Autosomal Dominant Conditions

Question 1

Haploinsufficiency

Answer 1

Single loss-of-function allele leads to reduction in amount of normal product to a degree that is insufficient for a normal phenotype
Autosomal dominant inheritance

Question 2

Dominant negative mutation

Answer 2

Mutant allele reduces or eliminates function of normal one

Caused by altered protein product, yielding a more severe phenotype than would be caused by a null allele alone

Question 3

Hypermorph/gain of function

Answer 3

One allele produces more product than the other

Question 4

Neomorph/gain of function

Answer 4

Change in gene that causes increase in function

Question 5

Incomplete penetrance

Answer 5

Environment or other genes mask(s) phenotype

Question 6

How a dominant trait can be present in offspring but not parent

Answer 6

Germline mosaicism
Mutation is only present in gonads (not somatic cells)
Parent carries mutations in germ line, but doesn’t express disease phenotype

Question 7

Mutation in alpha-1-antitrypsin

Answer 7

Normal function: inhibit elastase (breaks down elastin)
Mutation changes recognition of elastase to thrombin inhibition
Thrombin is necessary for blood clot formation
Bleeding disorder results
Too much elastase activity: severe lung damage (COPD)

Question 8

Type of dominant disease that alpha-1-antitrypsin is

Answer 8

Gain of function neomorph: new function (inhibition of thrombin instead of elastase)
Loss of function: no elastase inhibition

Question 9

Genes associated with osteogenesis imperfecta

Answer 9

COL1A1 and COL1A2

Both code for collagen

Question 10

Osteogenesis imperfecta type 1

Answer 10

Frequent fractures beginning when child starts to walk, development of thin and bulging vertebrae later in life, very flexible joints, blue sclerae (white part of eyes)
Structure of type 1 procollagen is normal, but production of type 1 procollagen is decrased
Half of usual amount of pro alpha 1 chains: inability to assemble into collagen molecules

Question 11

Type of dominant mutation that results in osteogenesis imperfecta type 1

Answer 11

Haploinsufficiency

Half of normal type 1 collagen molecules are formed

Question 12

Type of dominant mutation that results in osteogenesis imperfecta type 2

Answer 12

Dominant negative

Abnormal type 1 collagen

Question 13

Osteogenesis imperfecta type 2

Answer 13

Very soft skull, frog-leg position (legs bowed, hips flexed), dark sclerae, beaked nose
About half die within first 24 hours after birth (usually due to respiratory failure or cerebral hemorrhage)
Caused by improperly formed collagen or prevention of collagen secretion

Question 14

Achondroplasia

Answer 14

Autosomal dominant condition
Short limbs, but larger than average head
90% result from new mutation

Question 15

Mutation that causes achondroplasia

Answer 15

Mutation in gene for fibroblast growth factor receptor 3

Fibroblast growth factor receptor 3 limits osteogenesis: mutation causes activation of receptor