Chromosome Mutations and Abnormalities - Second Lecture Flashcards

1
Q

What are the three different types of chromosomal abnormalities?

A

Numerical, structural, mutational

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2
Q

What is the result of non-disjunction?

A

Two gametes with disomy (meiosis 1)

1 gamete with disomy - (meiosis 2)

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3
Q

What is trisomy 21 known as?

A

Down’s Syndrome

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4
Q

What is trisomy?

A

The addition of an extra chromosome

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5
Q

What is responsible for 50% of first trimester miscarriages?

A

Trisomy mutations

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6
Q

What are the features of someone with down’s syndrome?

A

Characteristic facial dysmorphologies IQ less than 50 Average life expectancy (50-60 years) Alzheimer’s disease in later life

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7
Q

What is trisomy 13 known as?

A

Patau syndrome Incidence: 1 in 5000 Multiple dysmorphic features and mental retardation

About 5% die within first month, very few survive beyond first year Non-dysjunction (90%), maternal origin Unbalanced Robertsonian translocation (10%)

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8
Q

What is Trisomy 18 known as?

A

(Edwards syndrome) Incidence: 1 in 3000 Severe developmental problems; most patients die within first year, many within first month

Non-disjunction (90%), maternal origin

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9
Q

What is 45, X mutation known as?

A

Turner syndrome Incidence: 1 in 5000 to 1 in 10000 (liveborn) Incidence at conception much greater, about 97% result in spontaneous loss

Females of short stature and infertile Neck webbing and widely spaced nipples Intelligence and lifespan is normal Female because there is no Y chromosome

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10
Q

What is 47,XXY mutation known as?

A

(Klinefelter syndrome) Incidence: 1 in 1000 Tall stature, long limbs Male but infertile, small testes, about 50% gynaecomastia Mild learning difficulties

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11
Q

What are the terms used to describe complete or incomplete retention of DNA during a mutation?

A

Balanced or unbalanced

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12
Q

What is the definition of a balanced translocation?

A

There is still a complete set of DNA between the two chromosomes, if the translocation takes place in a non-critical location, there will be no major effects to the individual

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13
Q

What is meant by reciprocal translocation?

A

Involving breaks in two chromosomes with formation of two new derivative chromosomes

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14
Q

What are the different types of Structural abnormalities?

A

Deletions Insertions Inversions Translocations

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15
Q

What is the effect of unbalanced translocation on the gametes produced?

A

Production of gametes with, partial trisomy and partial monosomy, this will result in offspring with abnormal phenotypes

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16
Q

What are accrocentric chromosomes?

A

One of the arms of the chromosome is very short

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17
Q

What is robertsonian translocation?

A

When the two longer arms of accrocentric chromosomes combine, the short arms are lost and also fuse together

18
Q

What does Robertsonian translocation result in

A

Balanced - normal gametes

Unbalanced - Trisomy and Monosomy

19
Q

What is pericentric inversion?

A

When the inversion takes place over the centromere

20
Q

What is polymorphism?

A

The natural genetic variation within a populaiton

21
Q

What are the different types of genetic mutations?

A

Germline or somatic

Gene disruption /disease-associated

Polymorphism

22
Q

What are the types of non-coding mutations?

A

Coding mutations -

Silent – synonymous e.g. CGA (Arg) to CGC (Arg) (GIVES THE SAME AMINO ACID)

Missense (A MISSENCE MUTATION IS A POINT MUTATION WHICH A SINGLE NUCLEOTIDE CHANGE RESULTS IN A CODON THAT CODES FOR A DIFFERENT AMINO ACID)

Nonsense (CODON FOR AMINO ACID IS CHANGED TO A CODON THAT CODES FOR A CHAIN TERMINATING CODON)

Frameshift – deletion / insertion

23
Q

What are transitions - point mutations?

A

Purine to purine or pyrimidine to pyrimidine

24
Q

What are transversions?

A

Purine to pyrimidine or vice versa

25
Learn Mutation Nomenclature
.
26
What do we use to detect mutations?
Polymerase chain reaction (PCR) Gel electrophoresis Restriction fragment length polymorphism (RFLP) analysis Amplification refractory mutation system (ARMS) DNA sequencing
27
What do we need for PCR?
Sequence information Oligonucleotide primers DNA Nucleotides DNA polymerase
28
What are the three stages of PCR?
Denaturation - 93-95 degrees celcius Anneal - 50-70 93-95 degrees celcius Extend 70-75 93-95 degrees celcius
29
Why is taq polymerase used?
Heat resistant
30
What is used to separate DNA fragments?
Gel electrophoresis
31
What is the charge of DNA?
Negatively charged
32
What does Gel Electrophoresis allow?
Visualisation of DNA fragments
33
What are the advantages of Gel Electrophoresis
Speed Ease of use Sensitive Robust
34
What are the PCR applications?
DNA cloning DNA sequencing In vitro mutagenesis Gene identification Gene expression studies Forensic medicine Typing genetic markers Detection of mutations
35
What are the advantages of Amplification Refractory Mutation System?
Cheap Labelling not required Primer design critical
36
What is the principle of the Amplification Refractory Mutation System?
Specific primers anneal to sample DNA If a mutant primer is used and amplification occurs then the presence of a mutant allele can be conformed If a normal normal primer is used and amplifiacation occurs then the presence of a wild type allele can be confirmed
37
What are the disadvantages of Gel electrophoresis?
Need sequence information Limited amplification size Limited amounts of product Infidelity of DNA replication
38
What is the action of endonuclases?
Recognise specific DNA sequences Always cut DNA at the same site
39
How are endonucleases used to detect mutations?
They cut the DNA at a portion of mutated nucleotide sequence - cutting of the DNA strand only occurs at mutated site, length of travel on the gel therefore gives indication of mutation Two bands gives indication of a carrier
40
What are the Advantages / disadvantages of restriction endonucleases?
Simple Cheap Non-radioactive Requires gel electrophoresis Not always feasible
41
What is used for DNA sequencing?
Chain terminatino method , sanger sequencing, dideoxynucleotides are used
42
What is the Advantages / limitations of DNA sequencing?
Gold standard for mutation detection Automation and high throughput Expensive equipment Poor quality sequence read (First part of sequence (15 to 40 bases) Deterioration after 700-900 bases) Next generation sequencing 18 billion bp in 4 days (about 6 human genomes)