Genetics Flashcards
1
Q
What phase of cell cycle do chromosomes condense enough for karyotyping
A
metaphase
2
Q
Haploinsufficiency
A
Reduction by about half in amount of protein usually due to whole gene deletion or frameshift mutation
3
Q
Silent mutation
A
changes that don’t affect the A.A produced by the codon
4
Q
Missense mutation
A
Change that affects the A.A produced by the codon
5
Q
Nonsense mutation
A
Change that results in a stop codon
6
Q
Frameshift mutation
A
Alters the reading frame, may lead to entirely different protein or a stop codon
7
Q
Locus
A
The location of a gene on a chromosome
8
Q
Allele
A
an Alternative variant of a particular gene
9
Q
Polymorphism
A
where there are at least 2 or more relatively common alleles of a gene in a the population
10
Q
Penetrance
A
on/off binary concept
Expressed or not expressed
Incomplete penetrance: may be age dependent like in huntington’s
11
Q
Expressivity
A
Variability of clinical features/phenotype in people with the same genotype
12
Q
Aneuploidy
A
an abnormal number of chromosomes
13
Q
47 XXY condition and presentation
A
Klinefelter Syn
- Primary hypogonadism
- Low testosterone
- Infertility, incomplete virlisation, gynecomastia
- tall stature
- mild learning difficulty, shy, emotionally immature
14
Q
45 X condition and presentation
A
Turner Syn
- Short stature, shield chest
- Webbed neck
- Infertility, ovarian dysgenesis
- Bicuspid Aortic valve, CoA
15
Q
Inheritance of myotonic dystrophy
A
Triplet repeat disorder
-Maternal
16
Q
Inheritance of huntington’s
A
Triplet repeat disorder
-Paternal
17
Q
Inheritance of Spinocerebellar ataxia
A
Triplet repeat disorder
-Gender of transmitting parent can modify symptoms in child
18
Q
Anticipation
A
The observation that a particular phenotype seems to be increasing in severity in subsequent generations
19
Q
CpG islands
A
on promoter regions of genes and is the mechanism of regulating gene transcription
20
Q
ncRNA
A
Non coding RNA
-Does not code for protein, but mediates gene regulation processes
21
Q
What is gene expression influenced by
A
conformation of chromatin
methylation of DNA
Availability of transcription factors
22
Q
Inheritance of Prader-Willi
A
Loss of paternally active 15q gene copy
- Paternal imprinting
- Paternal microdeletion
- Maternal UPD15
23
Q
Inheritance of Angelman Syndrome
A
Loss of maternallly active 15q gene copy
- Maternal imprinting
- Maternal microdeletion
- Paternal UPD15
- UBE3A mutaton
24
Q
RB1 -Condition and inheritance
A
AD
Retinoblastoma
Other features:
-melanoma
Osteosarcoma
Soft tissue cancers
25
Most familial cancers are due to germ line mutations in tumor suppressor genes rather than proto-onogenes except:
RET gene mutation - MEN 2
26
MENIN gene
MEN 1
| AD inheritance
27
Features of MEN 1
Parathyroid adenoma
Pituitary adenoma
Pancreatic islet cell/GI adenoma
28
RET gene
MEN2
| AD inheritance
29
MEN2a features
Medullary thyroid cancer
Phaochromocytoma
Parathyroid hyperplasia
30
MEN2b features
Medullary Thyroid cancer
Phaeochromocytoma
Neuromas/fibromas + marfanoid features
31
Inheritance of BRCA mutation
AD, highly penetrant
32
TP53 gene mutation
Li Fraumeni syndrome
| AD inheritance
33
Li Fraumeni syndrome features
SBLA
-Sarcoma, Breast, leukemia, adrenal gland cancers
Very young onset usually (before 30 yo)
34
Role of p53 in cancer
Tumor suppressor gene
If DNA is damaged, p53 prevents malignant transformation by delaying cell cycle progression
-Allows cell to initiate DNA repair or can initiate apoptosis
35
PTEN gene mutation
Cowden Syndrome
| AD inheritance
36
Features of Cowden syndrome
Breast cancer and Skin changes
| Papillary thyroid cancer
37
APC gene mutation
FAP
| AD inheritance
38
MutYH gene mutation
MutYH associated Polyposis
- Phenotypically similar to FAP
- AR inheritance - so may look like de novo FAP
39
STK11 gene mutation
Peutz Jegher Syndrome
| AD inheritance
40
Features of Peutz Jegher Syndrome
- Hamartomatous polyposis ( low malignant potential)
- Lip, buccal, palm pigmentation
- Risk of intussussception/volvulus
- Increased risk of GI and breast cancer
41
MMR gene mutations in Lynch Syndrome
MLH1, MSH2, MSH6, PMS2, EPCAM
42
Amsterdam criteria for Lynch syndrome
3 or more affected relatives w/ CRC
2 or more generations affected
1 or more <50 yo a diagnosis
FAP excluded
43
How to test for MMR mutations
1. MSI testing
2. Immunohistochemistry - absent staining seen if defect
3. Germ line testing
44
SDHB gene mutation
paragangliomas and phaeochromocytoma
45
Neurofibromin 1 gene mutation
neurofibromatoisis type 1
| AD inheritance
46
Neurofibromatoisis type 1 Features
```
2 or more of:
Cafe au lait spots
Neurofibroma/plexiform neurofibroma
Axillary freckling
Lisch modules on irus
Optic glioma
1st degree relative w/ NF
```
47
Merlin gene mutation
neurofibromatoisis type 2
| AD inheritance
48
Neurofibromatoisis type 2 Features
```
Bilateral acoustic schwannoma by age 30 usually
Meningioma/Neurofibroma/Swannoma/Glioma
Polyneuropathy
Cataracts
Cutaneous tumors/plaques
```
49
VHL gene mutation
Von Hippel Lindau Disease
50
Von Hippel Lindau Disease Features
Clear cell renal cancer
Neurological/retinal haemangioblastoma
Phaeochromocytoma
51
Compound heterozygote
Different mutations in each pair of a gene
52
Allelic heterogeneity
The same phenotype can be caused by more than one mutation in a gene (e.g CF)
53
Locus heterogeneity
The same phenotype can be caused by mutations in more than one gene (e.g. tuberous sclerosis)
54
Inheritance of Marfans
AD
55
Inheritance of Tuberous sclerosis
AD
56
Inheritance of vWD
AD
57
Inheritance of Noonan Syndrome
AD
58
Inheritance of Hereditary hemorrhagic telangiectasia
AD
59
Inheritance of acute intermittent porphyria
AD
60
Inheritance of Wilsons Disease
AR
61
Inheritance of Friedrich Ataxia
AR, trinucleotide repeat disorder
62
Inheritance of Haemochromatosis
AR
63
Inheritance of Alpha 1 antitrypsin
AR
64
Inheritance of Phenylketonuria
AR
65
Equation for incidence of a recessive condition
Incidence = (Carrier Freq^2) x4
66
Equation for carrier frequency of a recessive condition
Carrier frequency = square root of (incidence/4)
67
Inheritance of G6PD deficiency
X linked
68
Inheritance of Fabry Disease
X linked
69
Inheritance of Chronic granulomatous disease
X linked
70
Inheritance of Duchenne muscular dystrophy
X linked
71
Inheritance of Rett syndrome
X linked - Dominant
72
Inheritance of Fragile X syndrome
Triplet repeat disorder on X chromosome
| -Worse when maternally transmitted
73
Heteroplasmy
Some mitochondria have a mutation and others don't
74
When can CVS be performed
11-15 weeks
Needle into placenta
1:500 miscarriage risk
75
Role for NIPT
Can be done at 10+ weeks
Assesses for aneuploidy, deletion syndromes, gender
-Fragments of placental DNA extracted from maternal blood
76
CACNA1A gene mutation
Torticollis
77
Features of tuberous sclerosis
```
Ungal/periungal fibroma
Ash leaf macules
Facial angiomas/forehead plaques
Shagreen patch
Retinal nodular hamartomas
Brain - nodules/tubers/astrocytoma - Seizures and ID
Renal angiomyolipoma/cysts
Cardiac rhabdomyoma
LAM - lungs
```
78
Tx option in Tuberous sclerosis
mTOR inhibitors
79
FMR1 gene mutation
Fragile X
| -CGG repeat
80
Features of Friedrich Ataxia
Cerebellum and dorsal root ganglia affected
-Gait and limb ataxia
HOCM
Diabetes
GAA repeat in FXN gene
81
Abnormal Dystrophin gene
Becker muscular dystrophy
| -Deletion/mutation is inframe resulting in a shortened semi functional protein/milder phenotype
82
Absent Dystrophin gene due to deletion usually
DMD
| -Deletion/mutation disrupts the reading frame and therefore no functional protein
83
DMD features
```
Delayed motor milestones
Broad waddling gait, falls
Gower sign - trouble with stairs
Calf pseudohypertrophy (muscle replaced with connective tissue/fat)
Cardiomyopathy
Mild ID
Life expectancy 20s
```
84
Trisomy 21 features
```
ID
Hypotonia
Hearing/Vision
Alz disease
Congenital heart disease: VSD>endocardial cushion defect>PDA>ASD>TOF
Hypothyroid
Leukemia
OSA
```
85
Fragile X features
```
ID, behavioral proglems
Seizures
Mitral Valve prolapse
PRemature ovarian failure
FXTAS
```
86
Karyotype
For detection of:
- Aneuploidy
- Balanced translocation (location of gene)
87
FISH (Fluorescence in situ hybridisation)
Assess for presence of absence of particular DNA sequences on chromosomes
-Balanced rearrangements
88
CGH microarray
Assess gains/loss of DNA content
- For unbalanced changes
- Can detect: microdeletions/duplications and monosomies and trisomies
NOT for Balanced changes
89
SNP Array
```
For copy number neutral variation with genotype abnormalities
Allelic imbalance (uniparental disomy, chimerism)
```
+what CGH microarray does
90
Sanger Sequencing
For single gene mutations
| -Cannot detect deletions/duplications
91
Single gene sequencing
looks at a particular area of interest and gives precise DNA sequencing of targeted gene
-For changes of a single base within a gene
92
Southern blot
For Trinucleotide repeat disorders
Looks at DNA
93
Western Blot
Can be used to look for proteins in trinucleotide repeat disorders like with DMD
94
Whole genome sequencing
o Detects genes and will inform you if there are sequence abnormalities in the gene, but cannot tell you location of the gene or if genes are missing or added
o Helpful for heterogenous conditions (e.g. epilepsy)
o Not good for triplet repeat disorders and deletions
95
miRNA
Post transcriptional regulator that binds to complementary sequences in mRNA
96
siRNA
Small interfering/silencing RNA
Knock down their target RNA
97
Digenic mutation
Two mutations in 2 different genes that code for different proteins that are often structurally or functionally related that lead to a phenotype/disease
98
Wolfram Syndrome
DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness)
AR
Gene: WFS1
99
MELAS
mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes
Mitochondrial disease
```
Stroke like presentation
Seizures
Hearing loss
Muscle weakness
Migraines
```
100
CADASIL
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
NOTCH3 gene mutation on Chromosome 19
CAuse of stroke in young
TIA like Sx and small vessel ischemic strokes
