Chromosome Mutations + Abnormalities Flashcards
<p>What are the three different types of chromosomal abnormalities?</p>
<p>Numerical, structural, mutational</p>
<p>What is the result of non-disjunction?</p>
<p>Two gametes with disomy (meiosis 1)</p>
<p>1 gamete with disomy - (meiosis 2)</p>
<p>What is trisomy 21 known as?</p>
<p>Down's Syndrome</p>
<p>What is trisomy?</p>
<p>The addition of an extra chromosome</p>
<p>What is responsible for 50% of first trimester miscarriages?</p>
<p>Trisomy mutations</p>
<p>What are the features of someone with down's syndrome?</p>
<p>Characteristic facial dysmorphologies
IQ less than 50
Average life expectancy (50-60 years)
Alzheimer’s disease in later life</p>
<p>What is trisomy 13 known as?</p>
<p>Patau syndrome Incidence: 1 in 5000
Multiple dysmorphic features and mental retardation</p>
<p>About 5% die within first month, very few survive beyond first year
Non-dysjunction (90%), maternal origin
Unbalanced Robertsonian translocation (10%)</p>
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<p>What is Trisomy 18 known as?</p>
<p>(Edwards syndrome) Incidence: 1 in 3000 Severe developmental problems; most patients die within first year, many within first month</p>
<p>Non-disjunction (90%), maternal origin</p>
<p>What is 45, X mutation known as?</p>
<p>Turner syndrome Incidence: 1 in 5000 to 1 in 10000 (liveborn)
Incidence at conception much greater, about 97% result in spontaneous loss</p>
<p>Females of short stature and infertile Neck webbing and widely spaced nipples
Intelligence and lifespan is normal
Female because there is no Y chromosome</p>
<p>What is 47,XXY mutation known as?</p>
<p>(Klinefelter syndrome)Incidence: 1 in 1000
Tall stature, long limbs
Male but infertile, small testes, about 50% gynaecomastia
Mild learning difficulties</p>
<p>What are the terms used to describe complete or incomplete retention of DNA during a mutation?</p>
<p>Balanced or unbalanced</p>
<p>What is the definition of a balanced translocation?</p>
<p>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</p>
<p>What is meant by reciprocal translocation?</p>
<p>Involving breaks in two chromosomes with formation of two new derivative chromosomes</p>
<p>What are the different types of Structural abnormalities?</p>
<p>Deletions
Insertions
Inversions
Translocations</p>
<p>What is the effect of unbalanced translocation on the gametes produced?</p>
<p>Production of gametes with, partial trisomy and partial monosomy, this will result in offspring with abnormal phenotypes</p>
<p>What are accrocentric chromosomes?</p>
<p>One of the arms of the chromosome is very short</p>
<p>What is robertsonian translocation?</p>
<p>When the two longer arms of accrocentric chromosomes combine, the short arms are lost and also fuse together</p>
<p>What does Robertsonian translocation result in</p>
<p>Balanced - normal gametes</p>
<p>Unbalanced - Trisomy and Monosomy</p>
<p>What is pericentric inversion?</p>
<p>When the inversion takes place over the centromere</p>
<p>What is polymorphism?</p>
<p>The natural genetic variation within a populaiton</p>
<p>What are the different types of genetic mutations?</p>
<p>Germline or somatic</p>
<p>Gene disruption /disease-associated</p>
<p>Polymorphism</p>
<p>What are the types of non-coding mutations?</p>
<p>Coding mutations -</p>
<p>Silent – synonymous e.g. CGA (Arg) to CGC (Arg) (GIVES THE SAME AMINO ACID)</p>
<p>Missense (A MISSENCE MUTATION IS A POINT MUTATION WHICH A SINGLE NUCLEOTIDE CHANGE RESULTS IN A CODON THAT CODES FOR A DIFFERENT AMINO ACID)</p>
<p>Nonsense (CODON FOR AMINO ACID IS CHANGED TO A CODON THAT CODES FOR A CHAIN TERMINATING CODON)</p>
<p>Frameshift – deletion / insertion</p>
<p>What are transitions - point mutations?</p>
<p>Purine to purine or pyrimidine to pyrimidine</p>
<p>What are transversions?</p>
<p>Purine to pyrimidine or vice versa</p>
Learn Mutation Nomenclature
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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
What do we need for PCR?
Sequence information
Oligonucleotide primers
DNA Nucleotides
DNA polymerase
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
Why is taq polymerase used?
Heat resistant
What is used to separate DNA fragments?
Gel electrophoresis
What is the charge of DNA?
Negatively charged
What does Gel Electrophoresis allow?
Visualisation of DNA fragments
What are the advantages of Gel Electrophoresis
Speed Ease of use Sensitive Robust
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
What are the advantages of Amplification Refractory Mutation System?
Cheap
Labelling not required
Primer design critical
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
What are the disadvantages of Gel electrophoresis?
Need sequence information
Limited amplification size
Limited amounts of product
Infidelity of DNA replication
What is the action of endonuclases?
Recognise specific DNA sequences
Always cut DNA at the same site
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
What are the Advantages / disadvantages of restriction endonucleases?
Simple Cheap
Non-radioactive
Requires gel electrophoresis
Not always feasible
What is used for DNA sequencing?
Chain terminatino method , sanger sequencing, dideoxynucleotides are used
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)
