Course Meeting Times

Lectures: 1 session / week, 2 hours / session


Recommended prerequisites are:

7.03 Genetics

7.05 General Biochemistry

7.06 Cell Biology

7.28 Molecular Biology

Course Description

Human genome sequencing has revolutionized our understanding of disease susceptibility, drug metabolism and human ancestry. This course will explore how these advances have been made possible by revolutionary new sequencing methodologies that have decreased costs and increased throughput of genome analysis, making it possible to examine genetic correlates for a variety of biological processes and disorders. Each student will have the opportunity either to have the sequence of his / her own DNA determined or to explore publically available genome reference samples to understand what can be learned from examining genetic markers that can correlate with disease risk, carrier status and medication response.

We will discuss how an individual's risk of developing a disease can be assessed based on small genetic changes in nucleotide sequence as well as on larger structural variations that affect entire regions of a chromosome. We will also discuss how maternal ancestry, paternal lineage, and human populations can be analyzed by examining chromosomal or mitochondrial DNA. We will read papers from the scientific literature to understand how genetic analysis is influencing treatment for patients who have cancers with specific mutations that can be targeted with tyrosine kinase inhibitors, such as individuals with chronic myelogenous leukemia who have the BCR-ABL gene fusion.

Genomic analysis has also spurred the development of new drugs that might be helpful for patients in the general population, such as PCSK9 inhibitors for patients with hypercholesterolemia, an approach that was driven by the observation that people with a mutation in this gene have abnormally low LDL cholesterol. We will also debate social, legal and ethical aspects of genetic testing. The course will combine discussions of primary scientific research papers with hands-on data analysis and small group presentations. We will take a field trip to the Harvard Medical School Center for Personalized Genetic Medicine to learn how genomic sequencing informs clinical decision making.


This seminar will meet weekly for 2 hours. Students are expected to read and evaluate two research papers prior to each session and should email the instructor with one question or concern regarding the methods or conclusions of each assigned paper the evening before each class. On the day of the class, a different student will be randomly selected to lead the discussion for each figure in the assigned paper. All members of the class will need to be prepared to discuss all of the figures and are expected to participate in the discussion of both articles.

Course Objectives

During this course, students will develop skills in the following areas:

  1. Understand and evaluate the primary scientific literature.
  2. Become familiar with sequencing and analysis methods that are commonly used to perform genetic studies.
  3. Gain experience with oral presentations of scientific research in a seminar format.


The class is graded on a pass / fail basis. Evaluation will be based on participation in discussion, completion of the written and oral assignments, and class attendance.

Optional Exercise

This course has an optional genotyping exercise. This genetic analysis will be done after we cover the first several topics of background material, so that students are better informed about genetic testing before deciding whether to participate. The purpose of this exercise is to enhance the learning experience of students and teach important concepts of clinical genomic testing, such as the validity and utility of single nucleotide polymorphism testing. Students can select a gene identified from this exercise as the basis of a topic for their presentations, or they can select any other gene of interest, e.g., identified from one of the reference genomes or from papers in the literature.

This optional genetic testing will be provided by an outside company, 23andMe, and we are not endorsing their methodology or services. The anticipated cost will be $99 and it may be possible to negotiate a further discount depending on the number of students who enroll. This exercise is completely optional, and students who do not want to have their genome sequencing performed can use publically available data for all of the assignments. All genetic information is private, and students will not be asked to share this information with other members of the class. Other individuals in the class will not know whether you are participating in the genotyping exercise or what the results are unless you choose to tell them. Students are encouraged to contact genetic counselors if additional support and advice regarding testing results is needed. This exercise is completely optional and confidential.


1 Introduction  
2 Classical approaches to sequencing  
3 Contemporary sequencing methods  
4 Single nucleotide polymorphisms  
5 Copy number variation  
6 Tracing human populations  
7 Genome wide association studies  
8 Field trip to the Harvard Medical School Center for Personalized Genetic Medicine  
9 Genomic analysis and targeted therapies Written Assignment Due
10 From rare mutation to mainstream drug target  
11 Mosaics and chimeras: When genetic analysis goes astray  
12 Crowdsourcing genetic studies  
13 Understanding the causes of rare diseases  
14 Final presentations Oral Presentation Due