Genome variation

Question 1

What are the different types of genome variation?

Answer 1

• Macro = numeric (trisomies), structural (translocations)
• Micro = microdeletions/ duplications, CNVs, microsatellites
• Molecular = small indels, substitutions

Question 2

What is CNV?

Answer 2

• Should have 2 copies of each gene
• Sometimes have a deletion - Copy number will be 1 instead of 2
• Sometimes have a duplication - copy number will be 3 not 2
• CNVs are smaller than microdeletions/ insertions - less likely to be pathological
• May be inter- or intragenic

Question 3

What is non-allelic homologous recombiantion?

Answer 3

• Misalignment between chromsomes - get crossing over causing deletion in one and duplication in another

Question 4

What are microsatellites?

Answer 4

• Repetitive units - number of repeats and total length of microsatellite varies between individuals
• The number of repeats in a particular allele will be passed on - multiallelic inheritence
• Named after the number of nucleotides that is repeated (eg dinucleotide = (CA)(CA)(CA)(CA))

Question 5

What is the polymerase slippage model?

Answer 5

• During replication, polymerase and subsequent reattachment may cause a bubble to form in the new strand
• Slippage is thought to occur in sections of DNA with repeated patterns of bases
• Then DNA repair mechanisms realign the template strand with the new strand and the bubble is straightened out
• The double helix created is therefore expanded
• Cannot occur in DNA without repeated base patterns
• may be intronic or UTR (affect gene expression), or exonic

Question 6

What are indels?

Answer 6

• Insertions and deletions
• Caused by misalignment and replication slippage
• Can occur anywhere in the genome

Question 7

When are indels most likely to be pathogenic?

Answer 7

• An indel that isnt divisible by 3 -> frameshift mutation

Question 8

What is an SNP?

Answer 8

• Change in a single nucleotide
• Not always pathogenic
• Generated by mismatch repair during mitosis
• May be in a gene, promoter, non-coding region
• Without a deleterious effect or population annihilation, SNPs dont disappear
• Can only be two different combinations in reproduction - biallelic

Question 9

What are the different outcomes of SNPs in a gene?

Answer 9

• No AA change - synonymous
• AA change - non-synonymous/ missense
• Introduce stop codon (nonsense)

Question 10

What is the main difference between SNPs and point mutations?

Answer 10

• SNP will not usually cause mendelian disorder
• Minor allele frequency is high
• Therefore SNPs are considered to be a form of common variation in the general population

Question 11

What is ‘common’ variation?

Answer 11

• Rare polymorphism - minor allele frequency 1-5%
• Common - MAF >5%
• All variants start off rare, but evolutionary forces affect whether or not it remains rare

Question 12

Give 4 types of common genetic variation

Answer 12

• SNP (biallelic)
• Indels
• Microsatellite (STRs) (multiallelic)
• CNV (multiallelic)

Question 13

Why is gene mapping useful?

Answer 13

• Neighbouring loci on a chromosome have a tendency to stick together when passed on to offspring
• Therefore a disease is often passed on with a specific marker allele - can conclude that the gene responsible for the disease is located close to these markers on the chr

Question 14

Give an example of a disease caused by a variation

Answer 14

• Cystic fibrosis

- CFTR - deltaF508

Question 15

Give an example of a SNP causally associated with a trait

Answer 15

• Melanocortin 1 receptor
• Binds aMSH -> eumelanin
• aMSH doesnt bind -> phaeomelanin
• Some SNPs tend towards lack of binding and therefore red hair, freckling, pale skin