3.4.2. Genetic diseases

Autosomal genetic diseases

Caused by a gene in an autosomal chromosome

Types of autosomal genetic diseases

Recessive, dominant and co-dominant

Recessive diseases

* Caused by recessive alleles


* Most common genetic disease

What phenotype develops the disease?

Individual must have two copies of the recessive allele in order to develop the disease

* Heterozygous

Carriers

Individuals who have one allele for the genetic disease and one dominant allele (i.e. heterozygous individuals)

Examples of recessive disease

Cystic Fibrosis

Cystic Fibrosis

Mutation to CFTR gene on chromosome 7

Normal role of CFTR gene

Codes for the production of chloride ion channels required for secretion of sweat, mucus and digestive juices

Effects of Cystic Fibrosis

Recessive alleles of affected gene produce malfunctioning chloride channels

* Sweat contains excessive sodium chloride, but digestive juices and mucus have insufficient sodium chloride
* Hence, not enough water moves into the secretions by osmosis, making them more viscous
* Sticky mucus builds up in the lungs, causing infections and respiratory failure
* Pancreatic duct is blocked (pancreatic cyst) so digestive enzymes secreted by the pancreas do not reach the small intestine

Chances of both parents being carriers

1/400

Dominant diseases

* Caused by a dominant allele
* Small proportion of genetic diseases

What phenotypes develop the disease?

Only one dominant allele of the gene is required to develop the disease

* Homozygous dominant (100% chance)
* Heterozygous (50%)

Example of dominant disease

Huntington’s disease

Huntington’s disease

Caused by the dominant allele of the HTT gene on chromosome 4

Normal role of HHT gene

Produced a protein called Huntington, whose function is unknown

Effects of Huntington’s disease

* Dominant allele causes degenerative changes in the brain
* Symptoms usually start between 30 to 50 years old
* Changes to behavior, thinking and emotions become increasingly severe
* Life expectancy after the start of symptoms is 20 years
* Individual eventually dies of heart failure, pneumonia or other infections

Co-dominant diseases

* Caused by co-dominant alleles


* Very rare

Genotype affected

In individuals carrying one normal allele and one affected allele, both are expressed

Example of co-dominant disease

Sickle cell anemia

Sickle cell anemia

* Normal allele for hemoglobin is Hb^A and the sickle cell allele is Hb^S
* Phenotype of individuals with one Hb^A and one Hb^S (heterozygous) differ from those who have two copies of either allele, so the alleles are co-dominant

Sex-linked genetic diseases

Caused by a gene in a sex chromosome

Sex linkage

When the ratios of inheritance for a disease are different in males and females

What causes sex linkage?

Sex-linked genes are only present on one sex chromosome and not the other, so the sex of an individual affects what alleles are passed onto offspring

What chromosome causes the majority of sex-linked diseases? Why?

X-chromosome

* Y chromosome is shorter and contains only a few genes, while the X is longer and contains genes not present in the Y

If the gene is on the X chromosome, how many copies will males vs females have?

Males (XY) → one copy

Females (XX) → two copies

X-linked dominant inheritance

More common in females because if ither chromosome (maternal or paternal) carries a dominant allele for the disease, the female will have it

X-linked recessive inheritance

More common in males because they only have one copy of the gene, so if they have the affected allele, they will express the disease

Carriers of X-linked recessive

Males → cannot be carriers as Y chromosome cannot mask the disease

Females → since they do not inherit affected gene from an unaffected father, they can be carriers

Example of X-linked recessive

Red-green colorblindness and haemophlia

Red-green colorblindness

Disorder in which the individual fails to discriminate between red and green

What causes red-green colorblindness?

A recessive allele of a gene that synthesizes photoreceptor proteins

Who is more affected by red-green colorblindness?

Males since the presence of an abnormal allele will necessarily given them the condition

Conditions for a female to be affected

Affected father + inherit the X-chromosome carrying the recessive gene from their mother

Conditions for a male to be affected

Mother is affected → 100% chance since mother must be homozygous recessive

Mother is carrier → 50% chance since mother is heterozygous

Haemophilia

Disorder in which the body’s ability to control blood clotting is impaired

What causes haemophilia?

A recessive allele of a gene that codes for a protein called factor VIII, which is needed to make blood clots

Alleles of factor VIII gene

Dominant F → codes for normal factor VIII

Recessive f → lack of factor VIII

Conditions for male vs female be affected

Same as red-green colorblindness

Pedigree charts

Used to investigate patterns of inheritance within a family

Autosomal dominant

* Cannot be recessive → two affected parents would not have unaffected offspring
* Parents must be heterozygous

Autosomal recessive

* Cannot be dominant → two unaffected parents would not have affected offspring
* Parents must be heterozygous

X-linked dominant

* Sex linkage cannot be confirmed
* 100% incidence of affected daughters from an affected father suggests X-linked dominance

X-linked recessive

* Sex linkage cannot be confirmed
* 100% incidence of affected sons from an affected mother suggests X-linked recessive