Genetics 2 Lecture

Question 1

What are the classification of genetic disorders?

Answer 1

Medelian disorders
Multi-factorial disorders
Single-gene disorders with nonclassic inheritance
Chromosomal disorders

Question 2

Define medelian disorders

Answer 2

Gregor Mendel
Results of expressed mutations in single gene
- A single mutant gene may lead to many end effects (pleiotropism)
- Mutations at several genetic loci may produce the same trait (genetic heterogeneity)

Question 3

Define Autosomal Dominant Disorders

Answer 3

• Fifty-fifty chance
  Mutations affect structural or regulatory proteins
  Product of the mutant allele may interfere with the function of the normal protein
  Reduction in penetrance and variable expressivity
  Dd –> doesn’t need two DD
  Disorder frequency: 1:2

Question 4

Example of Autosomal Dominant Disorders

Answer 4

LDL receptor pathway and regulation of cholesterol metabolism
Defects in receptor proteins
–Hypercholesterolemia results from mutation in gene encoding receptor for LDL

Question 5

Define Autosomal Recessive Disorders

Answer 5

-One in four chance
Most inborn errors of metabolism
Age of onset is early in life
Clinical features are more uniform
Enzyme proteins, rather than strctural proteins are affected
Two defective copies are required
50% chance of being a carrier and a 25% chance of inheriting the disorder

Question 6

Example of Autosomal Recessive Disorders

Answer 6

Pathogenesis of lysosomal storage diseases

• Complex substrate is normally degraded y series of lysosomal enzymes into soluble products
• If there is deficiency/malfunction of 1 of the enzymes, catabolism is incomplete and insoluble intermediates accumulate in the lysosomes

Question 7

What are disorders associated with defects in enzymes?

Answer 7

Gycogensoses: resulting from defects in synthesis is or catabolism of glycogen

• In the liver, causes deficiency of hepatic enzyme Glc-6P which is essential for creation of glucose
• Causes accumulation of Glycogen and low blood glucose (hypoglycemia)

Question 8

Define sex linked disorders

Answer 8

One normal copy of a gene on the X chromosome is generally sufficient for normal function
Women are protected by a normal gene on their other X chromosomes but men lack this protection
Male child of a mother carrier has a 50% of getting the disorder
- Almost all are X linked –> father to daughters and mothers to son

Question 9

What is Hemophilia A & B?

Answer 9

Rare inherited bleeding disorder in which the blood does not clot normally

Question 10

Define hemophilia A

Answer 10

Fact VIII deficiency

- 80% of cases

Question 11

Define hemophilia B

Answer 11

Factor IX deficiency
- Majority of the 20% cases left
Clotting accelerating factors work together to activate factor X in the coagulation cascade
Degree of expressivity varies

Question 12

Define X-linked Dominant Disorder

Answer 12

Caused by dominant disease alleles on the X chromosome

Question 13

How are X-linked Dominant Disorders transmitted?

Answer 13

an affected heterozygous female to half her sons and half her daughters
An affected heteroxygous male to all his daughters and none of his sons

Question 14

Examples of x-linked dominant disorder?

Answer 14

Vitamin D resistance rickets
(point mutation on Vitamin D receptor –> failure of normal signaling
– Decrease reabsoprtion of P by renal tubules (causing hypophosphatemia)
– Decrease absorption of Ca and phosphorous from GI tract
– Degree of expressivity varies