Mendelian inheritance Flashcards
Describe the characteristics of Mendelian inheritance, both autosomal and sex-linked.
Characteristics of Mendelian Inheritance
Mendelian inheritance refers to the pattern of inheritance of genetic traits as described by Gregor Mendel in the mid-1800s, based on his experiments with pea plants. Mendel identified that traits are inherited according to specific laws, which we now refer to as Mendel’s laws of inheritance. These laws apply to most traits governed by single genes located on chromosomes, and they describe how alleles (different forms of a gene) are inherited across generations.
Mendelian inheritance can be divided into two main categories based on where the genes are located on chromosomes:
Autosomal inheritance (genes located on autosomes, which are non-sex chromosomes)
Sex-linked inheritance (genes located on sex chromosomes, X or Y).
1. Autosomal Inheritance
Autosomal inheritance refers to the inheritance of traits controlled by genes located on the autosomes (chromosomes 1–22 in humans). Each individual has two copies of each autosomal gene—one from their mother and one from their father. Autosomal inheritance patterns can be classified as dominant or recessive.
Autosomal Dominant Inheritance
Dominant alleles are expressed in the presence of just one copy of the allele (heterozygous condition).
An individual with a heterozygous genotype (one dominant allele and one recessive allele) will express the dominant trait.
A homozygous dominant individual (two dominant alleles) will also express the dominant trait.
A recessive allele only expresses its associated trait when the individual is homozygous recessive (both alleles are recessive).
Key Characteristics:
Affected individuals typically have affected parents, but the disorder can also appear in the next generation if one parent is heterozygous.
Vertical transmission: The trait tends to appear in multiple generations of a family.
Both males and females are equally likely to inherit the gene, and the trait is equally transmitted by both parents.
Examples of autosomal dominant disorders:
Huntington’s disease: A neurodegenerative disorder.
Achondroplasia: A form of dwarfism.
Marfan syndrome: A connective tissue disorder.
Autosomal Recessive Inheritance
Recessive alleles require two copies (homozygous) to express the trait (i.e., both alleles must be recessive).
A person who is heterozygous for a recessive allele (i.e., a carrier) typically does not show the disorder but can pass on the allele to their offspring.
Key Characteristics:
A homozygous recessive individual must inherit one copy of the mutated gene from both parents to express the disease.
Carrier parents (heterozygous) typically do not show symptoms but can pass the recessive allele to their children.
Horizontal transmission: The trait often appears in siblings, not necessarily in parents or grandparents, and may skip generations.
The disorder may be more common in certain populations or ethnic groups due to genetic drift or consanguinity (marriage between relatives).
Examples of autosomal recessive disorders:
Cystic fibrosis: A disorder affecting the lungs and digestive system.
Sickle cell anemia: A blood disorder where red blood cells take on a sickle shape.
Tay-Sachs disease: A neurodegenerative disorder common among Ashkenazi Jews.
2. Sex-Linked Inheritance
Sex-linked inheritance refers to the inheritance of genes located on the sex chromosomes (X and Y). In humans, females have two X chromosomes (XX), and males have one X and one Y chromosome (XY). Since the X and Y chromosomes are not homologous, the inheritance patterns for X-linked and Y-linked traits differ.
X-linked Inheritance
X-linked dominant and X-linked recessive disorders are caused by mutations in genes located on the X chromosome.
Females have two X chromosomes, so they can be homozygous or heterozygous for X-linked traits.
Males have one X chromosome, so they will express an X-linked trait if they inherit the affected allele on their single X chromosome.
X-linked Dominant Inheritance
In X-linked dominant inheritance, a single copy of the dominant allele on the X chromosome is enough to express the trait.
Both males and females can be affected, but males are often more severely affected because they have only one X chromosome.
Key Characteristics:
Affected females can inherit the allele from either parent (because they have two X chromosomes), while affected males must inherit the allele from their mother (because they inherit their X chromosome from their mother).
Fathers cannot pass X-linked traits to their sons (since sons inherit the Y chromosome from their father), but they can pass them to daughters (who inherit the father’s X chromosome).
Examples of X-linked dominant disorders:
Fragile X syndrome: A genetic condition causing intellectual disability.
Rett syndrome: A neurodevelopmental disorder that affects mostly females.
X-linked Recessive Inheritance
In X-linked recessive inheritance, males who inherit an X-linked recessive allele will express the trait, because they have only one X chromosome.
Females need two copies of the recessive allele (one on each X chromosome) to express the disease. If they have only one affected allele, they will be carriers but typically won’t express the trait.
Key Characteristics:
Males are more likely to be affected because they only have one X chromosome. If they inherit the recessive allele, they will express the disorder.
Females are usually carriers if they have only one affected X chromosome, and they typically do not express the disease unless they inherit two copies of the mutated gene.
Affected males transmit the allele to all of their daughters (because daughters inherit the father’s X chromosome), but not to their sons (because sons inherit the Y chromosome).
Examples of X-linked recessive disorders:
Hemophilia A: A blood clotting disorder.
Duchenne muscular dystrophy: A progressive muscle weakness condition.
Color blindness: A condition affecting the ability to see certain colors.
Y-linked Inheritance
Y-linked inheritance refers to genes located on the Y chromosome, and these traits are passed only from father to son.
There are relatively few genes on the Y chromosome, and most of them are involved in male sex determination and spermatogenesis (the production of sperm).
Key Characteristics:
Traits passed on the Y chromosome will only be expressed in males, as females do not have a Y chromosome.
Examples of Y-linked inheritance:
Hypertrichosis pinnae: Excessive hair growth on the ears, which is caused by a mutation on the Y chromosome.
Construct and use human pedigrees to establish patterns of inheritance.
A pedigree is a family tree diagram that shows the occurrence and transmission of specific traits or genetic conditions across generations. Pedigrees are crucial tools in genetics and genetic counseling because they allow clinicians and geneticists to determine how a trait or genetic condition is inherited, whether it’s autosomal dominant, autosomal recessive, X-linked dominant, or X-linked recessive.
How to Construct a Pedigree
Start with the Proband: The individual from whom the pedigree begins is called the proband or index case. This is the person with the condition or trait that is being tracked.
Use Standard Symbols:
Squares represent males.
Circles represent females.
A filled shape (square or circle) indicates an individual who expresses the trait.
A half-filled shape indicates a carrier (heterozygous) for a recessive trait.
An empty shape indicates an unaffected individual.
Horizontal lines connecting a male and female represent marriage or union.
Vertical lines leading from a couple represent their children.
Include Generational Labels: Generations are numbered starting with the first generation (P) at the top and moving downward. The first generation is labeled as P (proband), the next as F1, then F2, and so on.
Add Information: For each individual, include information such as their phenotype (affected or unaffected), carrier status if relevant, and the mode of inheritance you’re trying to determine.
Key Steps in Using a Pedigree to Establish Patterns of Inheritance
Once a pedigree has been constructed, you can analyze it to determine the inheritance pattern. Below are the steps for identifying common inheritance patterns.
- Autosomal Dominant Inheritance
Key Characteristics:
A dominant allele requires only one copy of the gene to express the trait.
Both males and females are affected equally.
The condition typically appears in every generation (i.e., vertical transmission).
Affected individuals often have at least one affected parent.
If an affected person has a heterozygous genotype, there is a 50% chance of passing the gene to offspring.
Pedigree Analysis for Autosomal Dominant Inheritance:
If a trait is autosomal dominant, affected individuals will have at least one affected parent.
For a heterozygous parent, there is a 50% chance of passing the condition to each child.
Unaffected individuals do not carry the dominant allele and cannot pass the trait to their offspring.
Example: Huntington’s disease is an autosomal dominant condition. A pedigree might show that each affected person has at least one affected parent, and both males and females can be affected in every generation.
Pedigree Example (Autosomal Dominant):
scss
Copy code
P1 (affected) - P2 (unaffected)
|
F1 (affected) - F2 (affected)
2. Autosomal Recessive Inheritance
Key Characteristics:
Recessive alleles require two copies (homozygous) to express the trait.
The trait can skip generations (i.e., horizontal transmission).
Affected individuals typically have heterozygous carrier parents who are unaffected.
The trait is more likely to appear when parents are related (inbreeding increases the chance of inheriting two copies of a recessive allele).
Pedigree Analysis for Autosomal Recessive Inheritance:
Unaffected parents can have an affected child if both are carriers (heterozygous).
Typically, affected individuals do not have affected parents but will have siblings who are affected.
In a large family, the trait may appear in multiple siblings but not in parents or grandparents.
Example: Cystic fibrosis is an autosomal recessive condition. Parents who are carriers (heterozygous) may have an affected child if both pass on the mutated gene.
Pedigree Example (Autosomal Recessive):
scss
Copy code
P1 (carrier) - P2 (carrier)
|
F1 (affected)
3. X-linked Dominant Inheritance
Key Characteristics:
The gene causing the disorder is located on the X chromosome.
Females are affected if they inherit the dominant allele from either parent, whereas males are affected if they inherit the allele from their mother.
Males typically have more severe symptoms because they have only one X chromosome.
Affected fathers will pass the gene to all of their daughters, but none of their sons (since sons inherit the Y chromosome from their father).
Females can pass the condition to both sons and daughters.
Pedigree Analysis for X-linked Dominant Inheritance:
Affected fathers will have affected daughters (but not sons).
Affected mothers can pass the trait to both sons and daughters.
Females are often less severely affected than males.
Example: Rett syndrome is an example of an X-linked dominant disorder. Daughters of affected males will always inherit the condition, while sons will not.
Pedigree Example (X-linked Dominant):
scss
Copy code
P1 (affected female) - P2 (unaffected male)
|
F1 (affected male)
4. X-linked Recessive Inheritance
Key Characteristics:
The gene causing the disorder is located on the X chromosome.
Males are affected if they inherit one copy of the mutant gene (since they have only one X chromosome).
Females need two copies of the mutated gene (homozygous) to be affected. Typically, females are carriers if they inherit one affected allele.
Affected males pass the mutation to all of their daughters, but not to their sons.
Carrier females can pass the mutation to both sons and daughters.
Pedigree Analysis for X-linked Recessive Inheritance:
Affected males cannot pass the disorder to their sons, but they will pass it to all of their daughters, who will be carriers.
Carrier females have a 50% chance of passing the trait to their sons, and a 50% chance of passing the carrier status to their daughters.
Example: Hemophilia A is an X-linked recessive condition. Affected males will pass the trait to their daughters, but not their sons. Carrier females may pass the gene to their sons, causing hemophilia.
Pedigree Example (X-linked Recessive):
scss
Copy code
P1 (affected male) - P2 (carrier female)
|
F1 (female carrier) - F2 (affected male)
Example Pedigree Analyses
Example 1: Autosomal Dominant Trait
scss
Copy code
P1 (affected) — P2 (unaffected)
|
F1 (affected) — F2 (unaffected)
|
F3 (affected)
Inheritance pattern: This is an autosomal dominant inheritance pattern.
Explanation: An affected parent (P1) passes the gene to both sons and daughters. The trait appears in multiple generations (vertical transmission).
Example 2: Autosomal Recessive Trait
scss
Copy code
P1 (carrier) — P2 (carrier)
|
F1 (affected)
Inheritance pattern: This is an autosomal recessive inheritance pattern.
Explanation: Two carrier parents pass on one affected allele each, resulting in an affected child. The trait can skip generations.
Example 3: X-linked Recessive Trait
scss
Copy code
P1 (affected male) — P2 (unaffected female)
|
F1 (carrier female) — F2 (affected male)
Inheritance pattern: This is an X-linked recessive inheritance pattern.
Explanation: Affected males pass the trait to all daughters (who become carriers), but not to sons. A carrier female can pass the allele to both sons and daughters.
Conclusion
Pedigrees are powerful tools for identifying patterns of inheritance in families. By analyzing the inheritance patterns across generations, geneticists can determine whether a trait is autosomal dominant, autosomal recessive, X-linked dominant, or X-linked recessive. Understanding these patterns helps predict the likelihood of a genetic condition appearing in future generations and aids in genetic counseling.
Calculate genetic risk from pedigree structure.
Calculating genetic risk from a pedigree involves using the family history to estimate the probability of inheriting a genetic condition. This is particularly important in genetic counseling, where it helps predict the likelihood that an individual or their offspring will inherit or develop a genetic condition. The process involves identifying inheritance patterns (e.g., autosomal dominant, autosomal recessive, X-linked) and calculating probabilities based on those patterns.
Steps for Calculating Genetic Risk from a Pedigree
Identify the Inheritance Pattern:
Autosomal Dominant: Affected individuals usually have an affected parent. A single copy of the mutated allele is sufficient to express the trait.
Autosomal Recessive: Both parents are carriers (heterozygous) or affected (homozygous) for the disease allele. Two copies of the mutated gene are needed to express the trait.
X-linked Dominant: The gene causing the condition is located on the X chromosome, and one copy of the mutated allele is sufficient for females to express the condition. Males are more severely affected.
X-linked Recessive: Males are affected by the condition if they inherit one copy of the mutated allele on their X chromosome. Females need two copies of the allele to be affected.
Determine the Genotypes of Family Members: Use the pedigree to infer the genotypes of individuals. Based on their phenotype (affected or unaffected), you can assign potential genotypes:
Autosomal Dominant: If an individual is affected, they must carry at least one dominant allele (heterozygous or homozygous dominant).
Autosomal Recessive: If an individual is unaffected but has an affected child, they are likely a carrier (heterozygous).
X-linked Dominant: Affected females can be either heterozygous or homozygous for the mutation. Affected males must have the mutation on their single X chromosome.
X-linked Recessive: Males with the condition have the mutation on their X chromosome. Females with the condition must have two affected alleles.
Calculate the Probability of Inheritance: Based on the inheritance pattern and the genotypes of the parents, you can calculate the probability that offspring will inherit the genetic condition. Probabilities are typically expressed as a percentage or fraction.
Example 1: Autosomal Dominant Inheritance
Let’s consider a family where a father (P1) is affected by an autosomal dominant disorder and the mother (P2) is unaffected. They have a child (F1), and we need to calculate the risk of the child inheriting the disorder.
Father’s genotype: Since the father is affected and the disorder is dominant, his genotype could be either AA (homozygous dominant) or Aa (heterozygous).
Mother’s genotype: Since the mother is unaffected, her genotype is most likely aa (homozygous recessive).
Let’s calculate the risk of the child being affected:
If the father is AA (homozygous dominant), then all offspring (regardless of sex) will inherit one A allele and be affected.
If the father is Aa (heterozygous), there is a 50% chance of passing on the A allele and 50% chance of passing on the a allele.
Risk Calculation for Child’s Inheritance:
Father (Aa) × Mother (aa):
50% chance of the child inheriting A (affected).
50% chance of the child inheriting a (unaffected).
So, there is a 50% chance that the child will inherit the condition, whether the child is male or female.
If the father is AA, then the risk is 100% for the child to inherit the condition.
Example 2: Autosomal Recessive Inheritance
Let’s now consider a family with parents who are both carriers for an autosomal recessive disorder (heterozygous, Aa), and we need to calculate the risk of their child being affected.
Father’s genotype: Aa (carrier).
Mother’s genotype: Aa (carrier).
The possible combinations for their child’s genotype are:
AA (unaffected): 25% chance.
Aa (carrier): 50% chance.
aa (affected): 25% chance.
Risk Calculation for Child’s Inheritance:
The probability that the child will be affected (aa) is 25%.
The probability that the child will be a carrier (Aa) is 50%.
The probability that the child will be unaffected and not a carrier (AA) is 25%.
Therefore, the risk of the child being affected is 25%.
Example 3: X-linked Recessive Inheritance
Consider a pedigree where the father (P1) has an X-linked recessive condition, and the mother (P2) is unaffected. The couple has a son, and we need to calculate the risk of the son inheriting the disorder.
Father’s genotype: Since the father is affected, his genotype is X
𝐴
A
Y (where X
𝐴
A
carries the mutation).
Mother’s genotype: Since the mother is unaffected, her genotype is likely X
𝐴
A
X
𝐴
A
(homozygous unaffected).
Risk Calculation for Son’s Inheritance:
The father passes his Y chromosome to his son, so he does not pass the X-linked mutation to the son.
The mother passes one of her X chromosomes to the son. Since the mother is X
𝐴
A
X
𝐴
A
(unaffected), the son will inherit the unaffected X
𝐴
A
chromosome from her.
Thus, the son has a 0% chance of inheriting the condition because he does not inherit the mutated X chromosome from his mother or father.
Example 4: X-linked Dominant Inheritance
Consider a pedigree where the mother (P1) has an X-linked dominant disorder, and the father (P2) is unaffected. They have a daughter, and we need to calculate the risk of the daughter inheriting the disorder.
Mother’s genotype: Since the mother is affected by an X-linked dominant disorder, she could be X
𝐴
A
X
𝐴
A
(homozygous) or X
𝐴
A
X
𝑎
a
(heterozygous).
Father’s genotype: The father is unaffected, so his genotype is X
𝑎
a
Y (normal).
Risk Calculation for Daughter’s Inheritance:
If the mother is X
𝐴
A
X
𝐴
A
(homozygous), then she will pass the X
𝐴
A
chromosome to all of her daughters. Thus, the daughter will definitely inherit the condition.
If the mother is X
𝐴
A
X
𝑎
a
(heterozygous), there is a 50% chance that the daughter will inherit the X
𝐴
A
chromosome (and thus be affected) and a 50% chance of inheriting the X
𝑎
a
chromosome (and being unaffected).
Thus, if the mother is heterozygous (X
𝐴
A
X
𝑎
a
), the risk for the daughter to inherit the condition is 50%.
Key Points to Remember When Calculating Genetic Risk:
Autosomal dominant inheritance: Affected individual (heterozygous or homozygous) has a 50% chance of passing the trait to each child.
Autosomal recessive inheritance: Two carrier parents have a 25% chance of having an affected child, a 50% chance of having a carrier child, and a 25% chance of having an unaffected child.
X-linked recessive inheritance: Males with the condition pass the allele to all daughters but not to sons. Carrier females have a 50% chance of passing the gene to each son and 50% chance of passing carrier status to each daughter.
X-linked dominant inheritance: Affected females (whether homozygous or heterozygous) pass the condition to both sons and daughters. Affected males pass the condition only to daughters.
Conclusion
By analyzing pedigrees and considering the inheritance pattern, you can calculate the probability of offspring inheriting genetic conditions. This is particularly useful for genetic counseling to inform families about the potential risks of genetic disorders being passed to future generations.
