Genetics Flashcards
0
Q
How is DNA always replicated and read?
A
In the 5’ to 3’ direction
1
Q
How do strands of DNA pair up?
A
In an antiparallel fashion
2
Q
What is the DNA sugar backbone composed of?
A
2-deoxyribose (ribose in RNA)
3
Q
What are the bases in DNA and what are the bases in RNA?
A
DNA - ACGT
RNA - ACGU
4
Q
Where is the information in DNA held?
A
In the sequence of the bases which are held on a sugar/phosphate backbone
5
Q
In the DNA molecule what base pairs with what?
A
Thymine with Adenine
Guanine with Cytosine
6
Q
Where are chromosomes found?
A
Within the nucleus
7
Q
What is the DNA strand associated with and what structure is it wound into?
A
Associated with proteins (histones) and is wound into a structure called a chromosome
8
Q
What is the order of the cell cycle starting from G1?
A
G1 GO Synthesis G2 Mitosis
9
Q
What are the three stages in DNA damage and repair?
A
DNA strand breaks
Chemical cross-linking
Mismatched base
10
Q
At what stage of the cell cycle does DNA replication happen?
A
During S phase
11
Q
What does mitosis start with and finish with?
A
Starts with one diploid parent cell
Ends with two identical diploid daughter cells
12
Q
What does meiosis start with and finish with?
A
Starts with one diploid parent
Ends with 4 haploid daughter cells
13
Q
Does crossing over occur in meiosis?
A
Yes i.e. genes segregate independently, even if on the same chromosome
14
Q
Does meiosis occur in gamete formation?
A
Yes
15
Q
What 3 changes does Ribonucleic acid (RNA) have compared to DNA?
A
- Single stranded
- Ribose in backbone not deoxyribose
- Uracil is used instead of Thymine
16
Q
What are promotor, exon, intron, exon and stop all in?
A
DNA
17
Q
What is exon, exon, stop in?
A
mRNA
18
Q
What 4 things determine the amount of protein produced?
A
- Rate of transcription (manufacture of Pre-mRNA)
- Rate of splicing to mRNA
- Half life of mRNA
- Rate of processing of polypeptide
19
Q
What does DNA get transcribed into?
A
pre-mRNA
20
Q
What does pre-mRNA get spliced into?
A
mRNA
21
Q
What is mRNA translated into?
A
Protein
22
Q
What can 3 bases encode?
A
1 amino acid or a stop
23
Q
What two things allow the genome to vary in individuals?
A
Polymorphisms and mutations
24
What 2 sequence variations are there within a gene?
Changes in the promotor sequence
| Changes in the exon sequence (one that change an amino acid, sequence changes that do not)
25
What two sequence changes in the DNA between genes are there?
Single nucleotide polymorphisms (SNPs)
| Larger deletions or duplications
26
Give the definition of polymorphisms
Any variation in the human genome that does not cause a disease in its own right. It may however, predispose to a common disease
27
What is a mutation?
A gene change that causes a genetic disorder
Any heritable change in the human genome
28
Classical genetic diseases occur because?
One mutation is sufficient to cause disease e.g. achondroplasia, muscular dystrophy)
29
What does multifactorial diseases mean?
Multiple polymorphisms cause a risk of disease
30
What is the key equation for clinical genetics?
Disease = gene + environment
31
Before DNA is transcribed what has to happen?
It has to be unpacked
32
What three things allow a chromosome to be recognised?
1. Banding pattern with specific stains
2. Length
3. Position of the chromosome
33
What rearrangement has occured if all the chromosomal material is still present?
Balanced
34
What chromosome rearrangement would have occured if there is extra or missing chromosomal material?
Unbalanced
35
Define aneuploidy
Whole extra or missing chromosome
36
Define translocation
Rearrangement of chromosomes
37
What disease occurs: trisomy 21?
Down syndrome - extra chromosome 21 (47 XY +21)
38
What is Robertsonian translocation?
Two acrocentric chromosomes stuck end to end
39
What can occur with a trisomy 14?
Miscarriage
40
What will increase the recurrence of down syndrome?
If the primary trisomy 21 is caused by robertsonian translocation
41
What disease is caused by trisomy 18?
Edward syndrome
42
What disease is associated with 45 X?
Turners syndrome
43
What disease is associated with 47 XXY?
Klinefelters syndrome
44
What is FISH?
Fluoresence in Situ Hybridisation
45
What do chromosomes carry?
Genes
46
What is the male chromosome complement?
46 XY
47
What is the female chromosome complement?
46 XX
48
What 2 things can unbalanced rearrangements cause?
Mutliple malformations
| Miscarriage
49
What is the first line chromosome test?
Array CGH
50
What 2 diseases is Gonadal Mosaicism most common in?
1. Duchenne Muscular Dystrophy
| 2. Osteogenesis Imperfecta
51
What causes a recurrence risk for autosomal dominant conditions even if the parent is unaffected?
Gonadal Mosaicism
52
Chromosome changes indicate treatment: Her2 amplification?
Monoclonal antibody: Trastuzamab
53
Chromosome changes indicate treatment: Philadelphia chromosome?
Tyrosine Kinase Inhibitor: Imatinib
54
What genetic change can contribute towards cancer?
Somatic mosaicism for a chromosomal abnormaility
55
What is penetrance?
The liklihood of having a disease if you have a gene mutation. 100% prevelance means you will always get the disease if you have the mutation.
56
What name is given to diseases that segregate in families in the manner predicted by Mendel's Law?
Mendelian disorders: essentailly a disease that is predominantly caused by a change in a single gene (high penetrance)
57
What are chromosome aneuplodies?
Extra or missing chromosomes
58
What two methods are in place to find genetic faults?
1. PCR and conventional (Sanger) sequencing
| 2. Next Generation Sequencing (NGS)
59
Give an example of focused genetic testing?
PCR
60
What is reduced or abolished in a DNA promotor mutation?
Reduced or no transcription
| Reduced or no protein
61
What occurs if splice consensus is altered?
An mRNA decay in translation
| Abnormal or absent protein
62
What occurs if a base change makes a new stop?
mRNA decay at translation
| Short or absent protein
63
What occurs if a base change alters amino acid sequence?
Different or non-functioning protein
64
What are the 7 types of mutations in DNA sequences?
1. Wild type
2. Stop
3. Missense
4. Insertion
5. Deletion (out of frame)
6. Deletion (in frame)
7. Triplet expansion
65
What do promotor and splice site sequence changes do?
Stop transcription or cause abnormal splicing
66
What can a trinucleotide repeat expansion cause?
Replication of a trinucleotide
67
What is genetic heterogeneity?
The same disease might be caused by mutations in one of several genes
68
What are the 4 types of Mendelian Inheritance?
Autosomal dominant
Autosomal recessive
X-linked
(Mitochondrial)
69
With an autosomal dominant mutation what is the risk of an affected child if the parents are affected?
50%
70
What are the 4 types of autosomal dominant mutations?
```
Wild type
Missense
Deletion (in frame)
Premature stop
Deletion (frameshift)
```
71
In an autosomal recessive mutation, what do you need to cause disease?
2 faulty copes of the gene
72
In an autosomal recessive mutation what is the risk of an affected child if the parents are carriers?
25%
73
Give an example of an autosomal recessive disease?
Phenylketonuria
74
In an X linked recessive disease where does the gene fault lie?
On the X chromosome
75
In an X-linked recessive inheritance: for a female carrier what percentage of male children will be affected and what percentage of female children will be carriers?
50%
| 50%
76
In an X-linked recessive inheritance: if an infected male has children what percentage of them will be normal and what will all the female chilren be?
All male children will be normal
| All female children will be carriers
77
In female cells how many x chromosomes are active?
one
78
What gene is essential for X inactivation?
the XIST gene at Xq13
79
Give one mechanism of X inactivation
Methylation
80
Give two types of variation?
Single Nucleotide Polymorphisms
| Copy Number Variation
81
What variation is an alteration in the DNA sequence?
A single nucleotide polymorphism
82
What are copy number variations?
Extra or missing stretches of DNA
83
Define expression
Variation in disease severity if you have the mutation
84
What are the 4 M's of Non-Mendelian Inheritance?
Multifactorial
iMprinting
Mitochonddrial
Mosaicism
85
What disorder has high penetrance and small environmental contribution?
Mendelian disorders
86
What disease is a genetic change as a risk factors and penetrance for any one mutation is low?
Multifactorial disease
87
What to methods are there for working out if a disease phenotype has a genetic contribution to its causation?
Recurrence risk in siblings
| Twin studies
88
What is Filaggrin deficiency?
A null allele polymorphism
| Strongly associated with eczema
89
What type of disorder does epigenetic modification of DNA come under?
Non-Mendelian inheritance patterns
90
What bases just methylation usually occur on?
Cytosine bases
91
What leads to the modification of histones (including de-acetylation) and represses transcription?
DNA methylation
92
What mutation causes RETT syndrome?
Mutation in the MECP2 gene on Xq28.13
93
Give 2 features of Angelman syndrome
```
Developmental delay
Intellectual disability
Ataxia
Epilepsy
Happy demeanor
Frequent laughing and smiling
```
94
What working copy of gene do you need to avoid Angelman's syndrome?
UBE3A
95
What chromosome is UBE3A on?
15
96
What is special about the copy of UBE3A from your father?
It is methylated
97
What is imprinting?
Variation in gene expression depending on which parent you inherit the gene from
98
What is imprinting controlled by?
Methylation
99
What does methyl cytosine mutate easily into?
Thymine
100
Where else is DNA kept?
Mitochondrial DNA
101
What mutations occur in mitochondrial DNA?
Point mutations and deletions occur
102
What is heteroplasmy?
Different daughter cells contain different proportions of mutant mitochondria
103
Give 2 symptoms of mitochondrial disease?
```
Myopathy
Diabetes
Deafness
Optic atrophy
Stroke like episodes
Encephalitis
```
104
How is mitochondrial inheritance transmitted?
Maternal transmission only
105
What 4 genes are involved in cancer?
Oncogenes - switch these on for cell division
Tumour supressors - switch these on to stop cell division
DNA repair genes - repair DNA damage
Drug metabolism - genes that metabolise carcinogens
106
What type of inheritance does retinoblastoma have?
Autosomal dominant
107
What 3 methods are there for activating oncogenes?
Duplication of the gene
Activation of the gene promotor
Change in amino acid sequence
108
What is Imatinib (Glivec) a specific inhibitor of?
ABL oncogene
109
What occurs in interphase of the cell cycle?
The cell grows, accumulating nutrients needed for mitosis and duplicating its DNA
110
What happens during the mitotic phase of the cell cycle?
The cell splits intself into two distinct cells, often called daughter cells
111
In G1 of the cell cycle what happens?
The cell makes new proteins
112
If the cell is not ready to move onto S phase what happens?
It enters G0 and carries out its normal acitivity
113
What occurs in synthesis of the cell cycle?
DNA replication
114
What occurs in G2 phase?
The cell prepares to divide
115
Depending on the location of the centromere, what can chromosomes be classified as?
Submetacentric
Metacentric
Acrocentric
116
What does splicing consist of?
The removal of introns
117
What does transcription involve?
The synthesis of a single strand of mRNA by RNA polymerase
118
Where does splicing take place?
In the nucleus
119
What is translation?
The synthesis of a protein from a mRNA template
120
Where does protein synthesis occur?
In ribosomes
121
What are ribosomes made up of?
Ribosomal RNA and proteins
122
When is translation terminated?
When the ribosome comes across one of the three base combinations known as termination codons (or stop codons) at hte end of the gene: UAA, UAG, UGA
