Genetics and Health Week 6

Question 1

Define Expression

Answer 1

The severity of mildness of the phenotype, influenced by the allelic variants in other genes and environmental factors

Question 2

Define Penetrance

Answer 2

The measure of the chance that an individual will actually develop symptoms at all
• Fully penetrant (100%)
• Partial penetrant (60%)

Question 3

Name the Descriptive Classes of Alleles

A) Hypomorphic
B) Neomorphic
C) Antimorphic
D) Hypermorphic

Answer 3

A) Hypomorphic: An allele that produces a decreased level of the protein’s activity

B) Neomorphic: An allele with a new activity or novel protein product

C) Antimorphic (Dominant Negative): An allele that antagonizes the activity of the normal gene product

D) Hypermorphic: An allele that produces an increased level of the protein’s activity

Question 4

What is the difference between Achondroplasia and Hypochondroplasia?

Note:

What type of disorder for each?
Mutation
Function (Decreased or Inhibited)
Result/ Clinical Feature

Answer 4

Achondroplasia
 Autosomal dominant
 Mutation is a gain of function
 Decreased endochondral ossification
 Inhibited proliferation of chondrocytes
 Decreased cartilage matrix production
 Abnormal bone growth, resulting with disproportionate short arms and legs, a large head
 Increased risk for death infancy from compression of the spinal cord and upper airway obstruction

Hypochondroplasia
	Missense mutation (p.Asn540Lys) 
	Milder compared to achondroplasia 
	Trunk length is often mild 
	Short stature with disproportionate limbs

Question 5

Define Huntington’s Disease

What type of disorder?
What gene is affected and what happens?
Function
Result (Brain)/ Clinical Features

Answer 5

 Affects the HTT gene
 Glutamine repeats within the huntingtin protein
 Leads to an aggregation of protein
 Occurs in the age of 30-50 years old, 2 is the earliest
 50% chance of inheriting the disorder
 The disease develops if you live long enough
 Symptoms appear well after he reproductive age
 No treatment no cure
 Autosomal dominant
 Cells in the caudate nucleus of the brain begin to decease

Clinical features: Chorea (jerky involuntary movements affecting the shoulders, hips and face), voluntary movement, cognitive decline,

Question 6

Define Anticipation (2)

Answer 6

• Increasing disease severity and/or earlier age
• Commonly in paternal transmission
• Arises from the instability of the CAG repeat during spermatogenesis

Question 7

Define Myotonic Dystrophy

What type of disorder
Mutation
Function
Result

Answer 7

• Progressive muscle wasting and weakness
• Affects smooth muscle, eye, heart, endocrine system, and central nervous system
• Categorized into three overlapping phenotypes (mild, classical and congenital)
• CTG trinucleotide repeat in the DMPK gene, autosomal dominant
• Use of ankle-foot orthoses, wheelchairs, treatment of hypothyroidism, management of pain
• CTG repeat length exceeding 37 repeats is abnormal

Question 8

Define Retinoblastoma

What type of disorder?

Mutation

Answer 8

• A malignant tumor arising in the retina of one or both eyes
• Fetal development (rapid division of retinoblasts)
• Rb is a tumor suppressor protein
• Loss of function of both alleles
• Still Dominant, affected individual already carries a chromosome with the mutant form of the retinoblastoma gene
• Requires two hits in each allele
• People who carried one defective allele in all their cells had a greater chance of contracting the disease, will be bilateral and have multiple foci
• Loss of a tumor suppressor gene

Question 9

Define Neurofibromatosis

Mutation
Function
Result
Clinical features

Answer 9

Neurofibromatosis Type 2: growth of noncancerous tumors in the nervous system, leading to deafness

 Mutations in NF2 gene (tumor suppressor protein merlin)
 Tumors can develop elsewhere in the nervous system
 NF1 alleles associated with disease include: missense, nonsense, insertions and deletion mutations, all cause partial or complete loss-of-function
 NF2 alleles include missense, nonsense and frame-shift mutations, cause partial or complete loss-of-function
 Swelling of a peripheral nerve that is caused by thickening of the nerve sheath or connective tissue
 The first mutated allele is inherited from the parents
 The second allele is somatically inactivated