Question

Part 2: Introduction to a GWAS

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 CC ATCC GG AATCTT CC GG | AA TTGT AG AACC GG AT GGI GAGI AGAG G АТ АА ТАС GGITTITT TIGG GT TAG AG TAT C AAAC AGTTTT TGG GGTT GG AG AG * CC AT AC GG GG TT TT CC GG AG TT GG AG AG CC GG AT * CC AA AC CG GG TT TT CT GG AA TT QT AG AG CC TT AT CC AA AC GG AG TT TT CT GG GGTT GG AG AG CC GT AT сс AT cc ca AA тт AA ст ва АА тт ат АА АА ссат AT CC AT CC GG AA TI AA TC GG AA TI GG AG AA CC GG IT CC AT CC GG AA TT AA CC GG AA TT GG AA AA CC GT AT CC AA CC GG AGTTAA TC GG GG GG AA AA CC TT AT C G AATTAA TIGGAAT GT AA AA ΤΑΙ M TO GG AATTAATC GG AATTI GG AG AA AT G AATTAA G AATT GGI ΑΑΙ ΑΑΙ GT AT TAA G AG AA G C G G | AAIAAI Table 1. Nucleotides at 17 Different Loci in Two Groups of Dogs.

Now, let’s explore how a GWAS works using a simple example with just a small number of loci to examine (when this is done for real, computers are needed and thousands of loci can be tested for these associations). Scientists compare the SNPs in two groups of dogs: dogs with white fur and dogs with black fur. If one type of SNP is found much more frequently in dogs with white fur than in dogs with black fur, the SNP is said to be “associated,” to the white color. The associated SNPs mark a region of the genome that could contain a gene involved in determining the white coat color. Table 1 shows alleles at 17 loci in the genome sequences of eight different dogs, four with black fur and four with white fur. Each SNP locus is represented by two nucleotides, one from each parental chromosome. To determine whether any of these loci have SNPs associated with white coat color, you will compare the SNPs of the dogs with black fur and the dogs with white fur displayed in Table 1. (next page)

Look at the data and try to see the patterns. For some loci there are no variants for the dogs that were tested. These data are not useful to us so you can ignore those. Among the rest, look for situations where there is no clear association between one SNP variant and a trait. There are several of these in the data – you should see no preferential association of one of the variants with a particular trait. Then look for situations where a SNP is 100% associated with the trait – there is one variant associated with dark fur and the other is associated with the light fur. These are the easiest ones to see. Then look for a case which mimics what we were (going to be  ) working with in our dog project: a strong association between a particular variant and one trait (like dark fur) and no association for the other. We will talk about variants that are “somewhat” associated in the next exercise and how they can be assessed. After you’ve looked at Table 1 on the next page, please answer these questions:

1.Identify the loci that clearly have no association with the trait of fur colour. Explain.

2.Identify a locus or loci that show(s) a 100% association with fur colour.

3.Identify a locus or loci that show(s) the situation described above regarding our dog project – a positive association with one trait but no association with the other.

4.Give two reasons why a SNP might show a positive association with a particular trait, such as coat colour.

Answer 1

1. The loci that clearly have no association with the trait for fur color are locus 1, locus 9, locus 11 and locus 15. Here in these loci, only one type of SNPs, ie. the same nucleotide from both parent can be observed for both these traits in all the cases.

2.The locus 7 shows a 100% association with fur color. A loci is 100% associated with fur color when all the dogs with white fur have the same nucleotide pair at a particular loci, while all the dog with black fur have another pair of nucleotide at another loci.

3. Locus 3, 5, 13 and 14 shows a strong positive association with one trait and no association with other. Locus 2, 6, 10 and 12 shows a weak positive association with one trait and no association with other.

4. An SNP shows a positive correlation with a particular trait because the cause for that particular trait can be the SNP. Another reason may be because the SNP is linked to the allele that causes that particular trait.