lecture 5

Question 1

single gene disorder

Answer 1

disorders which occur due to alteration in one or both copies of a single gene

Question 2

autosomal gene

Answer 2

located on one of the 22 pairs of autosomes (non -sex chromosomes)

Question 3

autosomal dominant disease

Answer 3

an alteration in a single copy of an autosomal dominant gene has a recognizable clinical outcome

Question 4

what does the transmisson of a disease from male to male (father to son) show

Answer 4

shows us that the condition must be autosomal, non sex chromosomes

Question 5

penetrance

Answer 5

the percentage of gene carriers who carry a specific genetic variant and actually show clinical symptoms of that disorder.

Question 6

expression

Answer 6

how the genetic disorder is manifested (what symptoms and clinical features are observed)

Question 7

what is important to note about people who have an autosomal dominant disorder

Answer 7

they also have family members who are at risk of inheriting the disease

Question 8

familial hypercholesterolemia symptoms

Answer 8

• higher levels of cholesterol means that plaque builds up in the arteries which can lead to coronary artery disease
• little lumps of fatty tissue

Question 9

how common is familial hypercholesterolemia

Answer 9

1 in 500

Question 10

cholesterol

Answer 10

ingested in the diet
synthesized and secreted from the liver

Question 11

how is cholesterol removed from circulation

Answer 11

via LDL (low density lipoprotein) complex

LDL particles in the bloodstream carry cholesterol.
LDL particles bind to LDL receptors

Question 12

stages of LDL receptor synthesis in the hepatocyte

Answer 12

1. abnormality of LDL receptor synthesis
2. abnormality of transport to golgi apparatus
3. abnormality of LDL binding by receptor
4. abnormality of receptor clustering in coated pit

Question 13

Type 1 Neurofibromatosis

Answer 13

• multiple benign skin tumors and multiple brown skin patches
• full penetrant but variable expression

Question 14

Marfan syndrome

Answer 14

• tall stature, long limbs, loose joints, dislocated lense
• fully penetrant with variable expression

Question 15

Huntington Disease

Answer 15

• manifests with abnormal limb movements, mood changes, progressive dementia
• incurable
• children of person with HD have 50% chance of having abnormal HD gene

Question 16

Familail Adenomatous Polyposis

Answer 16

• fully penetrant
• develop benign colonic polyps (growths that develop on the inner lining of the colon or rectum)
• untreated will progress to colon cancer

Question 17

Achondroplasia

Answer 17

• short limbed short stature, and macrocephaly (large head)
• fully penetrant and has a consistent expression.
• high new mutation rate, most people being born to normal stature parents

Question 18

inheritance of achondroplasia

Answer 18

although a person with achondroplasia is often born to unaffected parents, when that person becomes an adult there is a 50:50 chance of each of their children being similarly affected if there partner is unaffected

Question 19

results when both parents are affected by a autosomal dominant disorder

Answer 19

• 1 in 4 chance of child being unaffected
• 2 in 4 chance of child with the same condition their parent has
• 1 in 4 chance of being homozygous, more severely affected

Question 20

haploinsufficiency

Answer 20

genetic condition in which a single functional copy of a gene is not sufficient to maintain normal function

Question 21

homodimer

Answer 21

gene product interacts with itself

Question 22

heterodimer

Answer 22

gene product interacts with products of other genes

Question 23

dominant negative pathogenic variants

Answer 23

genetic mutations that result in the production of a mutant protein that interferes with the production of the normal protein

Question 24

dominant negative pathogenic variant - Marfan syndrome

Answer 24

fibrillin 1 protein monomers polymerise together to make microfibrils
partly functional pathogenic variant will produce unstable protein

Question 25

Dominant negative pathogenic variant - Osteogenesis Imperfecta

Answer 25

Type 1 collagen genes produce collagen proteins which are expressed in bone missense pathogenic variants in Col1A1 destablise triple protein helix causing Oesteogenesis Imperfecta

Question 26

Charcor Marie Tooth disease

Answer 26

- slowly progressive weakness and loss of feeling in lower legs - high arches absent reflexes