Genetics Flashcards
1
Q
How many chromosomes do we have
A
23 pairs
46 total
2
Q
How much breast cancer is hereditary
A
5-10%
3
Q
How much ovarian cancer is hereditary
A
5-10%
4
Q
How many women will get breast cancer
A
1 in 8
5
Q
How many women will get ovarian cancer
A
1 in 70
6
Q
Which genes cause hereditary susceptibility to CRC
A
HNPCC
FAP
7
Q
What occurs during G1 of cell cycle
A
First cell growth
8
Q
What happens during G0 phase of cell cycle
A
Cells go into resting
9
Q
What occurs during G2 of the cell cycle
A
2nd growth phase
10
Q
What occurs during the M phase of the cell cylce
A
Mitosis
Cell division
11
Q
Which 2 types of gene mutation are there
A
Germline mutation
Somatic Mutation
12
Q
What is germline mutation
A
Mutation that is present in the egg
Heritable
Cause cancer family syndromes
Only types of mutation that can be passed onto offspring
13
Q
What are somatic mutations
A
Occur in non-germline cells
Non-inheritable
How most cancers occur
Random mutation in a cell
14
Q
Are most cancers somatic or germline mutations
A
Somatic
15
Q
Which type of mutation is heritable
A
Germline mutation
16
Q
What is an oncogene
A
A gene that has the potential to cause cancer
17
Q
Describe the multistep carcinogenesis in colon cancer
A
Loss of APC
Activation of K-rar
Loss of 18q Loss of TP53
Other alterations
18
Q
What is non-sense mutation
A
When a change in base causes a stop code to be coded for
This causes premature halt in the protein making
19
Q
What a mis-sense mutation
A
When a single base substitution codes for an amino acid which doesn’t make the original sense but is not non-sense
20
Q
Another name for HNPCC
A
Lynch syndrome
21
Q
What cancers is HNPCC at risk for
A
CRC Endometrial Urinary tract Ovarian Gastric cancers
22
Q
Which type of CRC cancer develops in in HNPCC
A
Adeno-carcinoma sequence from poly formation
23
Q
Clinical features of HNPCC
A
Early but variable age at Dx of CRC
(45r average)
Tumour site in proximal colon predominates
FH of CRC
24
Q
Which genes are associated with breast cancer and ovarian cancer
A
BRCA1 and BRC 2
25
What is the risk of breast cancer in BRCA genes
60-80%
| Often early age onset
26
What is the risk of ovarian cancer in BRCA genes
20-50%
27
What is the risk to males of the BRCA genes (especially 2)
Increased risk of prostate cancer and breast cancer
28
What is a prophylactic option for those with the BRCA genes
Prophylactic double mastectomy and hysterectomy
29
Describe autosomal dominant inheritance
Each child has 50% chance of inheriting
No skipped generations
Equally transmitted by males and females
30
When should you suspect hereditary cancer syndromes
Cancer in 2 or more close relatives
Early age Dx
Multiple primary tumours
Characteristic pattern of tumours (e.g breast and ovarian, endometrial and bowel)
Evidence of autosome dominant transmission
31
What are the options for breast cancer surveillance
```
Breast awareness
Early clinical surveillance
Annual clinical beast exams
Mammography (moderate/high 2yrly from 35-40, yearly from 40-50)
MRI screening those at highest risk
```
32
Describe prophylactic mastectomy
Removed both breasts
| Significantly reduced risk of breast cancer
33
Describe prophylactic oophorectomy
Eliminates risk of primary ovarian cancer
However peritoneal carcinomas may still occur
Induced surgical menopause so give HRT
34
How is genetic risk estimation classified
High
Moderate
Low
35
What is the surveillance option for CRC
Colonoscopy
High risk: 2yrly from 25
Moderate risk: 2yrly 35-55
36
Surveillance option for endometrial cancer
Look for PMB
Transvaginal USS
Surgery
37
Benefits of cancer surveillance
Identifies high risk
Identifies non-carriers in families with a known mutation
Allows early detection and prevention strategies
May relieve anxiety
38
Risks of cancer surveillance
Does not detect all mutations
Continued risk of sporadic cancer
Efficacy of interventions variable
May result in psychosocial
or economic harm
39
What is a multi-system disorder
Disorder that affects more than one system (often several)
40
Which structural chromosomal mutations can cause multi-system dis
Translocations
Deletions
Micro-deletions
Numeracy: eg Trisomy
41
Example of numerical chromosome mutation that can cuase multi-system dis.
Trisomy 21
| Down Syndrome
42
What type of inheritance is Myotonic dystrophy and Neurofibromatosis 1
Autosomal dominant
43
What type of inheritance is CF
Autosomal recessive
44
How many copies of the gene are needed in autosomal dominant
1 copy
45
How many copies of the genes are needed in autosomal recessive
2 copies of the gene
46
What type of inheritance is Duchenne Muscular Dystrophy
-linked
47
Why do some genes cause multi-system involvement
Several genes with diverse functions are involved
Single gene is widely expressed
Single gene tissue specific expression but tissue integral part of many different system
48
Inheritance of neurofibromatosis Type 1
Autosomal dominant
49
Pathology of neurofibromatosis Type 1
Causes tumours to grow along nerves
50
NIH diagnostic criteria for neurofibromatosis type 1
```
Need 2+ for Dx
Cafe au lait spots (6 or more)
Neurofibromas (2 or more)
Axillary freckling
Lisch nodules (speks in iris)
Optic glioma
Thinning of long bone cortex
FH
```
51
Further features of NF1
```
Macrocephaly
Short stature
Dysmorphic features
Learning Difficulties
Epilepsy
Scoliosis
Pseudoathrosis
Raised BP
Neoplasia
```
52
Dx of NF1
Clinical Dx using NIH criteria (2+ of criteria)
53
Rx for neurofibromatosis
Annual review of affected individuals and at risk children until diagnosis can be excluded (5 years)
BP
Spine for scoliosis
Tibia for unusual angulation
Visual acuity and visual fields
Educational assessment
Ask patient to report any unusual symptoms
54
Which gene has been identified with NF1
17q
55
What is meant by variable expression
Inter-familial and intra-familial difference on the gene expression
Therefore different extent of the disease
56
Are NF1 and NF2 the same
NO completely different disorders
57
Where is the NF2 gene
Chromosome 22
58
Main features of NF2
Acoustic neuromas (usually bilaterally)
CNS and spinal tumours
Few cafe au lait spots
59
Classic triad of tuberous sclerosis
Epilepsy
Learning difficulties
Skin Lesions
60
Type of inheritance in tuberous sclerosis
Autosomal dominant
61
Pathology of tuberous sclerosis
Hamartomas in different organs
62
Clinical features of tuberous sclerosis
Multi-system
Learning difficulties
Seizures
63
Other features of tuberous sclerosis
Skin lesions
- depigmented macules
- angiofibromas
- fibrous plaque forehead
- shagreen patches
- Subungual fibromas
Kidney
-cysts and angiomyolipomata
Phakomas in eye
- benign unless on macula
Rhabdomyomas in heart
64
Screening of at risk relatives of tuberous sclerosis
```
Surveillance and genetic counselling
Clinical examination (skin signs, nails, retina examination)
Cranial MRI
Renal USS
ECHO
```
65
What type of inheritance is myotonic dystrophy
Autosomal dominant
66
What are the 2 types of myotonic dystrophy
DM 1
| DM 2
67
Clinical features of myotonic dystrophy
```
Muscle weakness
Cataracts (bilateral)
Muscle stiffness
Myotonia
Gradual muscle loss
Muscle wasting
DM
Bowel problems
Low motivation
Heart block
```
68
What can occur in myotonic dystrophy after anaesthetic if not closely monitored
Death
Need to be make anaesthetists aware!
69
What is the gene pathology of myotonic dystrophy
CTG repeat
| exhibits anticipation with increasing severity in each generation
70
Why is Myotonic Dystrophy a multi-system disorder
Because it affect multiple systems
71
What is cascade testing
The identification of close relatives of an individual with a disorder to determine whether the relatives are also affected or are carriers of the same disorder. It is intended as a form of medical screening.
72
What aetiological factors contribute to adult onset disease
Genetic
| Environmental
73
Why are adults referred to genetic services
```
For a Dx
For predictive testing
Carrier testing or cascade screening
Family history
Fetal loss or recurrent miscarriage
```
74
Is Huntington's due to genetic or environmental factors
Purely genetic factors
75
Is scurvy due to genetic or environmental factors
Purely environmental
76
4 principles in ethics
Respect for autonomy
Beneficence
Non-maleficence
Justice
77
Aetiology of Amyotrophic Lateral Sclerosis (MND)
Generally sporadic
Mean onset age 55yrs
5-10% familial
78
Clinical features of MDN
```
Progressive muscle weakness, wasting and increased reflexed
Limb and bulbar muscles involved
Purely motor signs
No sensory signs
Cognition spared
Death due to rep. failure
```
79
Which enzyme/gene has been implicated in familial amyotrophic lateral sclerosis
```
Superoxide dismutase
(20% of familial case, 2% of all cases)
```
80
Primary function of superoxide dismutase
Catalyses conversion of intracellular superoxide radicals produced during normal metabolism
Protects many cell types from free radical damage
81
What are the 3 forms of superoxide dismutase
SOD1 (cytoplasm)
SOD2 (mitochondria0
SOD3 (extracellular)
82
Features of X-linked inheritance
Males are affected in >1 generation
No affected females
Affected males are linked through unaffected females
Males do not transmit to males
83
What type of inheritance if Huntington's disease
Autosomal dominant
84
Movement clinical features of Huntington's Disease
```
Movement:
Chorea
Athetosis
Myoclonus
Rigidity
```
85
Cognitive clinical features of Huntington's disease
Cognitive:
Poor planning and memory
Subcortical dementia
NO classical dementia
86
Personality clinical features of Huntington's disease
```
Irritable
Apathetic
Loss of empathy
Disinhibition
Self-centred
```
87
Psychiatric clinical features of Huntington's Disease
Depression
Paranoia
Psychosis
88
Onset of Huntington's
Late 30yrs early 40s typically
| But variable
89
Penetrance in Huntington's
Fully penetrant
90
Cure for Huntington's
No cure
| Unsatisfactory treatment
91
Advantages of predictive testing for HD
Uncertainty of gene status removed
->If negative:
Concerns about self and offspring reduced.
-> If positive:
Make plans for the future
Arrange surveillance/treatment if any
Inform children/decide whether to have children
92
Disadvantages of Huntington's Predictive testing
```
->If positive:
removes hope
continues uncertainty
when is this disease going to present?
Becomes a question on when?
known risk to offspring
impact on self/partner/family/friends
potential problems with insurance / mortgage.
```
->If negative:
expectations of a ‘good’ result
‘survivor’ guilt.
93
Who do genetic Dx affect
Impact the whole family
