Lecture 10 Introduction to genetics and human genetic diseases

Question 1

Terminology

Answer 1

Mutation: Permanent alteration of a gene

Allele: An alternative form of a gene

Homozygous: Two identical alleles for the same gene

Heterozygous: Two different alleles for the same gene

Genotype: The alleles carried by the individual

Phenotype: The observable traits of an individual

True-breeding: Organism that possess a phenotype that is always transmitted to the offspring.

Haploid: A genome that contains a single set of chromosomes
- prokaryotes, meiotic simple eukaryotes like yeast, germ cells, gametes

Diploid: A genome that contains paired chromosomes
- most somatic cells of most animals, and some plants like garden peas.

Question 2

Human Gametes and Zygote

Answer 2

Egg and Sperm are the human gametes

Human gametes are haploid

Zygote is the cell that results from the fusion of the gametes

Human zygotes are diploid

Question 3

What is a permanent change in a gene?

Answer 3

Mutation

Question 4

What is the ploidy of a gamete?

Answer 4

Haploid

Question 5

Law of dominance: The cross-hybridization experiments

Answer 5

All hybrid individuals have the same phenotype (purple) – this is the dominant phenotype.

The masked phenotype (white) is termed recessive

Question 6

Law of dominance: What genotypes are produced by the cross?

Answer 6

Both parents are homozygous because they are true-breeding.

All F1 hybrids have the same genotype and are heterozygous (P/p).

Plants with the same genotype have the same phenotype

Question 7

Summary
1

Answer 7

Garden peas are diploid organisms

The genotype of a cross of two pure-breeding lines is always heterozygous, i.e. have a pair of different alleles.

The phenotype of the heterozygous individual is termed the dominant

The phenotype of the masked allele is termed recessive.

Only discrete phenotypes controlled by a single gene follow a dominant/recessive inheritance pattern

There are phenotypes that do not follow the dominant/recessive pattern.

Question 8

What is the genotype of an F1 hybrid?

Answer 8

Heterozygous

Question 9

What is the phenotype of an F1 hybrid?

Answer 9

Dominant

Question 10

Law of segregation

Answer 10

Parental alleles are segregated into different haploid gametes with equal probability

Question 11

Law of segregation: The Self-Fertilization Experiment

Answer 11

Hybrid plants (Heterozygous) are self-fertilized

The offspring differs from parental line and the recessive phenotype is expressed again
The purple-to-white ratio is 3.15:1

Question 12

Law of segregation: What are genotypes of the F2 generation?

Answer 12

Frequency of genotypes in the offspring:
All possible genotype combinations are generated in a hybrid cross, but with different frequencies:
-1/4 Homozygous dominant (PP)
-2/4 Heterozygous (Pp)
-1/4 Homozygous recessive (pp)

Frequency of phenotypes in the offspring:
-¼ of all plants have white flowers (recessive)
-¾ of all plants have purple flowers (dominant)
-The Mendelian ratio of a hybrid cross is 3 : 1

Question 13

Summary 2

Answer 13

A diploid organism transmits a randomly selected allele to its offspring, such that the offspring receives one allele from each parent.

The offspring of an hybrid cross can express dominant or recessive phenotypes
-The frequency of the dominant phenotype is ¾
-The frequency of the recessive phenotype is ¼

Frequency of genotypes in the offspring is:
-1/4 Homozygous dominant (PP)
-2/4 Heterozygous (Pp)
-1/4 Homozygous recessive (pp)

All 3 possible genotypes can be produced in a hybrid cross

Question 14

What is the F2 frequency of the dominant and recessive phenotypes?

Answer 14

75% dominant and 25% recessive

Question 15

Law of independent assortment

Answer 15

Genes for different phenotypes are sorted separately from one another so that the inheritance of one phenotype is not dependent on the inheritance of another.

Question 16

Law of dominance

Answer 16

In a cross of parents that are true-breeding for contrasting phenotypes, only one form of the phenotype is expressed in the offspring – the dominant phenotype.

Question 17

Summary
3

Answer 17

Alleles for different phenotypes are distributed to sex cells independently of one another.

Law of independent assortment always apply for “Mendelian” phenotypes controlled by genes located in different chromosomes.

However, not all phenotypes segregate independently. The alleles of genes located very close to each other in the same chromosome can be inherited together, causing dependent assortment. This happens if recombination did not occur between the two genes during meiosis

Question 18

Alleles in different chromosomes are :

Answer 18

Inherited Separately

Question 19

Human Mendelian (monogenic) diseases

Answer 19

Monogenic disorders are caused by a mutation in a single gene.

The mutation may be present on one or both chromosomes

Question 20

Patterns of inheritance of monogenic diseases

Answer 20

One of the parents must have the disease for offspring to have the disease.

When both parents do not have disease, disease is not dominant

Both parents need to be at least heterozygous carriers for offspring to have disease

Disease may skip generations. Neither parents may have disease, but their children could be affected.

Mother must be at least a carrier for offspring to have disease
Sex-bias in the prevalence of disease: more frequent in males

Question 21

Summary
4

Answer 21

A family pedigree can help diagnose the inheritance pattern of a monogenic disease:

Autosomal dominant requires at least one of the parents to be affected.

If neither parent is affected you can exclude dominance and conclude it is a recessive disease (autosomal or sex-linked)

All the diseases discussed in this lecture are monogenic diseases, but…

Polygenic diseases: Several alleles acting together contribute to occurrence and severity of the disease

Genetic heterogeneity: Many mutations may result into the same disease (i.e. retinitis pigmentosa caused by mutations in any one of 60 diff genes)

What is the effect of the environment? Nature vs nurture

Question 22

In order to suffer from Huntington disease (dominant monogenic) and individual must have:

Answer 22

At least one of the parents affected

Question 23

In order to suffer from cystic fibrosis (monogenic recessive) and individual must have:

Answer 23

Both parents that are carriers

Question 24

A male individual will suffer from haemophilia (X-linked recessive) if:

Answer 24

His mother is at least a carrier

Question 25

A family with parents and son affected but with one daughter unaffected

Answer 25

Only dominance is consistent with this pedigree.

Recessive inheritance is inconsistent because both parents must have two copies of the mutant allele to have disease. Therefore, the offspring of parents with a recessive disease must be homozygous recessive and thus must be affected

Question 26

A family with parents and son unaffected but with one daughter affected

Answer 26

Only recessive inheritance is consistent with this pedigree.

Dominance is inconsistent because at least one of the parents must have disease for the phenotype to be dominant. In this case the parents are both carriers but do not have disease. Therefore, the mutant allele does not cause a dominant phenotype

Question 27

A family with a higher frequency of males affected

Answer 27

X-linked recessive diseases show gender imbalance in disease frequency
For male offspring to be affected the mother must be at least a carrier.

For females to be affected there are two requirements: the father must be affected and the mother must be at least a carrier.

Therefore, females are less frequently affected than males. Therefore, a sex-bias helps to distinguish X-linked from autosomal diseases.

Question 28

Law of segregation: Mechanism

Answer 28

Each gene has a pair of alleles.

Parental alleles are randomly separated to the sex cells so that sex cells contain only one allele of the pair.

Offspring inherit one genetic allele from each parent when sex cells unite in fertilization.

Therefore, parental alleles are segregated into different haploid gametes with equal probability. This is the law of segregation

Question 29

Law of independent assortment: Mechanisms

Answer 29

When recombination occurs, the alleles of genes A,B, and C will be inherited independently of the alleles in gene D and E. Notice that the chromosome of each gametes has a different combination of alleles

If recombination does not occur between two genes, the parental alleles of these genes are inherited together causing dependency between the phenotypes controlled by these genes.