CB 399: From Genotype to Phenotype: Elucidating the mechanisms of human disease through Genome-Wide Association Studies Fall 2011

Intellectual Unit:

From Genotype to Phenotype: Elucidating the mechanisms of human disease through          Genome-Wide Association Studies
Course Director: Fred Winston
Curriculum Fellow: Leah Brault
Lecturers: Dan Chasman, Mark Daly, Barbara Stranger

Since its development, whole-genome genotyping has become an invaluable tool for identifying genetic variants that play a role in many human diseases.  One application of this technology, genome-wide association studies (GWAS), has been crucial in unraveling the complex genetic nature of diseases such as Crohn’s disease, Alzheimer’s disease, and diabetes.  GWAS has been very successful as a method for identification of regions of the genome associated with specific disease, pinpointing thousands of disease-contributing variants in a short time.  As this field of research moves forward into the next decade, the importance of detectingmany more and rarer variants is growing as the numbers of diseases currently studied expands.  This nanocourse will explore the current methods and technologies used in GWAS, as well as theirapplication in the identification of variants that both directly contribute to human diseases and phenotypes, as well as those that influence the regulation of genes involved in these traits.



First Session: Tuesday, November 8, 2011 9:30 am – 1 pm
Location: New Research Building, room 350

Second Session: Tuesday, November 15, 2011 10 am – 12:30 pm
Location: TMEC building, room 447


Registered students for this nanocourse will be split into two groups.  Your group will be assigned to you after the enrollment deadline has passed.  Each group will be given a different scientific paper following up on the results of a GWAS, which attempted to identify the genetic contribution to a particular disease.  (One group will read Harismendy et al., and the other will read Musunuru et al.)  Each student must read the paper, and then write one page addressing the following questions:

  1. What were the results of the original GWAS?  Were the data generated by the GWAS clear-cut, or more difficult to interpret?  How well did they establish potential causality of the disease?
  2.  How did the authors of the paper you read follow up on these results?  What bioinformatics or biochemical methods did they use to more definitively identify or prove a genetic association?
  3. How might the effects of environmental interactions influence the disease trait?  How might these effects have influenced the results of the original GWAS?
  4.  Given these results, what do you feel is the value of a GWAS is determining genetic mechanisms of disease?

      This assignment must be completed and e-mailed to the Curriculum Fellow, Leah Brault (lbrault@genetics.med.harvard.edu), by 9:00 a.m. on Monday, November 14th.  Please also bring a hard copy to the discussion session on Tuesday, November 15th.  Your answers will be used as the jumping-off point for the discussion, so be prepared to talk about what you have written!



DROP DEADLINE: Tuesday, November 1, 2011