University of Massachusetts, Lowell
College of Health Sciences
NUTRITION AND GENE EXPRESSION (36.472-572.201)
HSS, Room 120
Thu: 6:30 PM-9:30 PM
Spring, 2014
Professor Garry Handelman
Office: 308 Weed Hall
Garry_Handelman@uml.edu
978-934-4503
Office hours:
Mon, 1:00-2:30, Thu, 2:00-3:30
or by appointment.
INTRODUCTION
The goal of this course is to understand the genome, and how changes in diet affect
expression of different genes. The genome carries the complete hereditary information for
the organism, but DNA is more than a collection of molecular sequences of bases. The DNA
molecule must physically function in the creation of the specific proteins of which the
organism is made. DNA is dynamic, and functions through the production of RNA, which is
then used to make proteins. Some forms of RNA also perform other functions. The controlled
production of RNA, typically followed by synthesis of protein, is termed GENE EXPRESSION.
You have two copies for most of your genes: one copy inherited from each parent. If
one copy of a gene is active in a cell, the other copy is active in most cases. If you inherit a
good copy from one parent, and a defective copy from the other parent, you are OK most of
the time; if both copies have a defect, that can be a serious problem. We will talk about
inheritance of genes, how genes work, and what can happen if the sequence of a gene is
altered. Your DNA is duplicated when body cells divide (mitosis), or when reproductive cells
divide to produce ova and sperm (meiosis). Mutations occur when the child receives DNA
with a different sequence than the genes from the parents; it’s important to know that most
mutations are harmless and seem to have very little effect on the offspring.
Most cells of the body contain the complete genome, but any cell usually only
produces proteins from a fraction (about 40%) of its genes. We will discuss the selective
mechanisms (called transcriptional control) used by the cell to only activate certain genes.
We will review the entire process: the DNA sequence is read into RNA, the RNA is
processed to mRNA, and the mRNA is read into protein. Some genes produce RNA that
functions for gene regulation (such as RNAi), but is not read into protein.
We will examine how deficiencies or excesses of key nutrients (for example,
carbohydrates, fatty acids, iodine, folate, calcium, vitamin D, iron) affect gene
expression. You should develop a sense of how your own gene expression can change
as you change your diet. There are dietary changes that may lead to long-lasting
changes in the activity of different genes.
Some people show important genetic variations that affect their responses to
dietary components. This new area of nutrigenomics will be critically examined, with a
discussion of new methods that will expand our understanding of diet and the genome.
COURSE OBJECTIVES
To achieve these objectives, you will need to make a series of sketches of
the genome and how it functions, and build a portfolio of these diagrams.
For example, regarding gene expression, you can begin with a very simple sketch:
DNA→RNA→protein. This sketch will be modified with additional information,
as you make further sketches that add more complexity and detail.
This series of illustrations, that you make yourself, will lead to a comprehensive
overview of the genome, its functions, and interaction with changes in diet.
TOPICS FOR STUDY OF THE GENOME

Overview of the human genome: Most cells contain the entire genome, but
each tissue only uses a portion of the genes that are present.

DNA duplication and mechanisms of inheritance: how copies of the parental
genes are provided for offspring. Most genes are present in two copies, and
this is fundamental to understanding mechanisms of inheritance.

Principles of gene regulation: the mechanisms that allow genes to
be in the active state, or be dormant (not expressed).

How does gene expression change in response to changes in diet? The changes
that occur in the activity of these genes, in our daily lives.
ASSIGNED MATERIALS
The reading assignments will come from the scientific literature in nutrition. Course
readings will be distributed in advance for each section of the course. There may be 1-2 papers
assigned for each lecture. We will examine several papers in considerable detail, to arrive at an
overview of the methods appropriate to the study of nutrition and gene expression. Lecture notes
and supplemental material will be provided. You will need to utilize the broad range of materials
available to support the content of each lecture, including textbooks, PubMed and google
searches. I will also make available some useful online texts on nutrition and gene expression.
All class materials will be posted at my website:
http://health.uml.edu/HandelmanNutrition/Handelman%20lab%20teaching.html.
Homework assignments will include extensive drawings of molecules and biochemical
pathways, and critical summaries of assigned papers for class discussion. Homework
assignments will not be collected; you may be asked to discuss the assignments using the
blackboard, and to lead class discussion of the readings.
At the start of the lecture, I may distribute a set of questions for you to consider as the
class progresses, and that you should attempt to answer during class. At the end of the lecture,
we will discuss the questions that were handed out.
CLASS PRESENTATIONS
The class will be organized into 6 groups, and each group will have a project that
will lead to a class presentation. The dates are shown on the class schedule. The topics
will be assigned to develop the concepts given in the previous week’s lectures, leading up
to the exam or quiz on those topics.
Your group will have 45 minutes for its presentation, and should prepare a brief
(1-page summary) to distribute to the class at the start of the presentation. There will be
no presentations scheduled at the end of the semester, to allow you focus on preparations
for the final exam.
OFFICE HOURS
I will be available to meet with students in 308 Weed Hall on Monday, 1:00-2:30, and
Thursday, 2:00-3:30. If you want to schedule an appointment, please Email me at
Garry_Handelman@uml.edu, or leave a message at 978-934-4503.
GRADING
The graded assignments are indicated on the class schedule, and the table below. There
are 140 points possible in this course. The exams and quizzes will be based substantially on
material covered in the lectures, and will require use of illustrations, provided by the instructor or
drawn yourself during the exam. The Final will cover all course material, and will require you to
integrate information you have gained throughout the semester. Material for each exam and quiz
will be reviewed at the previous lecture.
Students enrolled at the 500 level will be responsible for a research paper. The
requirements for this paper will be discussed.
The points for the course shown below. There are 140 points for the whole course.
ASSIGNMENT
QUIZ
EXAM #1
QUIZ
LAST EXAM
DATE
Feb 13
Mar 13
April 10
Exam
Week
POINTS
20
50
20
50
Grades are assigned on the following scale: A+ =95-100; A =90-94; A- =87-89;
B+ =84-86; B =80-83; B- =77-79; C+ =74-76; C =70-73; C- =67-69, D+ =64-66;
D =60-63; F = anything less than 60.
Academic Honesty: All students are advised that there is a University policy regarding
dishonesty and cheating. It is the student’s responsibility to familiarize themselves with these
policies. If necessary, contact your advisor or instructors for clarification of these policies.
LECTURE OUTLINE: NUTRITION AND GENE EXPRESSION
Date
Topics
Jan 23
Course overview: Structure of the human genome
Location of genes for defined functions on specific chromosomes.
The basic mechanisms of gene expression: the genetic code.
The molecular basis of inheritance.
Transfer of hereditary information to tissue cells (mitosis) and
to germ–line cells (meiosis).
Dominant and recessive mutations.
Jan 30
Further discussion. dominant and recessive mutations.
Genetic recombination and effects of crossing-over during meiosis.
X-linked inheritance and gender-specific effects.
The Barr body (inactivation of one X-chromosome) in cells of the female.
Mutations: how they occur, and when they have effects on gene function.
Effects of mutations in protein-coding domains, and other parts of the gene.
Feb 6
Important genetic disorders with a nutritional component: special diets
that are required for management of these disorders.
Population biology and potential effects of shared recessive genes on
the offspring.
Genetic screening: current and future applications.
Review for Quiz #1.
Feb 13
QUIZ (20 points). Lectures: Jan 24-Feb 6.
Overview of gene regulation: promoters, transcription factors, synthesis of
primary transcripts, production of mRNA, translation to make protein.
Key question in gene regulation: how does the switch turn genes on and off?
What are the mechanisms that regulate transcription factors?
Transcription factors specific for DNA regulatory domains.
Feb 20
CLASS PRESENTATIONS: mutations that affect nutrient requirements.
Transcriptional regulation (continued):
The formation of the transcription complex, and termination of transcription.
Blackboard exercise: the complete structure of a gene, and mechanisms
for synthesis and expression of an RNA transcript...
Editing of the primary RNA transcript to produce mRNA.
Feb 27
Example of diet effects on gene expression: Dietary effects on
genes involves in cholesterol metabolism, and genes that regulate zinc.
The problem of animal models, and use of these models
for much of our current data..
The specificity of transcription factor binding sites in the promoter:
effects of mutations in promoter DNA sequence.
Research methods used to study how transcription is regulated.
Mar 6
Introduction to effects of dietary patterns of daily life on gene expression:
Fasting state, low-carb diets, high-carb diets.
Review for midterm exam.
Mar 13
MIDTERM EXAM (50 points): All topics through March 6.
Mar 20
No class: Vacation break
Mar 27
CLASS PRESENTATIONS: Effects of extreme changes in diet
on gene expression.
Further discussion: high-carbohydrate diet effects on gene expression,
and comparison to the biology of the fasting state.
Apr 3
Gene arrays: the science of evaluating the regulation of thousands of
genes in single experiment..
Further discussion of micronutrients that effect gene expression: vitamin A, iodine,
vitamin D, iron.
Review for quiz on April 10.
Apr 10
Effects of different kinds of dietary fat (polyunsaturated and saturated
on gene expression.
Gene regulation by dietary iron: control of mRNA translation.
Analysis of mechanisms for transcription factor activation and
inactivation.
Apr 17
QUIZ (20 points): Effects of fasting and high-carb intake on gene expression.
Epigenetics: DNA methylation and others that control gene activity,
dietary influence, and effects on subsequent generations
April 24
CLASS PRESENTATIONS: Gene expression, dietary profiles,
weight gain and weight loss.
Small inhibitory RNA molecules that control gene expression.
RNAi: a technique for suppressing individual genes, and potential
clinical applications.
Further discussion: mutations that require special diets for health.
Importance of single-nucleotide polymorphisms for determining response to diet,
and application to genome-wide association studies (GWAS).
May 1
Review for Last Exam
May 5-12
EXAM WEEK: FINAL EXAM (50 points), Cumulative.