Question

We are studying a hypothetical population that represents the result of recent admixture (within the past three generations) between a high altitude adapted Nepalese population and a population from lowland India. Using GWAS, a SNP significantly associated with respiration rate is identified on the long arm of chromosome 17. With reference to this SNP, write an accurate single sentence statement indicating what we now know about the causal genetic basis for variation in respiration rate. In other words, what do we now know about the specific genetic variant that is responsible for this variation in respiration rate?

Answer 1

This SNP is the result of a single point mutation that was advantageous for surviving in the high altitudes of Nepal and hence got positively selected for in Nepalese people over many generations becoming fixed or almost fixed.

(You may choose to not mention 'becoming fixed or almost fixed' if it's too long)

GWAS (genome wide association study) is a study that tries to find any strong associations between a certain phenotype and an SNP or few SNPs. For this they have to take a large sample consisting of both people that have a trait and those that don't. The larger rhe sample the better. They then try to find if any SNP appears way too often in people that have the trait. If they do then it is very likely that that SNP contributes to the person developing that trait. In this population, we have both Nepalese people and lowland Indians. The SNP was found way too often in Nepalese and very less often in lowland Indians. This means there is a very good chance that this SNP is a result of a single nucleotide mutation that happened to give Nepalese better respiration rate to cope with the high altitude. This resulted in people with the mutations being selected for which increased the frequency of the mutation in their population. The stronger the association, the more likely it is that the SNP got fixed in the population, (meaning it's frequency became 1). Since the new population is ony 3 generations old, the SNP is still in a high enough frequency for enough people to have the mutation to be able to find a strong association. A new population also means there are more people homozygous for the mutations which means s stronger phenotype (excellent respiration rate) which helps form even stronger associations. It could also get lost over generations if the lowland Indians outnumber the Nepalese people by many fold.