Molecular genetics Flashcards
1
Q
How many barr bodies in trisomy X?
A
2
2
Q
What is a Barr body?
A
When X chromosome is inactivated
3
Q
How does X inactivation occur?
A
DNA methylation
4
Q
What is mutation in SHANK3 associated with?
A
Autism
5
Q
Mutation in KISS1 gene
A
Kallmann syndrome - hypogonadotrophic hypogonadism
6
Q
What is the heritability of bipolar?
A
75-85%
7
Q
What are the purines?
A
Adenine and guanine
8
Q
What are the pyrimidines?
A
Thymine and cytosine
9
Q
What are the possible base pairs of DNA?
A
TA
AT
GC
CG
10
Q
What does genetic abnormality of Progranulin cause?
A
Frontotemporal dementia
11
Q
Where is progranulin gene found?
A
17q21
12
Q
What is locus heterogeneity?
A
Same disease phenotype caused by mutations at different loci
13
Q
What is a cloning vector?
A
Small piece of DNA into which foreign DNA fragment can be inserted
14
Q
What is polymorphism?
A
Natural variations in a gene, DNA sequence or chromosome that have no adverse impact on the individual & occur with fairly high frequency in the general population
15
Q
Which gene encodes for serotonin transporter?
A
SL6CA4
16
Q
Where is SL6CA4 found?
A
Chromosome 17 - 17q11
17
Q
Where would you find COMT?
A
22q11
18
Q
How is fragile X inherited?
A
X-linked
19
Q
Which trinucleotide repeat is responsible for Fragile X?
A
CGG
20
Q
What is heritibility?
A
Proportion of variation of an observed feature that is due to genetic factors
21
Q
What are the 3 steps of PCR?
A
- DS DNA denatured by heat into single strand then annealed by cooling
- DNA polymerase used to extend primers in opposite directions. After 1 cycle there are 2 copies of DNA, after 2 cycles there are 4 copies.
- Cycling is set to produce the necessary number of amplifications
22
Q
What is the lifetime risk of unipolar depression in a first degree family member with bipolar disorder?
A
10-20% (2-3x greater than general population)
23
Q
What % of the human genome is considered to be active with coding sequences?
A
2%
24
Q
Where is mitochondrial DNA inherited from?
A
Ovum
25
How many autosomes in a human cell?
44
26
What is the law of segregation?
For any particular trait, the pair of alleles of each parent separate and only one allele passes from each parent to an offspring
27
Which nuclear component undergoes splicing?
Intron
28
What is an intron?
Any nucleotide sequence within a gene that is removed by RNA splicing to generate final mature RNA product of gene
29
Gene associated with late onset dementia
APO E on chromosome 19
30
What is an inframe mutation?
Changes happening in multiple of 3 bases with no disturbances to the actual reading frame
31
What is epistasis?
Gene-gene interaction between different alleles of different genes
32
What is alternate splicing?
Where one gene gives rise to more than one protein
33
LOD score for statistical evidence of linkage
Over 3
34
LOD score evidence something not linked
-2 or less
35
Maternal inheritance of Huntington's effect on disease severity
More severe disease
36
3 stop codons
UAA
UGA
UAG
37
Southern blot test
Visualises restriction fragment length polymorphisms
38
How are genetic distances expressed?
centiMorgans
39
What is one centiMorgan equivalent to?
1% recombination frequency between two loci
| 1,000,000 base pairs of DNA
40
Difference between missense and nonsense mutation
Missense - new mutant codon specifies a different amino acid with variable effects on final protein product
Nonsense - new codon codes for stop code
41
Which cells remain in G0 stage indefinitely?
Liver cells
| Neurons
42
How is Noonan's inherited?
Autosomal dominant
43
What is a Robertsonian translocation?
Where chromosomes break at their centromeres and the 2 long arms fuse to form a metacentric chromosome
Non-reciprocal translocation involving 2 homologous pairs or non-homologous chromosomes
44
Which enzyme mediates the binding of tRNA with amino acids?
Aminoacyl synthetase
45
Risk of AD in patient who is heterozygous for APOE4 compared to those with no APOE4 allele
3x higher
| For homozygous 15x
46
How is Rett's inherited?
X-linked dominant
47
Best technique to detect large sequence of DNA
South blotting
48
Role of RNA polymerase
Synthesis of RNA from a DNA template
49
Features of Argyll-Roberston Pupil
Will accommodate but light reflex absent
50
Deletion of which chromosome causes Prader-Willi?
Paternal 15q11 q13
51
What method can be used to detect abnormal trinucleotide repeats?
PCR
52
What phenomena explains most epigenetic variations?
DNA methylation and histone modifications
53
Which form of inheritance might skip a generation and then reappear?
Autosomal recessive
54
Which gene is mutated in PKU?
Phenylalanine hydroxylase
55
How are monozygotic twins formed?
When an embryo is cleaved during early development
56
How are dizygotic twins formed?
Fertilisation of 2 different ova by 2 different sperm
57
What % of genes do dizygotic twins share?
50%
58
What is the lifetime risk of developing schizophrenia in a sibling of a patient?
10%
59
CADASIL is associated in a mutation in which gene?
NOTCH3
60
What is CADASIL?
Cerebral Autosomal Dominant Ateriopathy with Subcortical Infarcts and Leukoencephalopathy
61
What is transcription?
Using DNA template to form RNA
62
What is replication?
Forming DNA from DNA
63
What is translation?
Using RNA template to form protein
64
What are the polypeptide coding sequences in DNA called?
Exons
65
What are non-coding sequences in DNA?
Introns
66
What are the 3 types of sequences introns contain?
Satellite - large sequence of repeats
Minisatellite
Microsatellite - single, di or tri nucleotide repeats
67
What happens to all introns in mRNA before starting protein synthesis?
They are removed
68
Where does translation take place?
Cytoplasm aided by ribosomes
69
3 steps of translation
1. Initiation
2. Elongation
3. Termination
70
Gene problem Smith-Magenis
17q11.2
71
Features of Smith Magenis syndrome
Self hugging
Pulling off nails
Inserting foreign objects into orifies
72
Williams gene problem
17q11 microdeletion
73
Cri-du-chat syndrome gene
Deletion of chromosome 5p
74
What is incomplete penetrance?
Patients have dominant disorder but it does not manifest itself clinically
75
How might a female manifest a X-linked recessive disorder?
Unfavourable lyonization - deactivation of most normal alleles
76
How is tuberous sclerosis inherited?
Autosomal dominant
77
Gene and features of TS
9q34
| Adenoma sebaceum, cysts, brain hamartomas
78
Treacher collins features
Autosomal dominant
Maxilla-mandibular hypoplasia
Down slanting palpebrae
Mild to moderate MR
79
Treacher collin gene
5q31
80
Apert syndrome gene
10q
81
Apert syndrome features
```
Autosomal dominant
Craniosynostosis
Shallow orbits
Trapezoid mouth
Mitten hands
```
82
Noonan syndrome gene
Chr 12
83
Noonan syndrome features
Mild MR
Short stature
Webbed neck
Pulmonary stenosis
84
How is Hurler syndrome inherited?
Autosomal recessive
85
Hurler syndrome gene
4p16
86
Hurler syndrome features
Deteriorating IQ after 2 years
Coarse facies
Clouded cornea
Joint stiffness
87
Lesh-Nyhan gene
Xq26-27
88
How is Lesch-Nyhan inherited?
Autosomal recessive
89
Best known example of X-linked dominant disease
Vitamin-D resistant rickets
90
Fragile X trinucleotide repeat
CGG - proximal to FMR1 gene
91
Friedreich Ataxia trinucleotide repeat
gAA
92
Huntington chorea trinucleotide repeat
CAG
93
Myotonic dystrophy trinucleotide repeat
CTG
94
Southern blotting
Detection of specific sequence in DNA
95
Western blotting
Detection of specific protein after electrophoresis
96
Northern blotting
Detection of specific RNA sequence after electrophoresis
97
What is FISH used for?
Localise specific DNA sequences on a chromosome
98
Heritability estimate Schizophrenia
80
99
Heritability estimate BPD
Over 80
100
Heritability estimate major depression
40
101
Heritability estimate anxiety
30
102
Heratibility estimate panic
40
103
Heratibility estimate alcoholism
60
104
Big 5 personality traits and their heratibility
```
Openness - 57%
Extraversion - 54%
Conscientiousness - 49%
Neuroticism - 48%
Agreeableness - 42%
```
105
What is Hardy-Weinberg equilibrium?
In the absence of mutation, non-random mating, selection and genetic drift, the genetic constitution of the population remains the same from one generation to the next
106
What is alllelic heterogeneity?
Same disease phenotype from different mutations at same loci (e.g. CF - 600 mutations at chromosome 7 resulting in same disease)
107
What is pleiotropy?
Single disease causing mutation affects multiple organ systems e.g. Marfan's
108
MZ vs DZ concordance of male alcoholism
41% vs 22%
109
MZ vs DZ concordance of Bulimia
23% vs 9%
110
MZ vs DZ concordance Autism
64% vs 9%
111
Tourette's MV vs DV concordance
53% vs 8%
112
Female alcoholism MZ vs DZ concordance
34% vs 31%
113
Genes implicated in Schizophrenia (6)
```
DISC1
COMT
NRG1 (neuregulin)
DTNBP1 (dysbindin)
DAAO
RGS4
```
114
Where is DISC1 gene
1q42
115
Most frequent personality disorder in relatives of patients with Schizophrenia?
Schizotypal
116
General population risk of schizophrenia
1%
117
First cousins risk of Schizophrenia
2%
118
Uncles/Aunts risk of Schizophrenia
2%
119
Nephews/Nieces risk of Schizophrenia
4%
120
Grandchildren risk of Schizophrenia
5%
121
Half siblings risk of Schizophrenia
6%
122
Parents risk of Schizophrenia
6%
123
Siblings risk of Schizophrenia
9%
124
Children risk of Schizophrenia
13%
125
Identical twins risk of Schizophrenia
48%
126
Fraternal twins risk of schizophrenia
17%
127
Risk of BAD in population, 1st degree rel & monozygotic twins
pop - 0.5-1.5%
1st - 5-10%
mono - 40-70%
128
Lifetime risk of unipolar disorder in general pop, 1st degree rel and monozygotic twin
pop - 5-10%
1st - 10-20%
Mono - 15-25%
129
Which genes are suspected in BAD?
COMT
BDNF
DAO G72/G30
130
Genes in early onset dementia and their chromosome location
Presenilin 1 - chromosome 14
Presenilin 2 - chromosome 1
APP - chromosome 21
131
Effect on APOE2 on AD
Protective
132
Effect of APOE3 on AD
Neutral
133
Effect of APOE4 on AD
Increases risk
134
Where is APOE located?
Chromosome 19
135
Which gene is associated with late onset dementia?
APOE
136
Genes associated with Familial Frontotemporal Dementia
Progranulin
| MAPT
137
Genes potentially associated with Parkinson's disease
SNCA - chromosome 4 - alpha-synuclein - dominant
| Parkin - recessive inheritance
138
Recurrence rate in siblings of autism inc. RR
2-8%
| 50x RR
139
Heritability of ADHD
70-80%
140
Genes linked to alcoholism
GABRA2 - chromosome 4
ADH4 - early onset regular drinking
DRD2
