Mendelian Genetics Overview

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Questions and Answers

What can cause AR disease to appear as a single case in families?

Demonstration of a full defect

Multiple affected siblings

High parental age

Small family size (correct)

What does genetic heterogeneity refer to?

Similar phenotypes arising from the same mutation

The same mutation causing varying severities

Identical mutations in different locations

Different genetic defects leading to similar clinical phenotypes (correct)

What is a common issue in pedigree analysis?

De novo mutations affecting all individuals

Deciphering allelic heterogeneity

Accurate representation of relatives (correct)

High rates of consanguinity

What examples illustrate allelic heterogeneity?

Different mutant versions of the same gene causing varying conditions Signup and view all the answers

What genetic defect leads to phenylketonuria (PKU)?

Major defect in the PAH gene Signup and view all the answers

What is the phenotype ratio of offspring from a heterozygote cross Rr x Rr?

3:1 Signup and view all the answers

In an autosomal dominant inheritance pattern, how many copies of the allele are needed to express the trait?

At least one Signup and view all the answers

What term describes the effect when a mutation in one copy of a gene results in a disease phenotype due to reduced gene product?

Haploinsufficiency Signup and view all the answers

In pedigree analysis, how are multiple siblings typically arranged?

By birth order Signup and view all the answers

Which of the following is an example of a gain of function mutation?

Achondroplasia Signup and view all the answers

What is the typical allele frequency in autosomal dominant diseases?

Low Signup and view all the answers

Which phenomenon occurs when an abnormal protein produced by a mutation interferes with the normal allele's function?

Dominant Negative Effect Signup and view all the answers

What is the genotype ratio observed in the offspring during a heterozygous cross Rr x Rr?

1:2:1 Signup and view all the answers

What is the total number of chromosomes in a diploid human cell?

46 Signup and view all the answers

Which term describes different versions of a gene?

Alleles Signup and view all the answers

What defines an individual as a homozygote?

Having two identical alleles for a gene Signup and view all the answers

What does genetic heterogeneity refer to?

Same disease phenotype caused by mutations in different genes Signup and view all the answers

Which genotype indicates a heterozygous condition?

Aa Signup and view all the answers

What characterizes autosomal recessive inheritance?

Both copies of the gene must be mutated to express the phenotype Signup and view all the answers

Which of the following is NOT a characteristic of a phenotype?

It strictly requires environmental factors Signup and view all the answers

How many pairs of homologous autosomes do humans possess?

22 Signup and view all the answers

What is eliminated from the bloodstream in familial hypercholesterolemia?

LDL cholesterol Signup and view all the answers

In autosomal dominant inheritance, what is the expected probability that an offspring will be affected if one parent is affected?

50% Signup and view all the answers

Which condition is characterized by abnormal collagen leading to bone fragility?

Osteogenesis imperfecta Signup and view all the answers

What does reduced penetrance refer to in genetics?

The proportion of individuals expressing a phenotype Signup and view all the answers

What inheritance pattern is observed in cystic fibrosis?

Autosomal recessive Signup and view all the answers

Which of the following genetic conditions displays a vertical pattern in a pedigree chart?

Huntington's disease Signup and view all the answers

What is the genotype of an affected individual with an autosomal recessive condition?

aa Signup and view all the answers

What ratio results from a cross between two carriers of an autosomal recessive trait?

1:2:1 Signup and view all the answers

Which of these diseases is an example of reduced ability to grow due to a loss of a tumor suppressor gene?

Neurofibromatosis Signup and view all the answers

What describes the phenotype of individuals in a horizontal inheritance pattern?

Occurs only in siblings Signup and view all the answers

What do you call the genetic makeup of an organism?

Genotype Signup and view all the answers

Which of the following represents the conditions of a recessive trait's manifestation?

aa Signup and view all the answers

What describes a situation where multiple genetic defects can lead to the same phenotype?

Locus heterogeneity Signup and view all the answers

How many sets of chromosomes do diploid individuals have?

2 sets Signup and view all the answers

Which of the following is a valid example of genetic polymorphism?

Variations in blood types Signup and view all the answers

What principle explains that a change in one allele can sometimes lead to a disease phenotype without a complete loss of function?

Dominant negative effect Signup and view all the answers

Which genotype is classified as a homozygote?

AA Signup and view all the answers

Which of the following best describes how genotypes influence phenotypes?

Genotype largely determines phenotype through its interaction with the environment Signup and view all the answers

Which statement best describes haploinsufficiency?

It results from having only one working copy of a gene when more than 50% is needed. Signup and view all the answers

What is the expected phenotype ratio from a cross of two heterozygous peas?

3:1 Signup and view all the answers

Which inheritance pattern requires only one affected allele in the phenotype expression?

Autosomal dominant Signup and view all the answers

Which of the following is NOT a result of a dominant negative effect?

Enhanced function of the normal gene product Signup and view all the answers

In an ADHD inherited via X-linked dominant trait, how is inheritance typically observed in pedigrees?

Both males and females inherit from affected parents. Signup and view all the answers

What commonly characterizes autosomal recessive inheritance?

Affected individuals normally appear in the offspring of unaffected parents. Signup and view all the answers

Which characteristic is associated with a gain of function mutation?

Increased activity of a mutant protein. Signup and view all the answers

In pedigree analysis, how is the proband typically indicated?

An asterisk. Signup and view all the answers

What challenge does genetic heterogeneity pose in understanding genetic diseases?

It results in identical clinical phenotypes from different genetic defects. Signup and view all the answers

Which situation is likely to result in difficulty during pedigree analysis?

Uncertain parentage of individuals in the lineage. Signup and view all the answers

What characterizes allelic heterogeneity in genetic conditions?

Multiple mutations in a single gene resulting in various phenotypic expressions. Signup and view all the answers

What is a common consequence of reduced penetrance in genetic diseases?

Some individuals with the mutation may not express the associated disease. Signup and view all the answers

What typical feature might indicate a case of autosomal recessive (AR) disease in a family?

Multiple affected siblings within a large family structure. Signup and view all the answers

What characterizes the inheritance pattern seen in autosomal dominant disorders?

Both sexes have equal probability of being affected. Signup and view all the answers

Which of the following is an autosomal recessive condition?

Sickle-cell anemia Signup and view all the answers

What describes the expected genotype ratio from a cross between two carriers of an autosomal recessive trait?

1:2:1 Signup and view all the answers

Which of the following disorders is linked to a mutant protein that damages neurons?

Huntington's disease Signup and view all the answers

Which statement is true regarding reduced penetrance?

It refers to the proportion of individuals expressing the phenotype with a given genotype. Signup and view all the answers

What is the expected phenotype ratio for offspring when a carrier mates with a non-carrier for an autosomal recessive trait?

1 affected: 1 normal Signup and view all the answers

What does variable expressivity in genetics refer to?

Differences in the severity or nature of the phenotype among individuals with the same genotype. Signup and view all the answers

In a typical autosomal dominant mating scenario represented by Aa + aa, what is the probability of the offspring being affected?

50% Signup and view all the answers

Which of the following conditions frequently exhibits a 'horizontal' pattern in pedigree analysis?

Cystic fibrosis Signup and view all the answers

What genetic factor allows for the development of colorectal tumors in familial adenomatous polyposis?

Damage to the APC protein Signup and view all the answers

Which factor could lead to AR disease being perceived as a unique occurrence in families with small sizes?

Parental consanguinity Signup and view all the answers

In pedigree analysis, which aspect can complicate the identification of accurate genetic relationships?

Uncertain parentage among individuals Signup and view all the answers

What is the major complication arising from genetic heterogeneity in clinical phenotypes?

Different mutations causing similar clinical presentations Signup and view all the answers

Which of these best illustrates the concept of allelic heterogeneity?

Variations in the same gene leading to differences in enzyme activity Signup and view all the answers

Which statement most accurately describes a challenge that can arise from reduced penetrance in genetic diseases?

Affected individuals may appear phenotypically normal despite having a mutation. Signup and view all the answers

What is the expected phenotype ratio for offspring produced from a cross between two heterozygous parents (Rr x Rr)?

3:1 Signup and view all the answers

Which condition is most likely to occur due to a gain of function mutation?

Achondroplasia Signup and view all the answers

In a pedigree analysis, which symbol typically represents an affected male?

Square Signup and view all the answers

Which term describes the phenomenon where a mutation produces an abnormal protein that hampers the normal allele's function?

Dominant negative effect Signup and view all the answers

How does haploinsufficiency lead to a disease phenotype?

Loss of more than 50% functionality of a protein Signup and view all the answers

In autosomal dominant inheritance, which statement accurately represents the likelihood of homozygotes surviving to reproductive age?

They frequently die before reproductive age. Signup and view all the answers

Which protein is commonly affected in familial hypercholesterolemia?

LDL receptor Signup and view all the answers

What distinguishes locus heterogeneity from allelic heterogeneity in genetic conditions?

Allelic heterogeneity occurs when multiple mutations appear in the same gene. Signup and view all the answers

Which of the following patterns is typical for diseases caused by autosomal recessive conditions?

Horizontal pattern in pedigree charts Signup and view all the answers

Which of the following best describes the relationship between genotypes and phenotypes?

Phenotypes reflect the interaction of genotypes with environmental factors. Signup and view all the answers

In a diploid organism, how many alleles exist for a single gene in the context of genetic polymorphism?

Up to two alleles in each individual, but more can exist in the population. Signup and view all the answers

What is the significance of having multiple alleles for a gene in a population?

It contributes to genetic diversity and potential adaptability. Signup and view all the answers

Which of the following statements about autosomal recessive inheritance is true?

Affected individuals must inherit two copies of the recessive allele. Signup and view all the answers

What characterizes autosomal dominant inheritance compared to autosomal recessive inheritance?

Individuals with the dominant trait can appear in every generation. Signup and view all the answers

Which scenario illustrates the concept of reduced penetrance in a genetic condition?

An affected individual showing no symptoms despite having the allele. Signup and view all the answers

How are genetic heterogeneity and its implications important for understanding genetic disorders?

It allows for the recognition that multiple mutations can lead to the same phenotype. Signup and view all the answers

Which statement accurately describes the inheritance pattern of Huntington's disease?

It exhibits a vertical pattern in pedigree analysis. Signup and view all the answers

In which of the following conditions does the function of a protein become detrimental to the cell?

Huntington's disease Signup and view all the answers

Which of the following statements regarding reduced penetrance is true?

It implies that some individuals with the genotype do not show the phenotype. Signup and view all the answers

Which disease is characterized by a vertical pattern in pedigree analysis due to its autosomal dominant inheritance?

Neurofibromatosis Signup and view all the answers

What is the expected genetic outcome when two carriers of an autosomal recessive disorder mate?

¼ affected, ½ carrier, ¼ normal Signup and view all the answers

Which of the following factors does NOT affect the expressivity of a genetic trait?

Sporadic mutations Signup and view all the answers

In the context of familial adenomatous polyposis, what specific genetic event commonly leads to cancer?

Loss of heterozygosity Signup and view all the answers

Which combination represents the most common mating type in autosomal dominant disorders?

Aa x aa Signup and view all the answers

Which of the following is an example of a condition associated with abnormal collagen resulting in bone issues?

Osteogenesis imperfecta Signup and view all the answers

Which of the following patterns is typical for autosomal recessive disorders in pedigree analysis?

Horizontal inheritance Signup and view all the answers

Study Notes

Mendelian Genetics

Genome: all genetic material in an organism, approximately 3 billion base pairs (bp)
Genome is organized into chromosomes: individual DNA molecules
Humans have 22 pairs of autosomes and 1 pair of sex chromosomes
Diploid: 2 sets of chromosomes (n=46), Haploid: 1 set of chromosomes (n=23)

Alleles

Most cells are diploid containing two homologous copies of each chromosome (one maternal and one paternal)
Each gene has two copies, one on each chromosome
Each gene copy is an allele
Alleles can vary in DNA sequence; these variations are called genetic polymorphisms

Genotypes

Genotype: genetic makeup
Phenotype: physical and/or biochemical characteristics of an organism based on the genotype
Phenotype is largely determined by genotype
Dominant allele: determines phenotype even when paired with a recessive allele
Recessive allele: only determines phenotype when paired with another recessive allele

Simple Mendelian Inheritance

Traits can be dominant (eg. in peas, round shape is dominant) or recessive (eg. wrinkled shape is recessive)
Heterozygous: two different alleles
Homozygous: two identical alleles

Mendelian Inheritance Patterns

Autosomal dominant (AD)
Autosomal recessive (AR)
Y-linked
X-linked dominant
X-linked recessive
Mitochondrial

Pedigree Analysis

Used to identify inheritance patterns in families
Proband: individual who first brings a family to the attention of a geneticist

Autosomal Dominant Inheritance

Expressed in both homozygotes (AA) and heterozygotes (Aa)
Most cases of AD disease are heterozygous because homozygotes may not survive to reproduction age
Allele frequencies in AD are typically low

How Single Gene Mutations Cause Disease in AD

Haploinsufficiency: Reduced gene product leads to disease; normal physiology requires >50% of a gene product
Dominant Negative Effect: Mutant protein interferes with the function of the normal allele
Gain of Function: Mutant protein functions are enhanced
Loss of Heterozygosity: Inherited mutation and random loss of the normal allele can lead to cancer

Examples of AD Inheritance

Familial hypercholesterolaemia: Low LDL cholesterol removal
Huntington's disease: Neuron damage due to mutant huntingtin protein
Osteogenesis imperfecta: Fragile bones due to abnormal collagen
Neurofibromatosis: Uncontrolled cell growth due to loss of neurofibromin protein
Familial adenomatous polyposis: Development of colorectal tumours due to damage to APC protein

AD Pedigree Characteristics

Vertical pattern: phenotype seen in every generation
Affected individuals have an affected parent
Both sexes have equal probability of being affected
Approximately 50% of offspring from an affected parent are affected

Most Common AD Mating Type

Aa + aa

Apparent Exceptions to AD Inheritance Pattern

Mutations: Sporadic cases due to new mutations
Variable Expressivity: Different degrees of phenotype severity in individuals with the same genotype
Reduced Penetrance: Not every individual with the genotype exhibits the phenotype

Autosomal Recessive Inheritance

Expressed only in homozygotes (aa)
Heterozygotes are carriers and are usually phenotypically normal
AR diseases are more common than AD; carriers are not at a selective disadvantage
AR diseases can become widespread even if affected individuals don't reproduce

AR Pedigree Characteristics

Horizontal pattern: Affected individuals are in a single sib-ship and disease doesn't occur in multiple generations
Both sexes affected with equal probability
When two carriers mate: 25% affected, 50% carriers, 25% normal

Examples of Autosomal Recessive Inheritance

Cystic fibrosis
Phenylketonuria
Albinism
Sickle-cell anaemia
α and β thallassaemia

Most Common AR Mating Type

Carrier x Carrier: Aa x Aa

Less Common AR Mating Types

Carrier x Affected: Aa x aa
Normal x Affected: AA x aa

General Problems in Pedigree Analysis

Uncertain parentage
Small family size
Difficulty obtaining accurate information about relatives
De novo mutations
Reduced penetrance/variable expressivity
Genetic heterogeneity

Genetic Heterogeneity

Different genetic defects can produce similar clinical phenotypes:
Allelic heterogeneity: Different mutations in the same gene
Locus heterogeneity: Mutations in different genes, often affecting complex pathways

Allelic Heterogeneity: Example: Phenylketonuria (PKU)

PKU involves a build-up of phenylalanine and ketones that can lead to mental retardation
Different mutations in the PAH gene can lead to different levels of enzyme activity and various severities of PKU.

### Genetics Basics

Genome is the complete set of genetic material, consisting of 3 billion base pairs
Human genome organized into chromosomes: 22 pairs of autosomes and 1 pair of sex chromosomes
Diploid cells contain 2 sets of chromosomes (n=46), haploid cells have 1 set (n=23)
Most cells are diploid, containing two homologous copies of each chromosome, one from each parent. Gametes are haploid.

Alleles

Each gene has two copies, one on each chromosome
Different versions of a gene are called alleles
Alleles can vary in their DNA sequence leading to different versions of a gene
Populations with genes having at least two alleles are considered genetically polymorphic

Genotypes and Phenotypes

Genotype refers to the combination of alleles an individual possesses e.g., AA, aa, Aa
Phenotype refers to the physical characteristics determined by the genotype and its interaction with the environment
Dominant alleles determine the phenotype when present in a heterozygote, a recessive trait only appears in homozygotes

Mendelian Inheritance

Traits can be followed in families using pedigrees
Inheritance patterns include: autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, Y-linked

Autosomal Dominant Inheritance

Disease phenotype appears when one copy of the gene is affected
Affected individuals are either homozygous or heterozygous for the dominant allele
The dominant allele is usually rare, thus most cases of AD disease are heterozygous
AD disease is more likely to be diagnosed in every generation, with affected individuals usually having an affected parent

Mechanisms of Dominance

Haploinsufficiency: 50% loss in gene product function leads to disease
Dominant Negative Effect: Abnormal protein interferes with the function of the normal allele
Gain of Function: Mutant protein has an enhanced function
Loss of Heterozygosity: Random loss of the normal allele in cells with an inherited mutant allele can lead to cancer

Autosomal recessive Inheritance

Disease phenotype appears only when both copies of the gene are affected
Heterozygotes are carriers of the recessive allele
Carriers are not at a selective disadvantage
AR diseases are more common than AD
AR families often display affected individuals in a single generation (horizontal pattern)
Parents of affected individuals are often carriers

Genetic Heterogeneity

Different genetic defects can result in identical or similar phenotypes
Allelic Heterogeneity: Different mutations in the same gene cause the same disease
Locus Heterogeneity: Mutations in different genes result in the same disease, often involving complex pathways that can be interrupted at multiple points

Examples of Genetic Heterogeneity

Phenylketonuria (PKU): Different mutations in the PAH gene (encoding phenylalanine hydroxylase) can cause varying degrees of PKU severity.
Retinitis Pigmentosa: Mutations in different genes involved in the visual pathway can lead to this retinal degeneration.

Mendelian Genetics

Genome: The complete genetic material of an organism, comprising 3 billion base pairs.
Chromosomes: Individual DNA molecules that organize the genome.
Humans have 23 pairs of chromosomes: 22 pairs of autosomes (homologous) and 1 pair of sex chromosomes (heterologous).
Diploid: Cells with two sets of chromosomes (n=46).
Haploid: Cells with one set of chromosomes (n=23).
Alleles: Different versions of the same gene, located at the same locus on homologous chromosomes.
Genetic polymorphisms: Genes with two or more alleles present in the population.
Genotype: The genetic makeup of an individual.
Phenotype: The observable characteristics of an individual resulting from the genotype and its interaction with the environment.
Dominance: One allele masks the expression of another allele.
Recessive: An allele whose effect is masked by a dominant allele.

Autosomal Dominant (AD) Inheritance

Disease phenotype: Only one copy of the gene needs to be affected for the disease to manifest.
AD traits expressed in: Homozygotes (AA) and heterozygotes (Aa).
Most AD cases are heterozygous: Homozygotes may be at a selective disadvantage and die before reproductive age.
Low allele frequencies: typically associated with AD diseases.

Mechanisms of AD Disease

Haploinsufficiency: Normal physiology requires more than 50% of the gene product.
- Loss of 50% normal activity of a protein leads to disease.
- Examples: LDL receptor in familial hypercholesterolaemia.
Dominant Negative Effect: Abnormal protein interferes with the function of the normal allele.
- Example: Collagen disorders, like osteogenesis imperfecta.
Gain of Function: Mutant protein function is enhanced.
- Examples: Achondroplasia and Huntington disease.
Loss of Heterozygosity: Inherited copy of a mutant gene and random loss of the normal allele leads to cancer.
- Examples: Retinoblastoma and Familial Adenomatous Polyposis.

Examples of AD Inheritance

Familial Hypercholesterolaemia: Reduced ability to remove LDL cholesterol from the bloodstream leading to atherosclerosis and early MI.
Huntington's Disease: Mutant huntingtin protein damages neurons.
Osteogenesis Imperfecta: Abnormal collagen leads to brittle bones.
Neurofibromatosis: Loss of neurofibromin protein allows uncontrolled cell growth (NF type 1).
Familial Adenomatous Polyposis: Damage to APC protein leads to colorectal tumor development.

AD Pedigree Characteristics

Vertical pattern:" phenotype appears in each generation.
Affected individuals have at least one affected parent.
Both sexes affected with equal probability.
Approximately 50% of offspring from an affected parent will be affected.

Most Common AD Mating Type

Aa + aa: A (affected allele) is typically present at low frequencies in the population.

Apparent Exceptions to AD Inheritance Pattern

Mutation: Sporadic cases in families can arise from a new mutation.
Variable Expressivity: The severity and nature of the phenotype can differ among individuals with the same genotype.
Reduced Penetrance: Not all individuals with the genotype exhibit the phenotype.

Autosomal Recessive (AR) Inheritance

Disease phenotype: Both copies of the gene must be affected for the disease to manifest.
Heterozygotes (Aa) are carriers: Do not have the disease but can pass the affected allele to their offspring.
AR diseases are more common than AD diseases.

AR Pedigree Characteristics

Horizontal pattern: Affected individuals tend to be in a single sibship, not seen in multiple generations.
Both sexes affected with equal probability.
When two carriers mate: ¼ affected, ½ carrier, ¼ normal.

Examples of AR Inheritance

Cystic Fibrosis: 1/1600 (USA) frequency, 1/20 is a carrier.
Phenylketonuria: 1/12000 frequency.
Albinism
Sickle Cell Anemia
α and β Thalassemia

Most Common AR Mating Type

Carrier x Carrier (Aa x Aa): ¼ AA (normal), ½ Aa (carrier), ¼ aa (affected).

Less Common AR Mating Types

Carrier x Affected (Aa x aa): ½ Aa (carrier), ½ aa (affected).
Normal x Affected (AA x aa): All Aa (carrier).

Problems in Pedigree Analysis

Uncertain Parentage
Small Family Size
Accurate Information about Relatives
De novo Mutation
Reduced Penetrance/Variable Expressivity
Genetic Heterogeneity

Genetic Heterogeneity

Different genetic defects can produce the same or similar phenotypes.
Allelic Heterogeneity: Different mutations in the same gene lead to the same phenotype.
Locus Heterogeneity: Mutations in different genes lead to the same phenotype. Often involves complex pathways where disruption at different points can lead to the same outcome.

Allelic Heterogeneity Example: Phenylketonuria (PKU)

Phenylalanine hydroxylase (PAH) converts phenylalanine to tyrosine: A defect in this pathway leads to a buildup of phenylalanine and phenylketones, which can cause mental retardation.
Multiple mutations in PAH exist: Some lead to milder forms of PKU with varying degrees of severity.

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Description

Explore the fundamental concepts of Mendelian genetics, including genome organization, alleles, genotypes, and simple inheritance patterns. This quiz covers the essential principles that govern how traits are inherited from one generation to the next.