Genetics. Flashcards
0
Q
What direction is DNA replicated and read?
A
The 5’ end to the 3’ end.
1
Q
How do we describe the way DNA strands line up?
A
The pair up in an anti parallel fashion.
2
Q
What is at the end of the 5’ end of a DNA strip?
A
A phosphate.
3
Q
What is at the 3’ end of a DNA strip?
A
An OH hydroxyl group.
4
Q
Describe DNA.
A
Information molecule, due to sequence of bases. Two strands of DNA bind in an anti parallel form. Sugar is 2-deoxyribose and bases are ACGT
5
Q
What are the bases of DNA and how do they pair up?
A
Adenine, guanine, cytosine and thymine. C-G and A-T.
6
Q
What are the bases of rNA and how do they pair up?
A
Adenine, guanine, cytosine and uracil.
C-G and A-U.
7
Q
What is a chromosome?
A
String of nucleotides wound around proteins e.g histones.
8
Q
What is the cell cycle?
A
M - mitosis, G1 - gap 1 which can either lead to G0 (cell resting and just being a cell), or S - synthesis (DNA synthesis) and then G2 - gap, leading back to meiosis.
9
Q
What happens during S phase of the cell cycle?
A
DNA replication. DNA can be damaged during this time. Repair mechanisms exist, but defects in these cause disease.
10
Q
What happens during mitosis?
A
One diploid parent creates two diploid daughters.
11
Q
What happens at meiosis?
A
One diploid parent becomes 4 haploid daughter cells. Crossing over occurs here.
12
Q
What do diploid and haploid mean?
A
Diploid= Two of each chromosome to each cell. Haploid = one of each chromosome in each cell.
13
Q
What is a promoter in genetics?
A
The region of a gene that determines where RNA polymerase binds and initiates transcription.
14
Q
What is an intron?
A
A section of Gene that is transcribed into the primary RNA transcript but is spliced out during exon splicing.
15
Q
What is an exon?
A
Segment of a gene that remains after splicing the RNA transcript.
16
Q
What are the main steps in going from DNA to a protein?x
A
DNA is transcripts to make pre mRNA. Pre mRNA is spliced to make mRNA. mRNA is translated to make protein.
17
Q
What allows us to be able to code for proteins even if mutation occurs?
A
Different base orders can code for the same amino acid.
18
Q
What factors affect the amount of a protein produced?
A
Rate of transcription, rate of splicing, half life of mRNA and the rate of processing of a polypeptide.
19
Q
What is a polymorphism?
A
Any variation in the human genome that has a population frequency of more than 1% or any variation in the human genome that does not cause a disease in its own right, although it may predispose to one.
20
Q
What is a mutation?
A
A gene that causes a genetic disorder or any heritable change in the human genome.
21
Q
What is a classical genetic disease?
A
One mutation that is sufficient to cause a disease e.g. Muscular dystrophy.
22
Q
What is a multi factorial disease?
A
Multiple polymorphism that cause the risk of a disease.
23
Q
What causes genetic variation?
A
Crossing over at meiosis making each human genome slightly different.
24
What is the key equation for geneticists?
```
Disease = gene + environment.
Phenotype = genotype + environment.
```
25
How many chromosomes do we have?
46 in 23 pairs. 22 and one pair of sex chromosomes.
26
What is a karyotype?
The picture of the chromosomes lines up in their pairs.
27
How do we recognise different chromosomes?
The banding pattern with specific stains, the length and the position of the centromere.
28
Describe what a chromosome looks like?
A centromere in the middle with a long (q) and short (p) arm coming out of either side. They have a telomere in each end.
29
What is a telomere?
Sequence of repeating nucleotides on each end of a chromosome that acts as a protective cap.
30
What is an acrocentric chromosome?
A chromosome with the centromere very near one end e.g. 14, 15 and Y. The short arm doesn't really matter.
31
What is balanced chromosome rearrangement?
All the chromosome material is present.
32
What are the two types of chromosome rearrangements that can cause disease?
Balanced and unbalanced.
33
What is unbalanced chromosome rearrangement?
Extra or missing pieces of chromosomal material. Usually one or three copies of the same genome.
34
What is aneuploidy?
Whole extra or missing chromosome.
35
What is translocation?
Rearrangement of chromosomes.
36
What are 5 different kinds of mutation that can cause disease?
Aneuploidy, translocation, insertion, deletion and microdeletion.
37
What is Down's syndrome?
Trisomy 21 e.g 3 different chromosome 21's. Therefore the chromosome complement would be 47 e.g. 47 XY + 21.
38
What is a robertsonian translocation?
Two acrocentric chromosomes stuck end to end. E.g. R(14:21)
39
What is a risk of robertsonian translocation and what can this cause?
Increased risk of trisomy in pregnancy. E.g. The mother has two of each chromosome with one of them stuck together (e.g. 14 and 21, giving the appearance of three chromosome in total). Father has two of each. Child may have a normal inheritance, a balanced translocation the same as the mother. Trisomy 14 (miscarriage) or trisomy 21.
40
What is the recurrence rate of having another Down syndrome child if you already have 1?
1% if the child has primary trisomy 21. Higher if it is caused by a robertsonian translocation.
41
What is trisomy 18?
E.g. 47 XY + 18. Gives Edwards syndrome.
42
What is 45x?
Turners syndrome.
43
What is a feature of X chromosome aneuploidy vs. Y chromosome aneuploidy and why?
X is better tolerated due to X inactivation. The X has all the genes needed and so the Y isn't really required.
44
What is 47XXX?
Triple X.
45
What is 47 XXY?
Klinefelter syndrome.
46
What is reciprocal translocation? And what can it cause?
Where 2 parts of separate chromosomes have broken off and switched over. It can result in: normal, a balanced translocation, or a partial trisomy partnered with a monosomy (unbalanced).
47
What are the 4 types of meiotic segregation modes for reciprocal translocations?
Alternate, adjacent 1, adjacent 2 and 3:1.
48
What does alternate segregation result in?
Either normal or a balanced abnormality.
49
What do adjacent 1 and 2 segregation a result in?
Unbalanced abnormalities.
50
What are the reproductive risks of reciprocal translocations?
For most translocations half of pregnancy a will be normal or balanced. The other half will be unbalanced. If this is a large portion, miscarriage will occur. In small portions they will have a dysmorphic delayed child.
51
What are some examples of gonadal mosaicism and its outcomes?
Commoner in diseases like muscular dystrophy and osteogenesis imperfecta. Causes risk for autosomal dominant conditions even if the patient is unaffected.
52
What is a pedigree?
Basically a family tree, showing whether mutations are new or not.
53
What questions do we ask to discern whether a mutation is a polymorphism or a disease causing mutation?
Is it de-novo? Has it been reported before? In the same phenotype it may be causative. As a polymorphism it's not causative. What gene does it delete?
54
What is mosaicism?
When an organism has come from one zygote but has two different genotypes. Everyone has somatic mosaicism.
55
What is FISH?
Fluorescent in situ hybridisation. Probes are created that match parts of the gene, dyed and allowed to attach. Can show scientists if there are too many of the cancer creating HER2 gene present etc.
56
What is PCR?
Polymerase chain reaction. 2 primers are custom made to attach to two segments of gene. DNA polymerase is then allowed to attach and this copies the segment in between the two primers. Can make millions of copies of the part of the genome required. Can also do full genome sequencing with PCR, if an allele of the gene has a mutation then the PCR fragment will not attach. Copies are therefore not made and this can be seen in a tracing made after PCR.
57
What is array CGH?
Array comparative genome hybridization. Patient and control DNA are dyed and mixed. Put on a slide with thousands of probes, one for each part of the genome. DNA migrates and attach. Computer analyses the colours, too much of patients = extra chromosomal material, too little = missing material.
58
What genetic changes can contribute to cancer?
Mutations happen at every division, about 10-6 times per division. Cancer can happen if mutations switch of tumour suppressors or activate an oncogene.
59
What is the Philadelphia chromosome?
Specifics chromosome translocation that causes leukaemia. Part moves from 22 to 19.
60
What treatment do we give for HER 2 amplification?
The monoclonal antibody Trastuzamab.
61
What treatment do we give to people with the Philadelphia gene?
Tyrosine kinase inhibitor - Imatinib.
62
What is penetrance?
The likelihood of getting a disease if you have a gene mutation. 100% = definitely.
63
What are Mendelian disorders?
Diseases that segregate in families in the manner predicted by Mendels laws. Usually one by a single gene. Mendelian inheritance disorders have high penetrance.
64
What is a wild type?
The phenotype of a particular form of a species as it occurs in nature.
65
What is a promoter or splice site sequence mutation and what effect does it have?
The splicing of a protein will be in the wrong place as the intron has mutated. Or the transcription will start in the wrong place. This results in a stopped transcription or altered splicing.
66
How many base pairs encode an amino acid?
3 e.g. One codon.
67
What is the result of a base change mutation causing an amino acid change?
Change in protein sequence, not every base change causes disease, it may or may or not reduce protein function and some may even make it faster.
68
What is a missense mutation?
A base change.
69
What are the two types of deletions we can get?
In frame or out of frame (frameshift).
70
What is a trinucleotide repeat expansion?
One codon being replicated and repeated e.g. Cat cat cat.
71
What is genetic heterogeneity?
The same disease can be caused by mutations on several genes.
72
What are advantages and disadvantages of genome wide testing?
Costly, risk of drowning in data due to millions of polymorphisms and may have incidental findings to worry about. It means you are less likely to miss something though.
73
What are the advantages and disadvantages of targeted gene testing?
Cheaper and lower risk of incidental findings.
| But you need to know where to look.
74
What are the features of Medelian inheritance?
Can be autosomal dominant or recessive. X linked or mitochondrial.
75
What are the features of autosomal dominant inheritance?
Disease is seen in all generations, 50% risk of affected child if there is an effected parent. Disease severity can be variable. Males and females are equally likely to be affected.
76
What is haploinsufficiency?
When having one working copy of a gene is not enough.
77
What do we call it when an abnormal protein interferes with a normal one?
Dominant negative.
78
What is a gain of function mutation?
When a mutation activates a gene.
79
What are the symbols we use for a pedigree?
```
Make = square.
Female = circle.
Affected = coloured in.
Triangle = miscarriage.
Scored through = dead.
```
80
What are the features of autosomal recessive inheritance?
2 copies of faulty gene. Often only one generation affected. 1 in 4 risk of an affected child of the patient is a carrier. Mutations usually cause loss of function.
81
What are the features of x-linked inheritance?
The gene fault lies on the x-chromosome. Females have the mutation but don't show major features of the disease.
for a female carrier: half of male children will be affected and half of females carriers.
For a male affected: all male children will be normal, all females will be carriers.
82
What is X inactivation?
Only one chromosome active in females so other allele not needed.
83
What is a mutation?
A gene change that causes a genetic disorder.
| Or any heritable change in the human genome.
84
What is an SnP?
Single nucleotide polymorphism, occur roughly every 100 to 300 bps.
85
What happens if we have a promoter polymorphism?
Gives less transcription and reduced mRNA.
| Translation will give less protein.
86
What are copy number variations?
Extra or missing stretches of DNA.
87
What do we observe with Mendelian disorders?
High penetrate and a small environmental contribution.
88
What penetrate risk do we have in multi factorial disease?
Penetrate for any one mutation is low but can have a cumulative defect.
89
What are the four Ms of non-Mendelian inheritance?
Multifactoral
iMprinting.
Mitochondrial
Mosaicism
90
How do we know if there is a genetic component to a disease?
More common in relatives.
Increased risk in siblings.
Doesn't take shared environment into account tho.
91
What does P
There is a one in 20 possibility that the data you see has happened by chance.
92
What do 5A/6A promoter polymorphisms in MMP3 cause?
Having a 5A/5A genotype gives a greater risk of aortic aneurysms.
Have in one 5A gives a slightly increased chance.
93
What Filaggrin deficiency?
A null allele polymorphism strongly associated with eczema.
94
What is DNA methylation and what does it do?
Interaction with protein histones, usually occurring at cytosine bases before guanine bases. It prevents transcription.
95
What is the clinical importance of methylation?
Abnormalities can cause genetic disease.
Methylation can silence cancer genes.
It provides a mechanism to allow environment to affect gene expression e.g. Starvation during pregnancy affects the foetus.
96
What is imprinting?
Differences in gene expression dependent on whether is paternal or maternal.
97
What is herteroplasmy?
Different daughter cells contain different proportions of mutant mitochondria.
98
What are some symptoms of mitochondrial disease?
```
Myopathy
Diabetes
Eagles
Optic atrophy
Stroke like episodes
Encephalitis
```
99
What is retinoblastoma from a genetic perspective?
Autosomal dominant mutation with variable penetrate.
| Is mutation of a tumour suppressor gene and both copies must be lost to allow for tumour growth.
100
What is the two hut hypothesis of genetic mutations?
Have one inherited mutation and then an acquired one causing disease.
101
What are polymorphisms?
Any variation in the human genome that does not cause disease in its own right.
