Mendel and Genetic Inheritance
Principles of Trait Inheritance
The question is: What principles account for the passing of traits from parents to offspring?
The "blending" hypothesis:
Hereditary material from the two parents blends together (like blue and yellow paint blend to make green).
Over many generations, this would result in a uniform population.
The "particulate" hypothesis:
Discrete heritable units (genes) are passed down.
Mendel and the Gene Idea
Mendel: The Father of Genetics
Mendelian Genetics
Name derives from Austrian monk, Gregor Mendel.
Mendel documented a particulate mechanism.
He controlled the mating of pea plants.
Observed distinct patterns of inheritance.
Developed rules that applied to the manner in which genetic material is passed from generation to generation.
Terminology
Character (or characteristic): Heritable features that vary among individuals.
Trait: Each variant of a character.
Example: Mendel worked on pea plants that had different flower colors (white & purple).
Peas have many different characters with multiple traits that can be studied.
Flower color is the character.
Purple and white are the traits.
Mendel's Scientific Approach
Mendel used a scientific approach to identify the laws of inheritance.
Mendel only studied characters that varied in an either-or manner.
Peas have a short generation time and produce many offspring.
Mendel started with plants that had self-pollinated over many generations and only gave the same trait – true-breeding.
Mendel could strictly control mating between plants.
Note: stamen = sperm producing part of plant. Carpel = egg producing part of plant.
Using this method, Mendel crossed a true-breeding purple-flowered plant with a true-breeding white-flowered plant.
The offspring of the first cross were all purple.
The question is: Is the white flower trait still there but hidden, or has it been destroyed?
Mendel allowed the offspring to self-pollinate, and the white trait reappeared in the offspring.
Mendel’s original cross:
Parental generation.
First filial generation.
Second filial generation.
This is approximately a 3:1 ratio!!
Mendel repeated this experiment, studying other characters in peas and always observed a 3:1 ratio in the F2 generation.
Mendel used the results of these experiments to make a model of inheritance.
He referred to "heritable factors," which we now call genes.
Mendel's Model of Inheritance
Concept 1: Alternate versions of genes account for variations in inherited characters.
We refer to these alternate versions as alleles.
The gene for flower color in peas has two alleles: purple & white.
Concept 2: For each character, an organism inherits two copies of the gene, one from each parent.
Mendel made this deduction without knowing about the role of chromosomes!
You can have identical alleles on both chromosomes – true-breeding.
You can have a different allele on each chromosome – hybrid.
Concept 3: If an organism has two different alleles for a gene, then one determines the organism’s appearance & the other has no noticeable effect.
The allele that determines appearance is referred to as dominant, and the masked allele is referred to as recessive.
Concept 4: The Law of Segregation
The two alleles for a heritable character separate (segregate) during gamete formation and end up in different gametes.
Homologous chromosomes separate during meiosis I.
Each homologue will have one allele.
Genetic Vocabulary
Homozygous: An organism with two identical alleles for a character.
Heterozygous: An organism that has two different alleles for a gene.
Because of the different effects of dominant and recessive alleles, an organism’s traits do not always reveal its genetic composition.
Therefore, we distinguish between an organism’s:
Phenotype: physical appearance.
Genotype: genetic makeup.
It is possible to have the same phenotype but a different genotype.
Punnett Square
Does Mendel’s segregation model account for the 3:1 ratio he observed?
Possible combinations of sperm and egg can be shown using a Punnett square.
A diagram for predicting the results of a genetic cross between individuals of known genetic makeup.
(Reginald Punnett worked with William Bateson on genetics research at Cambridge. William Bateson brought Mendel's laws to the attention of English scientists.)
In a Punnett square, the genes are represented by letters.
Dominant alleles are represented with a capital letter.
Recessive alleles are represented with a lower case letter.
Remember that each allele will be located on one of the pair of homologous chromosomes.
Testcross
How to tell the genotype of an individual with the dominant phenotype?
Do a testcross: breed the mystery individual with a homozygous recessive individual.
If any offspring display the recessive phenotype, the mystery parent must be heterozygous.
Genetics Problem
Question 2. In a particular plant, leaf color is controlled by gene locus D. Plants with at least one allele D have dark green leaves, and plants with the homozygous recessive dd genotype have light green leaves.
A true-breeding dark-leaved plant is crossed with a light-leaved one, and the F1 offspring is allowed to self-pollinate. The predicted outcome of the F2 is diagrammed in the Punnett square below, where 1, 2, 3, and 4 represent the genotypes corresponding to each box within the square.
Gametes : D d
F1: Dd
F2: Dd X Dd
Which of the boxes marked 1-4 correspond to plants with dark leaves?
D. 1, 2 and 3
Which of the boxes correspond to plants with a heterozygous genotype?
C. 2 and 3
Which of the plants will be true-breeding?
A. 1 and 4
Dihybrid Cross
What about if we look at two different characteristics at the same time?
Mendel derived the law of segregation by following a single character.
E.g. Flower color.
The F1 offspring produced in the cross of true-breeding parents were monohybrids, heterozygous for one character (Pp).
A cross between such heterozygotes is called a monohybrid cross.
But what about if we look at two characters at the same time?
Eg pea color (green or yellow) & pea shape (round or wrinkled)?
Will the two characters be inherited together or separately?
The dihybrid cross: Mendel followed two characters at the same time.
Will peas only ever be round and yellow or green and wrinkled (characters inherited together), or will we see all possible combinations: yellow & round; yellow & wrinkled; green & round; green & wrinkled (characters inherited independently of each other)?
Parents are true breeding for both characters.
Do alleles for one character segregate into gametes dependently or independently of the alleles for a different character?
Not only did Mendel observe all combinations of the characters, he also observed them in a particular ratio:
9 yellow & round: 3 green & round: 3 yellow & wrinkled: 1 green wrinkled.
Results support independent assortment!
Mendel’s Second Law: The Law of Independent Assortment
Each pair of alleles segregates independently of each other pair of alleles during gamete formation.
*There are some exceptions to this rule which we will discuss in the next lecture.
*QuestionA sexually reproducing animal has two unlinked genes, one for head shape (H) and one for tail length (T). It’s genotype is HhTt. Which of the following genotypes is possible in a gamete from this organism?
C. HT
Laws of Probability Govern Mendelian Inheritance
Mendel’s laws reflect the rules of probability.
When tossing a coin, the outcome of one toss has no impact on the outcome of the next toss.
In the same way, the alleles of one gene segregate into gametes independently of another gene’s alleles.
Multiplication Rule – Monohybrid Crosses
Multiplication rule: the probability that two or more independent events will occur together is the product of their individual probabilities.
Segregation in a heterozygous plant is like flipping a coin.
Addition Rule – Monohybrid Crosses
The rule of addition states that the probability that any one of two or more exclusive events will occur is calculated by adding together their individual probabilities.
Can be used to figure out the probability that an F2 plant from a monohybrid cross will be heterozygous rather than homozygous.
Genetics Problems
*Question
Brown eyes in horses (B) is dominant to blue eyes (b). Dark hair (H) is dominant to light hair (h). What fraction of the progeny of the cross BbHh × BBhh will have brown eyes and light hair?
E. 1/2
*Question
In certain plants, tall is dominant to short. If a heterozygous plant is crossed with a homozygous short plant, what is the probability that the offspring will be short?
C. 1/2
*Practice Question
Two true-breeding stocks of pea plants are crossed. One parent has red, axial flowers, and the other has white, terminal flowers; all F1 individuals have red, axial flowers. The genes for flower color and location assort independently. If 1,000 F2 offspring resulted from the cross, approximately how many of them would you expect to have red, terminal flowers?
B. 190
Solving Complex Genetic Problems
We can apply the laws of probability to predict the outcome of crosses involving multiple characters.
A dihybrid cross is equivalent to two or more independent monohybrid crosses occurring simultaneously.
In calculating the chances for various genotypes, each character (gene) is considered separately, and then the individual probabilities are multiplied together.
*QuestionIn a cross AaBbCc × AaBbCc, what is the probability of producing the genotype AABBCC?
B. 1/8
*Question
Given the parents AABBCc × AabbCc, assume simple dominance for each trait and independent assortment. What proportion of the progeny will be expected to phenotypically resemble the first parent with genotype AABBCc?
B. ¾
Human Traits and Patterns of Inheritance
Humans are not good subjects for genetic research:
Long generation time.
Few offspring.
Breeding experiments are unacceptable.
However, basic Mendelian genetics endures as the foundation of human genetics.
How do we track Mendelian traits in humans?
Pedigree Analysis
A pedigree is a family tree that describes the interrelationships of parents and children across generations.
Inheritance patterns of particular traits can be traced and described using pedigrees.
Pedigree analysis of the same family through three generations looking at two different characters:
Widow’s peak present or absent.
Inability to taste PTC.
Tip for analysis: 3rd generation, 2nd born daughter lacks widow’s peak even though both parents have it. Trait must be dominant.
Tip for analysis: 3rd generation, 1st born has the trait (unable to taste). Trait must be recessive.
Pedigrees can also be used to make predictions about future offspring.
Use multiplication and addition rules to predict the probability of specific phenotypes.
Rule of addition: the probability that any one of two or more exclusive events will occur is calculated by adding together their individual probabilities.
Multiplication rule: the probability that two or more independent events will occur together is the product of their individual probabilities.
What’s the probability the third child has a widow’s peak?
We used the pedigree to determine the genotype of the parents.
Then we can use a Punnett square to work out the probability.
What's the probability that this same child cannot taste PTC?
So, what the probability that this child will have a widow’s peak and attached can’t taste PTC?
Assuming the genes are not linked, i.e., they are on different chromosomes, and they assort independently in this dihybrid cross…
Then,
i.e., the multiplication rule because we are testing the probability of two or more independent events occurring together.
*Question
The pedigree below shows inheritance of a genetic disorder in humans. Is this disorder caused by a dominant or recessive allele? What genotypes are possible for each of the individuals?
Recessively Inherited Disorders
Many genetic disorders are inherited in a recessive manner.
Recessively inherited disorders show up only in individuals homozygous for the allele.
Carriers are heterozygous individuals who carry the recessive allele but are phenotypically normal.
Eg Albinism, Hemophilia.
Albinism: a recessive trait.
What is the probability that the sister with normal coloration is a carrier?
Matings between close relatives increase the likelihood of producing homozygous recessive offspring.
If a recessive allele that causes a disease is rare, then the chance of two carriers meeting and mating is low.
Consanguineous matings (i.e., matings between close relatives) increase the chance of mating between two carriers of the same rare allele.
Many societies and cultures have laws or taboos against marriages between close relatives…
Frequency of alleles in a population.
Dominant alleles are not necessarily more common in populations than recessive alleles.
For example, one baby out of 1345 in Australia is born with extra fingers or toes (polydactyly).
In some cases, the allele is dominant to the allele for the more common trait of five digits per appendage.
The recessive allele is far more prevalent than the population’s dominant allele.
What determines the frequency of genes in a population?
Why do recessive alleles that cause disease remain in the gene pool at all?
Some genes that cause disease in homozygous recessive individuals can offer a selective advantage to the heterozygote.
Cystic fibrosis:
Mutation affects chloride channels.
Affects one out of every 2,500 people of European descent (1/25 are carriers).
Heterozygote carriers are protected against cholera (killed millions in 19th century Europe).
Sickle cell trait and thalassemia:
Mutations that affect hemoglobin, therefore O2 transport.
Sickle cell: People of African descent - 1/10 carriers.
Thalassemia: People of Southern European (60% carriers) or South East Asian descent (40 % carriers).
Heterozygotes are protected against malaria, “the most deadly disease to affect mankind.”
Dominantly Inherited Disorders
Some human disorders (?) are caused by dominant alleles.
E.g., Achondroplasia is a form of dwarfism caused by a rare, dominant allele.
*QuestionA man has extra digits (six fingers on each hand and six toes on each foot). His wife and their daughter have a normal number of digits. Having extra digits is a dominant trait. The couple's second child has extra digits. What is the probability that their next (third) child will have extra digits?
1/2
Dominant disorders that cause disease are usually removed from the gene pool quickly.
Dominant alleles that cause a lethal disease are rare and arise by mutation.
Individuals don’t live long enough to reproduce and pass on affected alleles.
Exception: Huntington’s disease.
A lethal degenerative disease of the nervous system.
The disease has no obvious phenotypic effects until the individual is about 35-40 years of age - reproduction has already occurred.
Multifactorial Disorders
Most diseases, such as heart disease and cancer, have both genetic and environmental components.
Little is understood about the genetic contribution to most multifactorial diseases.
Genetic Testing and Counselling
Genetic counselors can provide information to prospective parents concerned about a family history for a specific disease.
Counseling based on Mendelian genetics, probability rules & genetic tests.
Using family histories, genetic counselors help couples determine the odds that their children will have genetic disorders.
Fetal cells testing can be obtained for testing via amniocentesis or chorionic villus sampling.
15- 16 weeks the liquid that bathes the fetus is removed and tested
a sample of the placenta is removed and tested 8-10 weeks
Both methods slightly increase the chance of miscarriage
Maternal & Newborn screening
Some screening can now be done by taking maternal blood samples eg sex etc
less risk to the pregnancy
Slightly higher chance of false positive/inaccurate result
Some genetic disorders can be detected at birth by simple tests that are now routinely performed in most hospitals in Australia.
E.g., phenylketonuria.
Can’t metabolize phenylalanine, and accumulation causes mental retardation.
Can advise him?
Why is he suspicious?
He is working on the premise that eye color is determined by one gene with two alleles:
Brown = dominant, blue = recessive.
Both he and blue-eyed wife must be homozygous recessive.