An Innovative Project

Conceived As Part Of A Natural

Sciences Course
Boston University
2011 Instructional Innovation Conference
Andy Andres & Peter Busher
Division of Natural Sciences and Mathematics
College of General Studies
Boston University

Innovation OUTLine
About the Natural Sciences Division at the College
of General Studies
The Purpose of Natural Sciences 201, an
interdisciplinary course designed for non-majors
Part of a Core Program at CGS
Help create better citizen scientists
Major paradigm: Human Genetics and the Human
Genome Project

Project Description
Outcomes

About the Natural Sciences Division at

the College of General Studies: Purposes
of NS 201
Exciting pedagogical opportunity because
our students are non-majors and this is a
required course
Further understanding of nature and the
role humans play in the world
Learn the process of science through
active participation
Develop critical thinking skills
Develop the students sense of becoming
active citizen scientists
Encourage participation in scientific
problems they will encounter in the
lifetimes

Major Paradigm of NS
201: Human Genetics
Historical Paradigms in our Courses:

Copernican Revolution in Cosmology

Newtonian Revolution in Physics
Darwinian Revolution in Biology
Included other major paradigms in: Physics,
Chemistry, Astronomy, Developmental Biology,
Cell Biology, Ecology

A new course was designed to help meet goal

of creating more informed citizen scientists
Human Genetics and The Human Genome
Project

NS 201 Topics
What do we know in Human
Genetics

Cells
Mitosis, meiosis
Proteins
Chromosomes
DNA structure, function and
replication

How do we know this, an

historical perspective

Mendelian classical genetics

Morgan and modern genetics
Franklin, Crick and Watson
Human Genome Project

NS 201 project: Human

Genome Project
Apply course knowledge
in Human Genetics
Understand importance
of Human Genome
Project
Understand personal
genomics and its future
Communicate scientific
knowledge to student
peers and faculty

Outline of the
NS 201 project
Students learned about
human traits and genetic
polymorphisms
In laboratory, students
isolated Wheat Germ DNA
We guided then to
professional genetics
databases (GWAS Catalog,
OMIM, etc.) to research
favorite human traits
Students wrote up summary
of what is known about the
genetics of their human trait

NS 201 project: Human

Genome Project
Research
Your gene and SNP of interest
Data bases: GWAS, BLAST,
NCBI, WikiGenes, SNPedia
Research papers

Wet Lab
DNA extraction, amplification
(PCR)
Sequencing

Scientific Poster Session

Visualization of knowledge
Communication of knowledge

Researching the Project

Step 1: Finding Genes
of Interest
Limited to benign
traits (some
examples):

Hair color
Eye color
Taste
Freckles
Resting heart rate
Smoking cessation

Know what gene, what

phenotypes, what SNPs

Sequencing their own

genome: The Wet Lab
Each Group chose a
trait/SNP to sequence

Resting heart rate

Bitter taste
Hair morphology
Skin and eye
pigmentation

Isolate their own DNA

Amplify DNA (PCR)
Clean up sample
Sequence DNA

Sequencing Results

Sequencing Results

Sequencing Results

Sequencing Results

Communicating
SCIENTIFIC
KNOWLEDGE
Scientific Poster
Session
Visualization of
knowledge
Communication of
knowledge

Communicating
SCIENTIFIC
KNOWLEDGE
OCA2 GENE

Researching the HERC2 Gene and the Eye Color Trait

Jason Kann, Tom Levitsky, John Martin & Matthew Serrano

By: Molli M., Alexis M., Mike N., Vickiana R.

Introduction

Eye color is one of the most dening and noticeable

traits in humans. Geneticists have long postulated
that the appearance of eye color is determined by
the OCA2, which regulates the amount of Melanin
produced in the iris. However, recent ndings show
that the HERC2 gene (SNP: rs916977) has a high
correlation with people who have blue eyes.

The Big Picture

The HERC2 gene is located on chromosome 15 in

humans. It encodes a protein called E3 ubiquitinprotein ligase, also known as the HECT domain
protein.

Small amounts of Melanin produce blue eyes while

larger amounts produce brown eyes. When we are
born, we all have blue eyes. As we develop in the
womb, our eyes begin to change color, depending
on the genetic information given to us by our
parents.
The HERC2 gene inuences the appearance of eye
color by controlling the OCA2 gene. It effectively
decides whether the OCA2 turns on to produce
Melanin.
Fig. 1 Different eye color
p he no t y pe s. a Blue
(without brown areas). b
Blue with brown spots
(with brown) scored as
unknown in the linkage
and association studies.
c Browngreen/ hazel
(BEY1) with a board
puri- pupillary ring. d
Brown (BEY2), total
brown pigmentation. The
person with blue eye
color (a) represents the
genotype rs12913832 G/
G, while the per- sons
b d r e p r e s e n t t h e
genotype rs12913832 A/
G

Allele Information

The HERC2 gene is considered a haplotype,

which includes 13 SNPs that are present in 97% of
Caucasians with blue eyes.
In the HERC2 gene, the A-allele is associated with a
brown phenotpical expression and the G allele is
associated with a blue phenotypical expression. The
A-allele is dominate, while the G-allele is recessive,
which accounts for brown eyes being the dominant
phenotype in the population.

We conducted our research through a variety of

methods:
SNPedia was used to nd information on the
gene and allele frequency.
PubMedCentral was used to nd journal
articles related to HERC2 and its function.
NCBI was used to nd the DNA Sequence.
The results from our class data were from a
wet lab where we isolated the HERC2 gene.

Conclusion

Fig. 2 The illustration above is a 3D representation of

the HECT domain protein.

Today, there is little known information on the

function of the protein itself. However, with
recently published research, we now know that
the gene is highly associated with the presence of
blue eyes.
Research suggests that the non-coding portion of
HERC2 bind transcription factors to a certain
unknown protein, thereby inhibiting the expression
of OAC2 in humans with the specic haplotype.
HERC2 is located 11.7 kb from the OAC2 gene on
the same chromosome, which encodes the Pprotein responsible for melanin production in the
iris. This likely explains one reasony why the
genes are able to interact.

Allele Frequency
Toscani (Italia)
Maasai (Kinyawa)
Mexican (Los Angeles)
Luhya (Webuye)

While the scientic community still has much to

learn about the impact of HERC2 in our gene pool,
association studies have shed light on one of its
puzzles. It is possible that everyone with the HERC2
gene is related from a common ancestor,
suggesting that the blue eye trait has only surfaced
for a few thousand years.

Hans Eiberg et. al. Blue eye color in humans may

be caused by a perfectly associated founder
mutation in a regulatory element located within
the HERC2 gene inhibiting OCA2 expression.
Human Genetics 123 (2008): 177-187. Print.
Fan Liu, et. al. Digital Quantication of Human Eye
Color Highlights Genetic Association of Three
New Loci. Public Library of Science Genetics
6.5 (2010): 1-15. Print.
Manfred Kayser et. al. Three Genome-wide
Association Studies and a Linkage Analysis
Identify HERC2 as a Human Iris Color Gene.
The American Journal of Human Genetics 82
(2008): 411-423. Print.
M. D. Grant and D. S. Lauderdale. Cohort Effects in
a Genetically Determined Trait: Eye Colour
Among US Whites. Annals of Human Biology
29.6 (2002): 657-666. Print.

Please consult one of the group members to inquire

about further information on this gene of interest.

African (Yoruba)
Japanese (Tokyo)
Han Chinese (Beijing)
European (Utah)
0%

20%

40%

60%

80% 100%

Officially called Oculocutaneous albinism II

Specify human iris colors
Determines eye color; is one of the main eye color genes.
Has blue, green, and brown alleles
Associated with the HERC2 gene
The expression of these alleles in phenotype may be modified
by other genes
Associated with instructing the production of the P protein
Located on the long arm of chromosome 15
Between base pair 28,000,020 to base pair 28,344,457
Mutations in the gene can cause albinism
One mutation in the OCA2 gene is found almost all people
with blue eyes

The OCA2 gene determines eye color: brown, blue, or green

The gene determines how much melanin is produced which codes
for iris color.
The more melanin produced the darker the iris color:
More pigment in the iris=brown eyes or dark eyes (the most
common)
Small amount of pigment in the iris=Green eyes (the least
common)
Little to no pigment in the iris=Blue eyes
Mutations in the OCA2 gene less melanin production less pigment
in iris color blue/light eye color
One mutation almost always leads to blue eye color
Specifically, SNP rs12913832 is associated with blue eye color.

Literature Cited

For Further Information

Chinese (Denver)

Phenotype:

Gene:

Furthermore, because the trait for blue eyes is

recessive, we know that it only effects a small
amount of the population. About one in every six
Americans are born with blue eyes today, compared
to nearly 60% born from 1899 through 1905.

Gujarati Indians (Houston)

African (Southwest USA)

Fig. 1 The illustration above is a visual representation of

the alleles. The information is from our wet lab, conducted
11/19/2010.

Methods

Jason Kann: jekann@bu.edu

Tom Levitsky: vitsky@bu.edu
John Martin: jcmartin@bu.edu
Matthew Serrano: mserrano@bu.edu

Protein:

The OCA2 gene helps make the P protein

Protein is located in melanocytes which are cells producing the
pigment melanin
Melanin determines the coloring and shading of a persons skin, eye,
and hair colors
Melanin is also in the retina, playing a part in determining vision.
Essential for normal pigmentation
The P protein moves molecules in and out of the melanosomes
Melanosomes are structures within the melanocyte cells that produce
melanin
Helps regulate the relative acidity of melanosomes necessary for
most biological processes
A reduced amount of the P protein produces a reduced amount of
melanin creates fair/light hair, eye and skin coloring. It can also
cause oculocutaneous albinism.

SNP:

Haplotype found in 97% of people with blue eyes

Alleles A/G
Sequence: GAGCATTAA [ A | G ] TGTCAAGTTCT
SNP rs12913832 lies in the center of a short, highly conserved
sequence
78% Frequency
Region around rs12913832 controls expression of OCA2
The C allele at rs12913831 leads to the decreased expression of OCA2
thought to be the cause of blue eye color.
The SNP predicts blue eye color. The SNP differentiates people from
one another based on possession of the blue eye phenotype.

A;A (Brown Homozygous)

A;G (Brown Heterozygous)
G;G (Blue Homozygous)
Fig 3. The graph above represents the allele frequency of
the HERC2 gene at SNP rs916977. The information was
taken from a study of 1301 individuals from the locations
listed above.
Fig 4. The illustration below shows the location of the
HERC2 gene on Chromosome 15 in humans.

The Big Picture:

Ancestral backgrounds and populations most associated with the OCA2
gene help to understand the way the P protein has evolved over time.
Information about the SNP rs12913832 gives a deeper and more specific
look into the way the gene is expressed in phenotype. Our SNP causes blue
eyes, showing that its mutation affected P protein production, limiting
pigmentation. By limiting the expression of the OCA2 gene, the SNP
causes blue iris color. It also enabled us to look specifically at the alleles, A
and G, and the sequence making up the SNP. Also allowing us to analyze
data about who has and who doesnt have it. It allowed for us to realize why
different pigmentations occur in individuals and populations, as well as how
the gene is passed on through generations.

Absence of SNP

With SNP

outcomes
Some student reflections on the project
Sequencing and personal genomics has not
been used in a university biology course for
non-majors
Better citizen scientists by exposing students
to the most current genetics research
Acknowledgements: Carol Donovan and
Rayhme Cleary of the College of General
Studies