Chromosome Mutations and Abnormalities - Second Lecture Flashcards Preview

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Flashcards in Chromosome Mutations and Abnormalities - Second Lecture Deck (42):
1

What are the three different types of chromosomal abnormalities?

Numerical, structural, mutational

2

What is the result of non-disjunction?

Two gametes with disomy (meiosis 1)

1 gamete with disomy - (meiosis 2)

3

What is trisomy 21 known as?

Down's Syndrome

4

What is trisomy?

The addition of an extra chromosome

5

What is responsible for 50% of first trimester miscarriages?

Trisomy mutations

6

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

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

7

What is trisomy 13 known as?

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%)

 

 

8

What is Trisomy 18 known as?

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

Non-disjunction (90%), maternal origin

9

What is 45, X mutation known as?

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

10

What is 47,XXY mutation known as?

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

11

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

Balanced or unbalanced

12

What is the definition of a balanced translocation?

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

13

What is meant by reciprocal translocation?

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

14

What are the different types of Structural abnormalities?

Deletions Insertions Inversions Translocations

15

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

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

16

What are accrocentric chromosomes?

One of the arms of the chromosome is very short

17

What is robertsonian translocation?

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

18

What does Robertsonian translocation result in

Balanced - normal gametes

Unbalanced - Trisomy and Monosomy

19

What is pericentric inversion?

When the inversion takes place over the centromere

20

What is polymorphism?

The natural genetic variation within a populaiton

21

What are the different types of genetic mutations?

Germline or somatic

Gene disruption /disease-associated

Polymorphism 

22

What are the types of non-coding mutations?

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

What are transitions - point mutations?

Purine to purine or pyrimidine to pyrimidine

24

What are transversions?

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)