sample questions

1. A baby presents at a clinic with a severe neurodevelopmental disorder that you suspect may

be caused by a de novo (sporadic) genetic mutation. Describe how you could identify

candidate Single Nucleotide Polymorphisms (SNP) that may cause the disease, without

having access to samples from the child’s parents or from any other family member. Briefly

describe a different approach that you could use to identify Copy Number Variants (CNV)

Lecture 5: Complex Traits
– Includes methods for identifying SNPs using GWAS, and understanding the use of SNP arrays.

2. Define linkage disequilibrium, haplotype, and Tag-SNP.

The table below shows the frequency of alleles (called A and B) at four different loci

numbered (1-4) measured in a human population. The frequency of the haplotype ABBA was

observed in 3% of the population (where the alleles at each locus are shown in order,

starting with Locus 1). Do you think these alleles show evidence of LD, and why

Lecture 5: Complex Traits
– Explains Tag-SNPs and includes examples of LD blocks and haplotypes in GWAS.

3. For Genome Wide Association Studies (GWAS), variants present in the tested groups

(patients and controls) can be identified using SNP arrays (often called bead arrays, high

density arrays, microarrays or similar). Describe how these arrays can be used to

characterise up to 1 million SNPs (Single Nucleotide Polymorphisms) in a single individual in

a single experiment. Describe how the method works – that is, how the base present at each

potential polymorphic site can be identified.

Lecture 5 and 6:
– Cover Illumina Bead Arrays, SNP identification using high-density arrays, and how fluorescent signals identify base changes.