, the more often two genes get separated by crossing over, the farther apart they are.
Genetic map (linkage map)
A diagram showing the relative positions of genes on a chromosome based on recombination frequencies, measured in map units (1 map unit = 1% recombination frequency, also called a centimorgan).
Sutton's Chromosomal Theory of Inheritance
The theory that Mendel's factors (genes) are located on chromosomes, and the behaviour of chromosomes during meiosis accounts for Mendel's laws of segregation and independent assortment.
Mendel chose garden peas (Pisum sativum) because they had clearly distinct, heritable traits (flower colour, seed shape, plant height, etc.), could be self-fertilised or cross-fertilised, and produced large numbers of offspring.
Monohybrid cross: cross between parents differing in one trait (e.g., Tt x Tt). Expected phenotype ratio in F2: 3:1. Expected genotype ratio: 1:2:1.
Dihybrid cross: cross between parents differing in two traits (e.g., TtYy x TtYy). Expected phenotype ratio in F2: 9:3:3:1, assuming independent assortment.
Test cross: cross an individual showing the dominant phenotype with a homozygous recessive individual. The offspring ratios reveal the unknown genotype. If all offspring show the dominant phenotype, the parent was likely homozygous dominant. If roughly half show the recessive phenotype, the parent was heterozygous.
The probability method uses the multiplication rule (probability of two independent events both occurring = product of their individual probabilities) and the addition rule (probability of either of two mutually exclusive events = sum of their individual probabilities) to predict outcomes of crosses without drawing full Punnett squares.
First Law (Principle of Segregation): the two alleles of a gene separate during gamete formation, so each gamete receives one allele.
Second Law (Independent Assortment): alleles of different genes assort independently during gamete formation, provided those genes are on different chromosomes.
Sutton's Chromosomal Theory provided the physical basis: chromosomes pair up and segregate during meiosis I, and homologous pairs orient randomly at the metaphase plate, producing independent assortment.
Incomplete dominance: heterozygote phenotype is a blend. Cross two heterozygotes and you get a 1:2:1 phenotype ratio (not 3:1) because all three genotypes produce distinct phenotypes.
Codominance: both alleles are fully expressed in the heterozygote. Neither is "dominant" over the other.
Multiple alleles: the ABO blood group system has three alleles (I^A, I^B, i). I^A and I^B are codominant with each other; both are dominant over i.
Polygenic inheritance: many genes contribute small, additive effects. Phenotypes show continuous variation and often a bell-curve distribution in the population.
Mitosis produces two genetically identical daughter cells (2n → 2n). Its purpose is growth, repair, and asexual reproduction. No segregation of alleles occurs because homologues do not pair up.
Meiosis produces four genetically unique haploid cells (2n → n). It is the basis of sexual reproduction.
Meiosis I is the reductional division: homologous chromosomes pair (synapsis), crossing over occurs at chiasmata, and homologues segregate. This is where Mendel's First Law (segregation) and Second Law (independent assortment) play out physically.
Meiosis II resembles mitosis: sister chromatids separate.
Segregation occurs in meiosis I when homologous chromosomes move to opposite poles. Independent assortment occurs because the orientation of each homologous pair at the metaphase I plate is random and independent of every other pair.
When genes are on the same chromosome, they are linked and tend to be inherited together. Linked genes violate Mendel's Second Law because they do not assort independently.
Complete linkage: genes are so close on the chromosome that recombination between them almost never occurs. Offspring show only parental combinations.
Incomplete linkage: crossing over between linked genes does occur at some frequency, producing both parental-type and recombinant-type offspring.
X-linked traits are a specific case of linkage. Genes on the X chromosome show a distinctive pattern:
Males (XY) are hemizygous for X-linked genes; a single recessive allele is expressed.
Females (XX) can be carriers of X-linked recessive traits without showing the phenotype.
X-linked recessive traits appear more frequently in males (e.g., colour blindness, haemophilia).
Father-to-son transmission of X-linked traits does not occur, because fathers pass their Y chromosome to sons.
Janssen's Hypothesis of Crossing Over (1909): Frans Janssen observed chiasmata (X-shaped structures) during meiosis and proposed that they represented physical exchanges of chromosome segments between homologous chromosomes.
Barbara McClintock provided cytological evidence by studying maize chromosomes. She distinguished:
Non-crossover chromosomes: chromosomes that retained their original configuration, showing no exchange of markers.
Crossover chromosomes: chromosomes that showed new combinations of markers, confirming physical exchange had occurred at the sites Janssen observed.
Genetic mapping uses recombination frequencies to estimate the relative distance between genes on a chromosome.
Recombination frequency (RF) = (number of recombinant offspring / total offspring) x 100%.
1% recombination = 1 map unit (centimorgan, cM).
Genes with RF close to 50% behave as if unlinked (they may be on different chromosomes or very far apart on the same one).
Multiple crossovers: when two crossover events occur between two genes, they can cancel each other out (a double crossover restores the parental arrangement for the outermost markers). This means the observed recombination frequency underestimates the true distance for genes that are far apart.
Three-point crosses allow you to detect double crossovers and determine the order of three genes along a chromosome.
Genetic markers are identifiable loci (phenotypic, molecular, or DNA-based) used as reference points for mapping.
Mutations are the ultimate source of all new alleles. They introduce genetic variability.
Recombination (crossing over) shuffles existing alleles into new combinations, increasing the genetic diversity of offspring.
Together, mutation and recombination provide the raw material upon which natural selection acts.
"Dominant means common and recessive means rare." Dominance describes the allele's effect in the heterozygote, not its frequency in the population. A dominant allele can be rare (e.g., polydactyly).
"Incomplete dominance and codominance are the same thing." They are not. In incomplete dominance the heterozygote is a blend (red + white = pink). In codominance both phenotypes appear fully and simultaneously (red + white = red and white patches).
"If two genes are on the same chromosome, they always travel together." Only if they are very close. Crossing over can separate linked genes, and the farther apart they are, the more often this happens.
"A recombination frequency of 50% means the genes are linked." The opposite: 50% recombination is the maximum and is indistinguishable from independent assortment, meaning the genes are either on different chromosomes or so far apart on the same chromosome that a crossover almost always occurs between them.
⚠️ Be able to work through monohybrid, dihybrid, and test crosses with Punnett squares or the probability method and predict phenotype/genotype ratios.
⚠️ Distinguish incomplete dominance (1:2:1 phenotype ratio) from codominance (both alleles visible simultaneously) and from simple dominance (3:1).
⚠️ Know the ABO blood type system as an example of both multiple alleles and codominance.
⚠️ Be prepared to calculate recombination frequencies and convert them to map units.
⚠️ Understand why double crossovers lead to underestimation of map distance and how three-point crosses solve this.
⚠️ X-linked inheritance patterns are a favourite exam topic: predict outcomes for carrier females, affected males, and explain why fathers do not pass X-linked traits to sons.
True or False: Mendel's Second Law applies to genes on the same chromosome. Answer: False. Independent assortment applies to genes on different chromosomes. Genes on the same chromosome are linked.
Fill in the blank: In a test cross, the individual with the unknown genotype is crossed with a ______ individual. Answer: homozygous recessive.
True or False: In codominance, the heterozygote phenotype is intermediate between the two homozygotes. Answer: False. That describes incomplete dominance. In codominance, both alleles are fully and separately expressed.
Fill in the blank: A recombination frequency of 12% between two genes corresponds to ______ map units. Answer: 12.
True or False: A father can pass an X-linked recessive allele to his son. Answer: False. Fathers pass the Y chromosome to sons and the X chromosome to daughters.
Q: In a cross between two heterozygous parents (Aa x Aa) for a trait showing simple dominance, what are the expected genotype and phenotype ratios in the offspring?
A: Genotype ratio: 1 AA : 2 Aa : 1 aa. Phenotype ratio: 3 dominant : 1 recessive.
Q: Explain why X-linked recessive traits appear more frequently in males than in females.
A: Males have one X chromosome and one Y chromosome. A single recessive allele on the X is expressed because there is no second X to carry a dominant allele that could mask it. Females have two X chromosomes, so they would need two copies of the recessive allele (one on each X) to express the trait, which is much less likely.
Q: Two genes, A and B, show a recombination frequency of 8%. Genes B and C show a recombination frequency of 5%. Genes A and C show a recombination frequency of 13%. What is the gene order?
A: The gene order is A – B – C (or equivalently C – B – A). Since A-C distance (13 cM) equals A-B (8 cM) + B-C (5 cM), B is between A and C.
Q: How does incomplete dominance affect the phenotype ratio in an F2 cross compared to simple dominance?
A: In simple dominance, the F2 phenotype ratio is 3:1 because the heterozygote looks the same as the homozygous dominant. In incomplete dominance, the heterozygote has a distinct intermediate phenotype, so the phenotype ratio becomes 1:2:1, matching the genotype ratio.
Q: Describe Sutton's Chromosomal Theory of Inheritance and explain how it connects Mendel's laws to the physical behaviour of chromosomes.
A: Sutton proposed that genes are located on chromosomes. During meiosis I, homologous chromosomes (which carry the two alleles of each gene) separate, producing the segregation Mendel described. Because different pairs of homologous chromosomes orient independently on the metaphase I plate, genes on different chromosomes assort independently, fulfilling Mendel's second law.
The genetics covered here underpins the molecular biology that follows. Mendel described patterns; transcription and translation (Part 3 of these notes) explain the mechanism by which genotype becomes phenotype. Sickle cell anaemia, Huntington disease, and cystic fibrosis, covered in the clinical correlations section of Part 3, are all examples of Mendelian inheritance at the molecular level.
Gene linkage and mapping also connect back to the history block: Morgan's work with Drosophila (Part 1) first demonstrated sex linkage, and McClintock's cytological proof of crossing over gave the physical evidence for recombination.
Mendelian genetics, monohybrid cross, dihybrid cross, test cross, Punnett square, probability method, segregation, independent assortment, Mendel's First Law, Mendel's Second Law, Sutton chromosomal theory, incomplete dominance, codominance, multiple alleles, ABO blood type, polygenic inheritance, mitosis, meiosis, gene linkage, X-linked traits, sex-linked inheritance, crossing over, recombination frequency, genetic map, centimorgan, three-point cross, Janssen chiasmata, McClintock, genetic markers, UCF Molecular Biology I Exam 1