Genetics 282 Problem Set 3 Your Name: Manuel Briceno Group Name: CRISPR Crew I will be grading the entire problem set for completion, but only the first page for accuracy. You can also post your answers to these questions on Sakai to get participation points! Problem Set 3.0: Annotated Bibliography 1. What still confuses you about the information we have covered so far? - Nothing confuses me about the information covered so far. 2. If nothing confuses you, what do you think is the most interesting and why? - Inheritance of link genes is the most interesting because it is nice to see more complicated methods of inheritance that build on the foundational concepts that I have learned so far up to taking this class. This was my first time trying out peer review with an annotated bibliography. 3. What did you like about it? - I thought that it was a good way of getting feedback . 4. What did you dislike about it? - The grading criteria was a little vague, making it difficult to judge what was worth removing points for and what was fine. 5. What suggestions do you have for the future? - Some more specific grading criteria in the grading rubric. Problem Set 3.1: Genome sequencing and SNPs 3a. A child has a rare recessive disease due to a mutation in Gene X; both his parents are healthy. What would you expect to see at Gene X if you sequenced everyone in the family? - You would expect to see each parent with one Dominant allele ad one recessive allele, while the child would have both recessive alleles 3b. If a child had a rare dominant disease due to a mutation in Gene Y; both his parents are healthy. What would you expect to see at Gene Y if you sequenced everyone in the family? - You would expect to see both parents to be homozygous recessive and the child would be heterozygous with on dominant and one recessive allele 3c. In both cases, how many differences in DNA sequence would you expect to see if you compare the kid’s genome sequence to their parents genome sequence? - There would be just one difference in each of the above cases. Problem Set 3.2: Quantitative Genetics – GWAS 4. One trait that scientists have done GWAS for is ‘body mass index’ in humans. Body mass index (BMI) has a high heritability of about 50%. This was done in a population of 20,000 people of European descent. The results are below. All the SNPs that are colored are significantly associated with body mass. 4a. What do the dots represent? - SNPs that were genotyped 4b. What does the Y axis label represent? - Significance 4c. Sometimes there is no significance line, and the significant SNPs are represented by color. About how many novel significant SNPs were found? - 18 4d. Which SNP do you think has the biggest effect size? - FTO 4e. Is this SNP the causal mutation affecting BMI? - No 4f. This GWAS for BMI only explains 1.75% of the phenotypic variation. What explains the remaining 48.25% of the variation? - Other genes not yet identified 5. These are GWAS results for a number of human diseases 5a. What do the numbers on the X axis represent? - Chromosomes 5b. Why are some SNPs green? - They significantly predict phenotype 5c. Find an example of two significant SNPs that are linked. For what disease & on what chromosome do you find them? - Type 1 Diabetes has linked SNPs on chromosome 12 5d. For a given disease (say Hypertension), what does it mean that most SNPs aren’t green? - Most aren’t associated with the phenotype 5e. Which disease would you expect to have more variable symptoms: coronary artery disease or Crohns disease? Why? - Crohn’s disease because it is polygenic 6. Most GWAS studies for diseases etc. are done in people of European descent. Why is this a problem for interpreting the genetic basis of disease? - There may be variability or other genetics factors that are being overlooked in these skipped populations. This data is, then, not able to be extrapolated to people not being featured in GWAS studies. Bonus GWAS Questions How is heritability different from heredity? - Heritability tells how much variation in phenotype is due to variation in genotype, whereas heredity relates to the passing of traits from parents to offspring. Would you do a GWAS on a trait with heritability of 0? Why or why not? - You would not because all variability is attributable to environmental factors. Doing a GWAS would not tell us anything. The effect sizes for the SNPs linked to performance on IQ tests are very very small. Why does that make it unlikely that we can genetically engineer humans with super high IQ? - A small effect size means that phenotypic variation of IQ cannot be explained by the given SNPs. This means most of IQ is not determined very much by your genetics True or False: SNPs that are associated to disease using GWAS design should be immediately considered for further molecular functional studies. Explain your answer. - False, SNPs are correlative. The given SNP is not the spot that causes the phenotypic mutation but rather tells you its possible location Problem Set 3:3: Personal Genomics 7. One of the interesting applications of GWAS studies is to generate polygenic risk scores. This approach takes a person’s genotypes, and based on the results of a GWAS, predicts their traits. Most commonly, this is used to predict disease risk. Some of the online genome companies (like 23andMe) will calculate these for you based on your genotypes. Would you want to have this done? Why or why not? You should be able to make arguments both based on personal preference and science. - I would not because the science seems very faulty. The fact it is simply a probability based on similarity between SNPs of sampled populations means that it is not actually very worthwhile. 8. Pathway Genomics is a company based out of San Diego that offers a number of DNA testing kits. Below is one that will use your genotype data to determine the best skin care plan for you. What do you think about the validity of this product? Why? - I see no problem if people want to buy it if it is made clear just how accurate the process is. If people understand that it has little validity but want to get it anyway, then I see no reason they shouldn’t. 9. Do you think law enforcement should be able to use genetic databases to confirm suspects? Why or why not? - I think that it should be allowed but with safeguards. Ultimately, I think the benefit of solving more crimes outweighs the privacy risk. I do believe that there should be checks to make sure it is only used for this purpose and not expanded without widespread democratic support. 10. Do you think people should be able to analyze DNA from envelopes (see below)? Why or why not? - I think the justification is the same as above. I see no issue if consent is given and there is utility to it, then I think it can be justified. 11. At this point, if money were not an issue, would you want to sequence your own genome? Why or why not? - No, simply because I don’t want to know any genetic risks I have nor do I think there would be much value to it outside of knowing these risks.
