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