Week 12 - Simple Genetic Disorders

Question 1

What is a simple trait

Answer 1

Simple refers to that there is only one gene which impacts the mutation and that it is inherited in a Mendelian fashion

Question 2

What are 2 examples of simple genetic disorders

Answer 2

• Sickle Cell Anaemia
• Cystic Fibrosis

Question 3

What is sickle cell anaemia

Answer 3

Sickle cell anaemia is a genetic blood disorder characterized by abnormal hemoglobin, and is a common hereditary hematologic disease.

Question 4

What oral problems does sickle cell anaemia cause

Answer 4

• Delayed tooth eruption
• High rates of periodontitis
• Alterations in the cells of the tongue surface
• Enamel and dentin hypomaturation and hypomineralisation
• Pulp calcifications
• Bone alterations

Question 5

How does sickle cell anaemia occur

Answer 5

• This can occur through multiple different substitutions of nucleotides since there is redundancy in the genetic code
• This disease occurs when there is a substitution of glutamic acid into valine within the genome. This causes alterations to the structure of red blood cells into a sickle blood red (fibrous conglomerate of proteins).
• Despite the altered structure the altered genome can still form a hemoglobin cell which has the capacity to transport oxygen, however its capacity to transport is significantly reduced
• These mutated cells can block blood flow by building up in blood vessels

Question 6

What is the change in genome which causes sickle cell anaemia

Answer 6

Glutamic acid (Glu) into valine (Val)

Question 7

What is the concept of heterozygote advantage

Answer 7

The survival benefit of being heterozygote
- As malaria targets normal hemoglobin cells Neel theorized that individuals who where heterozygous with sickle cell amaemia would have a survival advantage as the mutated heterozygous cells wouldn’t be affected by malaria and would still be able to transport oxygene, enabling the survival of the individual
- An individual who’s heterozygous with sickle cell anaemia would produce both normal and sickle blood cells

Question 8

What is the disease management of sickle cell anaemia

Answer 8

This remains a challenge to manage

• Pain medication and NSAID to treat vaso-occlusive crisis
• Blood transfusion reduce the stoke rate to 1% pa (vs 10% without)

Question 9

What is curative treatment (curing the disease) for sickle cell anaemia

Answer 9

• Bone Marrow Transplant
• Gene therapy (in research only)
• Gene switching drugs

Question 10

What is the prognosis of sickle cell anaemia

Answer 10

• 90% survive to age 20
• 50% survive beyond age 50

Question 11

What is cystic fibrosis

Answer 11

Cystic fibrosis (CF) is a genetic disorder that primarily affects the lungs and digestive system, causing thick and sticky mucus to build up in these organs

Question 12

What type of genetic inheritance pattern is cystic fibrosis

Answer 12

autosomal recessive

Question 13

what oral problems can cystic fibrosis cause

Answer 13

• Higher incidence of enamel defect
• Higher rates of antibiotic use are associated with increased enamel problems and caries

Question 14

How does cystic fibrosis occur

Answer 14

Cystic fibrosis occurs due to the inappropriate build up of salt on one side of the epithelium layer, most commonly in the epithelium of the lungs.
Cystic fibrosis transmembrane conductance regulator (CFTR) gene is the gene which is responsible for the disease.
This gene is a chloride ion transporter, and when transported correctly it causes an appropriate amount of mucus build up on epithelial layers of the lung.
If the transmembrane regulator is broken there is a build up of chloride ions and a thickening of mucus on the outside.
This thickening of mucus makes it difficult for individuals to absorb oxygen across the epithelium, making breathing difficult. Additionally it promotes the attraction of bacteria to the epithelium, which is why high dosages of antibiotics is required in treatment.

Question 15

What gene is mutated in cystic fibrosis

Answer 15

Cystic fibrosis transmembrane conductance regulator (CFTR)

Question 16

How is cystic fibrosis developed through mutation

Answer 16

The development of cystic fibrosis can occur through multiple different types of mutations to the CFTR gene, with some mutations resulting in worst outcomes than others.

Question 17

What are the impacts of a mutation in CFTR caries between tissues

Answer 17

There is a wide variety of phenotypic outcomes from gene mutation

Important for salt and water balance in:

• lungs —> more infection
• Pancreas —> blocked ducts, pancreatitis
• Reproductive tract —> black vas deferens (male infertility)
• Skin —> increase salt loss in sweat
• Intestine —> reduced absorption

Question 18

What are secondary pathogenic mechanisms from cystic fibrosis

Answer 18

P. aeruginosa is a gram negative bacteria which can infect the lungs and form biofilm within it

• Chronic malnutrition ( and vitamin deficiencies
• Chronic infection
• Chronic exposure to antibiotics
• COPD in later life

Question 19

How do genetics allow scientists to precisely identify causative mutations for specific genetic diseases

Answer 19

They utilize a reference genome which is the average genome of all individuals to compare others individuals genome to identify mutations in the genome. From this we would associate the change to a disease.