BurchGene

Biannually Magazine Issued by the Genetics and Bioengineering Department

December 2016 Volume 1 Issue 1 ISSN 2490-3515

DNA DATA
STORAGE
LUIS AND REINHARD REVEAL THEIR
SECRETS: FIRSTHAND ANSWERS
ABOUT DNA STORAGE

Bacterial adhesion and Do you understand You have your chance

biofilms on surfaces DNA structure? in your own blood
A biofilm is a structured consortium of bacteria DNA encodes all of the information for a cell to Stem cells have the remarkable potential to
embedded in a self-produced polymer matrix. reproduce, make proteins, and function properly. develop into many different cell types.

READ ABOUT POPUL AR AND INTERESTING TOPICS IN GENETICS

 2 P o p ular Topics in Genetic s

FROM THE EDITORS

Dear colleagues, students, respected professors, collaborators

and respected readers. The issue you are holding in your hands
is the second edition of the BurchGene magazine. Strong will,
clear goals and love for science drove us to continue helping,
inspiring and bringing simple, accessible and fun scientific
topics to our audience.
As a new science magazine we are always aiming at deliver-
ing fresh, intelligent coverage of hot topics in science and its
comprehension to the scientists as well as to the other readers
interested in genetics and bioengineering.
Since the publication of the very first issue, BurchGene maga-
zine has become very popular among readers. It has been seen
on the streets of New York City and experienced a boom on
Executive editors:
Ahmed Osmanović
the global networks. As a result, we have successfully recruited
Adnan Fojnica
a great number of people to contribute to the current issue. Fatima Mrkulić
We have talked with the associate professor of com-
puter science and engineering at the University of Washington, Editorial board:
Luis Henrique Ceze, who introduced us to the very inter- Prof. Dr. Rifat Hadžiselimović
esting and new topic called “DNA as a memory storage”.
Prof. Dr. Dragan Primorac
Prof. Dr. Damir Marjanović
Also, post-doctoral researcher at the Department of Electrical
Prof. Dr. Mrsada Hukić
Engineering and Computer Sciences at the University of Assoc. Prof. Dr. Amina Kurtović Kozarić
California, Reinhard Heckel, dedicated his time to answering Assoc. Prof. Dr. Enisa Omanović
our questions and brightening our perspectives about capaci- Assist. Prof. Dr. Almir Badnjević
ty of a DNA molecule in storage and its readability. Assist. Prof. Dr. Serkan Dogan
Within these pages you will also discover articles written by
Lectors:
our respected professors and students at the Department of
Monia Avdić Ibrišimović, PhD
Genetics and Bioengineering. Biofilms, stem cell research and Elma Ferić Bojić, MSc
mtDNA diseases are only some of the attractive topics you will Sabina Halilović, BSc
encounter. Last but not least, our students were kind enough
to share with us two research posters. Graphic Design:
The issue is free of charge, and this decision was guided by our
Ahmed Osmanović
belief that knowledge is a right and not a privilege. This would
Publisher:
not have been possible without our sponsors: International International Burch University
Burch University, Nalaz and Somnacare whom we are sincerely
grateful for supporting us every step of the way. Address:
Francuske revolucije bb, Ilidža 71210
Enjoy reading,
Telephone: 033 782-130
The Editors
E-mail: burch.gene.mag@ibu.edu.ba
“Sometimes the smallest step in the right direction ends up
being the biggest step of your life”
-Naeem Callaway

BurchGene Magazine | December 2016

 Popular Topic s in Ge ne t ic s 3

CONTENTS 4 IS DNA THE FUTURE OF DATA STORAGE?

This interesting topic discusses some of the main ideas of bioinformatics as an intersection
between genetics and computer science.

6 INTERVIEW
To better understand work of scientist with DNA as a memory storage, we spoke with Luis
Ceze, an University of Washington professor and Reinhard Heckel, researcher at the Berkeley.

8 BIOFILMS
Many bacteria exist in associations known as biofilms, which are considered as complexes of
microorganisms in which cells stick to each other and often adhere to a surface.
»» p.14
11 STEM CELL RESEARCH
Stem cells are undifferentiated cells in multicellular organisms, capable of reproduction and
giving rise to indefinite number of cells of the same type, as well as other types of cells.

14 RESEARCH OF GBE DEPARTMENT

Our professors and students actively attended many conferences at which they were able to
increase their scientific knowledge, awareness and expertise with which they hope to optimize
the GBE approach.

16 DNA INFO GALLERY

»» p.11 »» p.4 Considering DNA as one of the most important life units, this article provides all basics one
should know about this macromolecule, its basic structural components and function.

18 NUCLEAR GENES ASSOCIATED WITH

MITOCHONDRIAL DISORDERS IN HUMANS
Going deeply into the pores of molecular genetics, this article discovers how correlation between
mitochondrial and nuclear genome affects mitochondrial disorders.

20 mtDNA DISEASES – A STORY OF CRAFTY

TRICKSTERS IN OUR CELLS
Very informative article that represents a continuation of the previous article by sharing some
common ideas while focusing on specific features of mtDNA diseases.

»» p.7
»» p.16 22 POSTER 1
GBE staff in association with other scientists published their research titled “Prediction of Y
chromosome haplogroups in human population living in Bosnia and Herzegovina”.

24 POSTER 2
The fact is that genetics and genetic predispositions play an important role in resistance and
response of one individuum to a certain disease.

26 THE 9 GREATEST GENETICISTS

List of the Greatest Minds of All Time, throughout history, in the field of genetics who have
»» p.8 made notable contributions to genetics with photos, bios, and other information.

BurchGene Magazine | December 2016

 4 P o p ular Topics in Genetic s
IS DNA THE FUTURE
O F D ATA S T O R A G E ?
    COMPUTATIONAL BIOLOGY               
The DNA molecule in our
cells carries genes which code and
produce all types of proteins and
enzymes responsible for carrying
out all cell functions in addition to
identify organism’s physical char-
acteristics. In addition, DNA mol-
ecule has an important applications
in forensic science, bioinformatics,
molecular biology, etc.
Scientists know a lot about
DNA’s functions, and it is not a
surprise that they can implement
its great benefits in different sci-
entific areas. However, the situa-
tion was different when we heard
that DNA would be implemented
in data storage.
However, using DNA mole-
cules as a storage medium is not
a new idea in the scientific com-
munity. The general idea about
the possibility of storing informa-
tion on DNA molecules were orig-
inally made by Mikhail Neiman
and published in 1964–65 in the
Figure 1: DNA can be used as a data storage medium
BurchGene Magazine | December 2016
Radiotekhnika journal, USSR.
On August 16, 2012, research
was published in the journal
Science by George Church and
colleagues at Harvard University,
in which DNA was encoded with
digital information that included
an HTML draft of a 53,400
word book written by the lead
researcher, eleven JPG images and
one JavaScript program. Multiple
copies for redundancy were added
and 5.5 petabits can be stored in
each cubic millimetre of DNA.
This research result showed that
DNA can be another type of storage
medium such as hard drives and
magnetic tapes.
Researchers started with digital
version of the book. Next, on paper,
they translated the zeros into either
the A or C of the DNA base pairs,
and the ones into either the G or T.
Then, using specific standard lab-
oratory techniques, they created
short strands of actual DNA that
Layla Abdel-Ilah
held the coded sequence—almost
55,000 strands in all. Each strand
contained a portion of the text and
an address that identified the loca-
tion in the flow of the book. In that
form, millions or even billions
copies of the book could fit easily
into a test tube and, under normal
conditions, last for very long years.
In January of 2013, researchers
from the European Bioinformatics
Institute (EBI) reported an
improved system in Nature at the
same time as Churce and colleagues
(2013). The article was submit-
ted at around the same time as the
paper of Church and colleagues.
Over five million bits of data con-
sisting of text files and audio files
were successfully stored and then
perfectly retrieved and reproduced
with accuracy between 99.99%
and 100%. The costs per mega-
byte were estimated at $12,400 to
encode data and $220 for retrieval.
In May of 2016, PRI news

Our DNA molecule is very suitable for
data storage purposes because it is:
1. Very small and dense: 1 kg of DNA
is enough to store all the data avail-
able in the world, we can just get a lot
of information into a very small space.
2. Can last for a long years in a good
condition particularly when kept cool
and dry: we can retrieve DNA from
very old, hundred-thousand-year-old
fossils.
3. Very interesting for us: it contains
our genetic material so we will keep
searching and discovering more and
more about it.
published that Microsoft and team
of researchers from University of
Washington have been preparing
DNA containing digital data for
sequencing, which allows them to
read and retrieve the original files.
The team was able to store 150
kilobytes on a strand of DNA.
The DNA molecule in our
living cells is very small and dense
which allow us storing all the data
available in the world in 1 kg of
DNA. DNA, especially if kept cool
and dry, has the ability to remain
intact for many years, and thereby
enable the retrieval of molecules
that are hundreds to thousands of
years old. Moreover, our genetic
material is very interesting for us
all the time so we will keep search-
ing and discovering more and more
about it.
Figure 2: Nitrogen bases sequence is available in form of binary
number
Popular Topic s in Ge ne t ic s
Figure 3: Storing a movie onto a DNA
DNA strand contains a phos-
phate group, a sugar group, and a
nitrogen base. There are four nitro-
gen bases, namely (A)denine, (T)
hymine, (G)uanine and (C)ytosine.
The sequence of base is a kind of
genetic code that is passed from
one generation to the next one.
Oligonucleotides are short DNA
molecules, these small bits of
nucleic acids can be synthesized in
the laboratory as single strand mol-
ecule with any original sequence.
Storing data is an essential
DNA function. In fact, much before
the advent of semiconductors, DNA
has been carrying genetic data for
generations, but the difference is
in the format of data. DNA carries
data in form of sequence of nitro-
gen bases, for example, GTACCG,
whereas semiconductors carry
data in form of binary digits, for
BurchGene Magazine | December 2016
5
example, 100101.
Assume we want to store an
image in one DNA strand. The
image is broken down into pixels.
The brightness value of each pixel,
available in form of binary number
is uniquely mapped to nitrogen
bases sequence, for example,
11010 is mapped to GATCAG.
Once the map is ready, DNA is
artificially synthesized in a labo-
ratory. Once synthesized, DNA can
be stored in test tubes for a long
years, hundreds or even thousands.
When we wish to retrieve the data
we just have to read the synthe-
sized DNA using a DNA sequenc-
ing techniques. This process will
generate the exact sequence of base
pair, which can be turned back into
binary data and, in turn, the image
can be regenerated.
The issue is not how much
data we can store, but is how to
manage all that data, know what
we have and where it is, and ensure
that it is in a retrievable form. We
are going to have to overcome all
the management and administra-
tive hurdles.
The largest obstacle to making
DNA data storage useful is the cost,
because you need to store some-
thing cheaper than one tape, other-
wise, no one will buy it. However,
that may no longer be the case in
another 10 years, as technology
gets cheaper and faster. Beyond
that, it will only be a matter of time
before you will make the decision
on where to store your library of
photos, books, or videos: an exter-
nal hard drive, or a strand of DNA.
 6 P o p ular Topics in Genetic s
LUIS AND REINHARD
REVEAL THEIR SECRETS
ABOUT DNA STORAGE
    INTERVIEW                        
To better understand work of
scientist with DNA as a memory
storage, we spoke with Luis
Henrique Ceze, an University of
Washington associate professor of
computer science and engineer-
ing and the university’s principal
researcher on the project. About
starting research on DNA he said:
„I’ve had a side interested in DNA
computing for a while, and while
on sabbatical in 2013 I head about
Nick Goldman’s work and got
immediately interesting in explor-
ing what a whole end-to-end would
look like. At that time my collab-
orators Karin Strauss and Georg
Seelig also got interested and we
put a research program together.“
We know that 0s and 1s as
a binary code are used in data
storage, so how can we encode
them in A, T, C and G?
“First you need to break the
information into units that would
fit in a molecule of about 100-200
nucleotides. Then you map groups
of 0s and 1s into ACGTs in a way
that avoids too many repeated
letters (like AAAA would be bad).
This way, say a movie, would be
mapped to a large collection of
these molecules.”
What are main challenges in
using DNA storage as a common
tool in everyday life?
“DNA synthesis still needs to
get much cheaper and much faster
to be competitive.”
BurchGene Magazine | December 2016
            
What methods are used in
storing and reading of DNA?
“DNA synthesis is used
to make DNA molecules that
encode information (the “write”
process). DNA sequencing is
used to read the composition
of the molecules that are then
decoded back to digital data.”
Regarding the cost and
realistic expectation for com-
plete data storage in DNA
molecule, professor Ceze con-
cluded that it would have cost
about $10 million to sequence
a human genome in 2007 but
close to only $1,000 in 2015, so
we can expect similar reduce in
cost with the storage of data in
DNA due to technology devel-
opment. In his opinion, it would
take around a decade for DNA
Figure 4: Luis Ceze, University of Washing- molecule to completely substi-
ton associate professor of computer science tute classical devices used in data
It is predicted that all digital storage.
data worldwide will grow to over
16 zettabytes in 2017. Can DNA be Another scientist that spoke with
possible solution to this problem? us about DNA storage is Reinhard
Heckel, Dr. sc. techn., postdoc-
Yes certainly, especially for toral researcher at the Department
archival storage that is not accessed of Electrical Engineering and
very frequently. Computer Sciences, University
of California, Berkeley. He is a
What is current capacity of person that dealing with machine
DNA molecule in storage, how learning, mathematical signal pro-
much data can we store inside of it? cessing and above all computa-
tional biology. His interes in appli-
We estimate that we can fit cations in genomics and biology,
about 1 exabyte (~10^18) in about arises from believe that there are
1 cubic inch. important problems in those areas
and algorithmic and statistical

Figure 5: Reinhard Heckel, Dr. sc. techn., postdoctoral
researcher at the Department of Electrical Engineer-
ing and Computer Sciences, University of California,
Berkeley
ideas are crucial for addressing
those problems.
Why do you think that
the storage of data in DNA is
impressive?
“DNA is considered an attrac-
tive future storage medium due to
its longevity and high informa-
tion density. More important for
storage than its density is perhaps
its longevity: As our experimen-
tal results demonstrate, it is pos-
sible to recover information from
DNA even after thousands of
years. Therefore, DNA has poten-
tial applications in future long term
storage.”
Can we use some other mole-
cules beside DNA as a data storage
system?
“In principle, yes. One of the
reasons that DNA is a natural
choice is that there are already
technologies available that can
write and read DNA.”
What is the advantage of DNA
data storage over standard data
storage devices?
“The main advantage over con-
ventional data storage devices is its
Popular Topic s in Ge ne t ic s
longevity: Disks, flash,
and tape in its current
design cannot store
information for more
than say a few decades.
In contrast, DNA can
serve an essentially
permanent storage
medium, which makes
it attractive for archi-
val applications.”
DNA can stay
stable in fossils for a
long time and envi-
ronmental condi-
tions influences it
vastly. What can we
do to protect DNA
from environmental
stresses?
“It is essential for
DNA data storage to
protect the DNA physi-
cally as well as information the-
oretically. My colleague Robert
Grass from ETH Zurich devel-
oped a technology for encapsulat-
ing DNA in Silica. This technol-
ogy allows to physically protect
the DNA in a similar way than
fossils do in nature. Additionally,
we protect the information theoret-
ically by adding redundancy to the
information that we want to store.”
What is the current capacity of
a DNA molecule in storage, and
how much data can we store inside
of it?
“A loose lower bound on the
capacity is two bits per nucleotide.
However, this capacity cannot be
achieved as errors on the nucle-
otide level occur and one has to
account for those. Additionally,
entire fragments of DNA do get
lost. The capacity we achieved was
1.187 bits per nucleotide.”
The story does not end once the
data is inside of the DNA. How do
you read this data? Are there any
difficulties with it?
“There are several technologies
for reading (sequencing) DNA,
we used an Illumina sequencer,
BurchGene Magazine | December 2016
7
however other techniques exists
and can be used.
There are several difficulties
with reading the DNA, the main
issue is that the reading process is
not error free and additionally takes
time. However, a large number of
reading errors are much less of a
problem in DNA data storage than
in biological and medical appli-
cations, as we can account for
those with error correcting codes.
Another difficulty is that typically
not all sequences are read, but
again we can account for this by
using error correcting codes.“
You developed a scheme to
correct errors in reading data based
on the Reed-Solomon Codes. Can
you explain how it works?
“In a nutshell, error cor-
recting codes (such as Reed-
Solomon Codes) add redundancy
to the data, and therefore allow
to correct errors, no matter where
the errors occur. To illustrate the
idea one can think about the sim-
plest code, which is a repetition
code. Specifically, if we want to
send a word, say ``DNA’’, we can
simply transmit it several times,
e.g., send ``DNADNADNA’’. If
one error occurs, say we receive
``DNADNADNZ’’, we can still
decode the original informa-
tion ``DNA’’ from the corrupted
message. However, a repetition
code is not a good code as it adds
a lot of redundancy for the number
of errors that it can correct. Coding
theory is about finding an optimal
tradeoff between the number of
errors that can be corrected and
the redundancy that is added.
Moreover, coding theory addresses
the computationally efficient recon-
struction of the information.
In DNA data storage, the
information is stored on several,
non-connnected, strands of DNA.
Errors occur in individual
sequences, and additionally whole
sequences get lost.
We developed a code that is
capable of correcting errors in
single nucleotides, and additionally
allows to recover entire sequences
that are lost.”
 8 P o p ular Topics in Genetic s

The „Gold Model“

for most microbiologi-
cal examinations is the
study of microorganisms
in pure culture or the
aqueous planktonic phase.
However, the paradigm
about planktonic bacterial
cells does not reflect the
real growth of bacteria in
nature. Hence, during the
last decade many studies
were directed towards the
understanding of bacterial
growth in natural condi-
tions. From these studies it
is clear that many bacteria
exist as part of a complex
association attached to the
surfaces and embedded
in their own extracellular
matrix. Today, such asso-
ciations are more com-
monly known as biofilms.

BurchGene Magazine | December 2016

 Popular Topic s in Ge ne t ic s
BIOFILMS
Mirsada Hukić & Monia Avdić Ibrišimović
    BASICS                                    
Biofilms represent associations of micro-
organisms which are irreversibly con-
nected to the surfaces by the production
of a extracellular polymer substance
(EPS) and at the same time show changed
characteristics (phenotype), compared to
the corresponding planktonic cells. EPS
is a highly dehydrated and chemically
complex matrix which has the aim to
store nutrients and at the same time can
trap other microbes as well as non-cel-
lular material like minerals, crystals
and corrosion products. Inside a biofilm
cells function coordinately as a cooper-
ative consortium, in a way mimicking a
multicellular organism. The process of
developing this complex and highly dif-
ferentiated association from single cells
demands complex genetic regulation.
The formation of biofilms occurs in
several consecutive phases. In the first
phase an initial transport and reversible
attachment of bacteria to the surface, with
adsorbed organic and inorganic nutri-
ents, takes place. Subsequently EPS gets
secreted and it forms bridges between
individual cells, which results in the irre-
versible attachment or „cementing“ of the
cells to the surface. The last phase, in the
formation of a biofilm, is the coloniza-
tion of the surface. Bacteria, which are
attached to the surface, grow and divide
and by doing so create micro-colonies,
which are regarded as the elemental orga-
nization units of biofilms. The “primary
colonizer“ secrets substances which
attract other planktonic bacteria that
are found in the environment (second-
ary colonization). A completed biofilm
has complex architecture and is made
out of bacteria embedded in EPS coated
micro-colonies, between which there are
less dense parts of the matrix with perme-
able water channels that aid in the trans-
port of nutrients and waste products.
The colonization of surfaces and sub-
sequent formation of biofilms is best
studied in bacteria, although fungi,
algae, protozoa and viruses have been
isolated from biofilms in the industrial
and medical setting. Biofilms can form
on almost all surfaces in the environment,
BurchGene Magazine | December 2016
9
regardlessweather the material is natural
(plant and animal) or synthetic (medical
indwelling device and industrial surface).
In humans biofilms can have a protec-
tive role. For example the gut commensal
flora forms biofilms which are attached
to epithelial cells, making a barrier which
prevents the penetration of pathogens.
Dental plaque is made out of different
bacterial biofilms, but the decline of
teeth is a consequence of proliferation of
pathogenic strains in the same. Although
biofilms are ubiquitous in nature, their
significance in the clinical setting is often
underestimated. Today biofilms represent
a severe source of infection, especially in
immune-compromised individuals with
indwelling medical devices (like cath-
eters). This has serious clinical conse-
quences and is the cause of many per-
sistent and chronic infections. Thereby
one should have in mind that bacteria
inside a biofilm are embedded inside EPS
which provides them protection from the
hosts immune response as well as anti-
microbial remedies. Infections caused
by biofilms often have recurring symp-
toms until the source of the infection is
not removed surgically. In opportunis-
tic pathogens, like Staphylococcus epi-
dermidis, the ability to form biofilms is
considered a factor of virulence and so
commensal bacteria become a severe
source of infection in the hospital envi-
ronment. Today numerous studies con-
firmed that the rates of horizontal gene
transfer are elevated in biofilms com-
pared to planktonic bacteria. Inside bio-
films horizontal gene transfer is responsi-
ble for the appearance of antibiotic resis-
tance which can pass from commensal to
pathogenic bacteria. It is considered that
the “notorious MRSA” gained the mecA
gene, which is responsible for the resis-
tance to methicillin, through horizontal
gene transfer.
Accordingly biofilms are considered
the next great challenge for microbiol-
ogists and clinicians especially taking
into account their high rates of resistance
towards antibiotics which makes them
very difficult to treat.
 10 P o p ular Topics in Genetic s

STEM CELL
RESEARCH
Mike Byrom and Adna Ćuk
    TISSUE ENGINEERING                                   

Regenerative medicine is a branch of tissue engineering and molecular biology which deals
with the process of reparing and recovering human cells and tissue, returning them into normal
state This makes them subsequently able to function properly as any normal cell never being
engineered. However, the best application of regenerative medicine could be considered from
the aspect and very interesting scientific topic related to stem cells. These are cells which can be isolated from
our body, then be engineered by various methods, and afterwards introduced into our body by different ways
such as: injections of stem cells through cell therapy, induction of regen-eration by biologically active substances
or by transplantation into organs and tissues.
Beginning with some future capabilities of stem cells, then moving to their basics, their different types and also
emphasizing the main differences between them; subsequently discussing embryonic and adult stem cells with
the special attention to multipotent stem cells and their usage nowadays; and afterwards providing some basic
steps regarding the maintenance of stem cells in laboratory conditions, this article could be considered as very
informative for every reader. Finally, at the very end there are answers on the most frequently asked questions
about stem cells provided in this article.

Stem cells are one of the most
important medical discoveries of
our lifetime. They, as a class of
medicine, have almost limitless
potential to treat disease and to
improve the quality of our lives.
Many thousands of researchers
worldwide continually work to
better understand how these cells
function and how we can utilize
them to benefit mankind. The
ability to grow your own tissue
for transplant and the ability to
regenerate or grow replacement
organs is not just a pipe dream but
an achievable goal Actually, there
is an obvious need to draw atten-
tion of all medical profession-
als and members of our audience
who are grounded in practicality
and tend to be a little more skep-
tical to the example of amazing
development of a modern mobile
phone. The “Communicator” was
first introduced into modern culture
in 1964 on the television show
BurchGene Magazine | December 2016
Star Trek. It was a fictional hand highly controversial for moral and
held device that could communi- ethical reasons that will not be dis-
cate instantly over vast distances cussed here. Perhaps the biggest
without the use of wires. The first scientific problem is the nature of
iPhone was released only 46 years the cells themselves. These cells
later and it shares startling similar- are responsible for producing the
ity to that original fictional device.
Technology is moving faster today
than ever before and it is evident
that the ability to repair damaged
organs and replace diseased body
parts will be possible and it will
almost assuredly be in the lifetimes
of our children.
There are different classes of
stem cells. Almost everyone has
heard of embryonic stem cells.
These cells are classified as “plu-
ripotent” which means they have
the ability to form every type of
tissue in the body. This ability to
form all tissues gives them great
potential. However there are a
few problems with using them for
medical treatment. These cells are Figure 1: Stem cells help treat disease
and thereby improve the lives of many
 Popular Topic s in Ge ne t ic s 11

One question There is one very

The requirements for a successful storage of stem cells are: frequently asked question: How
long can the sample be stored?”.
* The identity of the donor must be clearly established. The answer is that all biologi-
cal activity stops at temperatures
* The donor must test negative for a panel of infectious diseases as below -135°C. Storing the mate-
outlined by the regulatory authorities in each country. rial at temperatures colder than this
effectively stops the aging process
* The cells must be free of microbial contamination. and keeps them in suspended ani-
mation where they can remain for
* The cells must exhibit cellular morphology and growth character- an indefinite period of time. We
istics consistent with MSC’s. advertise that we will store samples
for the lifetime of the donor and
* The final product must be functionally capable of differentiating there is ample scientific evidence
into bone, cartilage and fat tissue. to support this statement. There are
many documented and published
* There must be a minimum of 800k cells present that meet the above cases of cells being stored for more
criteria within the 21-day purification process. than 50 years without any loss of
functionality.
entire body during embryogene- means the same, so there is no need Another frequently asked
sis and can only be found during for one of these two words. In addi- question is: “what happens if the
this short window of your lifetime. tion to being able to produce many electricity goes out?” The use of
They are activated and deactivated different types of tissues they can nitrogen instead of a mechanical
by chemical signals at exact times also be isolated and cultivated in freezer removes the dependency
as directed by their environment. a laboratory setting to a relatively on electricity. There are no electri-
This highly regulated environment, large number without reducing cal requirements for the storage of
also called the womb, is responsi- their functionality. These cultivated samples because the temperature is
ble for controlling the growth and cells DO NOT form tumors when a physical property of that element.
function of these cells. When you injected into the body. This means In short, the power can go out and
take ES cells out of this regulated that they can be used safely in a it will not affect the samples.
environment and put them into a therapeutic setting. The ability to Finally, there is one more not
non-regulated environment such as form many tissues when coupled infrequently asked question about
your knee they will grow without with the ability to be cultivated stem cells: “Why cannot people
restriction and form tumors very and safely delivered makes them just wait until they need these cells
similar to a cancer. This makes the most useful type of adult stem and then obtain the material for
them unsuitable for human therapy. cell known. therapy”? The reason is that stem
The samples that meet the cells age just like we age. They are
There is another class of stem storage requirements are then cryo- exposed to pollution, toxins, and
cells called adult stem cells. Adult preserved at extremely cold tem- radiation from the environment and
stem cells can be found in differ- peratures by a very specialized all of this reduces their usefulness.
ent tissues of the body. They are no process. The cells are stored at The MSC’s from a 5 year old are
moral or ethical issues with obtain- -196°C in the vapor phase of liquid significantly better than the MSC’s
ing or using them. Some types, but nitrogen. Storing the material in the from a 50 year old. You need these
not all types, do have scientific vapor phase of liquid nitrogen pre- cells to be in an extremely young
issues that limit their usefulness vents the possibility of cross con- and pristine state for the best ther-
since there is a huge number of dif- tamination between patients during apeutic results.
ferent types of adult stem cells each storage.
with different properties, provided
is a brief description of, perhaps,
the most important and interesting
one. Namely, one type of adult stem
cell is named Mesenchymal stem
cells, abbreviated as MSC’s and are
classified as “multipotent”. This
means that they can form many
but not all types of tissue found in
the body. They are well known to
be able to produce muscle, bone,
cartilage, fat, liver, insulin secret-
ing cells, and many other types of
tissue. Each and every actually Figure 2: Types of stem cells

BurchGene Magazine | December 2016

 12 P o p ular Topics in Genetic s

Nermin Đuzić

Over the last few years, prominent professors and hardworking students from Burch University participa-
ted in many local and international conferences related to the field of genetics and bioengineering. These
conferences contributed primarily to raising awareness of people about significance and improvement of
different branches of bioengineering and their implementation in the most popular natural sciences nowa-
days (i.e. medicine, biochemistry, bionics, nanotechnology, biotechnology etc.) and agricultural sector of
our country as well. It is evident that they gained a lot of experience, adopted new ideas and approaches
and broadened their vision and knowledge. We can say that it is a great honor to have such amazing pro-
fessors and colleagues sitting next to us. The primary goal of this article is to give you a brief overview
of some of the most important conferences and scientific events where our professors and students took
participation. Beside many conferences held in our country, there are also some of the most important
conferences in other countries like neighboring Croatia and Montenegro and also in more distant coun-
tries like China and Cyprus. There is no doubt that all these conferences are increasing the rating, not
only of the GBE department of our University, but also of the whole Burch family, which can be seen
in the continuous development and progress. Reading this article, you will get familiar with interesting
topics, famous speakers and innovative ideas that may help you in your future work and career.

Let’s start with “The Second Symposium of Geneticists in

Bosnia and Herzegovina”, which was held on the 2nd and
3rd October 2015 in the amphitheater of Faculty of Medi-
cine in Banja Luka and organized by Association of Gene-
ticists in Bosnia and Herzegovina and Institute for Genetic The Second Symposium
Engineering and Biotechnology. Among many oral and of Geneticists in Bosnia
also poster presentations, participation in this Symposium and Herzegovina
took 4 people from our University, Professor Dr. Mirsada
Hukić, Prof. Dr. Monia Avdić-Ibrišimović and two studen-
ts, Adnan Fojnica and Ahmed Osmanović, with a Review
Article: CEBPA gene.

We are glad to publish and share that professor Dr. Damir

Marjanović, the former head of our department and current
Rector of our University was a keynote speaker at the 4th
International Conference on Genomics 2015 (ICG2015),
which was held in Xi’an, China from 23rd to 25th Octo- 4th International Con-
ber, where he presented his work on Forensic Genomics. ference on Genomics
The three-day conference was organized by Genetics So- 2015(ICG2015)
ciety of China, Chinese Academy of Sciences and Xi’an
Jiaotong University and was focused on “Beyond Biologi-
cal and Medical Big Data”, comprising, besides Forensic
Genomics, also Marine Genomics, Epigenetics and Tran-
scriptional regulation and Genomics and Big Data.

BurchGene Magazine | December 2016

 Popular Topic s in Ge ne t ic s 13

From the 29th until 31st October 2015, Sarajevo was the
host of the XXV International Conference on Infor-
ma¬tion, communication and automation technologies
(ICAT 2015), whose organizers had an opportunity to wel-
come researchers and scientists from the whole world. In XXV International Con-
the crowded amphitheater at Faculty of Electrical Engine- ference on Information,
ering , participation with their work “Software Package for communication and
Tracking Status of Inspection Dates and Reports of Medical automation technolo-
Devices in Healthcare Institutions of Bosnia and Herzego- gies (ICAT 2015)
vina“ took following professors and students from our Uni-
versity: Gurbeta Lejla, Badnjević Almir, Pinjo Nejra and
Ljumić Fahira.

Next important event we are going to talk about is the In-

ternational Congress of students and young doctors of (bio)
medicine in Bosnia and Herzegovina “MEDICON”, that
was held at Medical Faculty in Tuzla from the 30th October
to 1st November 2015. This Congress was a great opportu- International Congress
nity for students and young doctors to broaden their hori- of students and young
zons and improve their knowledge in medicine and related doctors of (bio)medici-
scientific fields. Participation had been taken also by our ne in Bosnia and Herze-
students Ahmed Osmanović and Adnan Fojnica and their govina “MEDICON”
mentor Prof. Dr. Damir Marjanović with a poster-presenta-
tion on the topic: Genetic predisposition to a heart disease.

Now it’s time to move on conferences from this year.

First such conference worth attention is XIV Mediterra-
nean Conference on Medical and Biological Engineering
and Computing (MEDICON 2016), held from 31st March
until 2nd April 2016 in Paphos (Cyprus). The event was XIV Mediterranean Con-
organized by University of Cyprus, IFMBE and other in- ference on Medical and
stitutions. “Software Solution for Tracking Inspection Pro- Biological Engineering
cesses of Medical Devices from Legal Metrology System“ and Computing (MEDI-
is the title of work done by two professors from our Burch CON 2016)
University: Almir Badnjević and Lejla Gurbeta; and fol-
lowing students: Sejdinović Dijana, Alić Berina and Ab-
del-llah Layla.

We are proud to have an opportunity to share information

that our professor doc. Dr. sci. Almir Badnjević, current
head of our Department, and assistant Lejla Gurbeta were
participants on the 39th international convention on infor-
mation and communication technology, electronics and 39th international con-
microelectronics (MIPRO 2016) situated in Opatija, Croa- vention on information
tia from 30th May until 3rd June this year, where main ICT and communication
trends in industry, education, science and local govern- technology, electronics
ment are presented. Joyfully, our professor Almir claimed: and microelectronics
As a member of the Program Committee and co-author of (MIPRO 2016)
3 papers, it was a big honor for me to be one of 1200 accre-
dited participants from 30 countries.

BurchGene Magazine | December 2016

 14 P o p ular Topics in Genetic s

The team consisted of three members from our depart-

ment, Prof. Dr. Damir Marjanović and Senior Teaching
Assistants Larisa Bešić and Adna Ašić, took a partici-
pation in International Union of Anthropological and
Ethnological Sciences’s (IUAES) Inter-Congress, that
was organized in Dubrovnik, Croatia, from 4th un- International Union of
til 9th of May, 2016. After Prof. Marjanović’s speech Anthropological and
about “Applied molecular anthropology: Retrospective Ethnological Sciences’s
and perspective,” our assistants presented two research (IUAES) Inter-Congress
works, namely “Turkish population currently residing
in Sarajevo, Bosnia and Herzegovina – A synopsis of
population genetics studies” and “Prediction of Y haplo-
groups in Bosnian and Herzegovinian population based
on 23 Y-STR loci “.

Last conference worth mentioning was held from 12th

to 16th June in Bar, Montenegro and was named as the
5th Mediterranean Conference on Embedded Computing
(MECO 2016). MECO 2016 provided an ideal opportu-
nity for young scientists and engineers to exchange new 5th Mediterranean
ideas in many important technological areas. Among 115 Conference on Embed-
papers submitted from 25 countries all over the world, ded Computing
following students took participation: Adnan Fojnica, (MECO 2016)
Ahmed Osmanovic, Dijana Sejdinovic, Berina Alic, Sa-
bina Halilovic, Halida Avdihodzic, and Almir Aljovic,
while our professor Dr. Almir Badnjevic was invited
speaker and the Chair of Editorial Committee.

There is no doubt that these interactive conferences are great and unique opportunity not only for profes-
sors, but also for students to exchange their ideas and experiences with others, to improve and raise their
knowledge but also to meet new people in the same branches. Currently, students and professors are also
actively participating in organizing the 2nd International Conference on Medical and Biological Engine-
ering that will be held in Sarajevo in March 2017. This is exciting, informative conference with the goal
of sharing ideas and best practices in biomedical engineering and related fields. Let’s recall that The 1st
Conference of Medical and Biological Engineering in Bosnia and Herzegovina (CMBEBIH 2015) was
successfully held from 13th to 15th March 2015 and organized by the Bosnia and Herzegovi-na Medical
and Biological Engineering Society. Therefore, we are warmly inviting and suggesting you to come and
experience “Pursuing innovation. Shaping the future”. This is a chance that you shouldn’t miss.

Don’t miss #cmbebih2017!

BurchGene Magazine | December 2016

 Popular Topic s in Ge ne t ic s 15

THANKS TO OUR SPONSORS

SomnaCare
Prvi privatni centar za poremećaje
spavanja u Bosni i Hercegovini

KONTAKT
Branilaca Šipa 20, 71000 Sarajevo
Bosna i Hercegovina
Mobitel: +387(0)61 717 692
Email: info@somnacare.org

Mikrobiologija
NALAZ pruža usluge iz oblasti biohemije, imunologije, mikrobiologije.

KONTAKT
Hasana Brkića 2 (Shoping centar Grbavica)
71000 Sarajevo, Bosna i Hercegovina
Phone: +387 33 651 371
Email: info@nalaz.org
Web: NALAZ.ORG

BurchGene Magazine | December 2016

16 P o p ular Topics in Genetic s
I N F O G A L L E RY
    DNA UNDERSTANDING                    
G
enome is the complete
genetic or DNA comple-
ment of an organism. It includes
the genetic material of the nucleus
and cytoplasm. All organisms have
a genome made up of DNA, con-
taining genes. Genomes may vary
in their size, number of genes,
number of chromosomes, and how
genes are organized within chro-
mosome(s), and the DNA may be
circular or linear. A given organ-
ism has only one genome regard-
less of whether the organism is
haploid, diploid, or polyploid. The
term was originally used to denote
one haploid set of chromosomes in
a eukaryote organism. The genome
projects are having a profound
impact on health-care discoveries.
The main purpose of genome proj-
ects is to access the entire genome
sequences that can be used to find
out the probable genes and their
functions in various organisms.
Some important genomes that are
partially or completely sequenced
include that of e.coli,, yeast, arabi-
dopsis, drosophila, mice, humans,
rice,etc.
BurchGene Magazine | December 2016
DNA
C hromosome is a structure
composed of a very long
molecule of DNA and associ-
ated proteins (e.g. histones) that
carries hereditary information.
Chromosomes are especially evi-
dent in plant or animal cells under-
going mitosis or meiosis, where
each chromosome becomes con-
densed into a compact, readily vis-
ible thread. In nondividing cells
chromosomes typically assume a
more dispersed form called chro-
matin. The number of chromo-
somes is characteristic for the spe-
cies concerned. In a bacterium only
one chromosome is evident as the
cell is about to divide. After DNA
replication, the two new chromo-
somes attach to a specialized site
on the bacterial plasma membrane
for segregation to the two daugh-
ter cells.
BurchGene Club
E
ach duplicated chromosome
has two sister chromatids,
which are joined coppies of the
original chromosome. The two
chromatids, each containing an
identical DNA molecule, are ini-
tially attached all along their leng-
hts by protein complexes called
cohesins; this attachment is known
as sister chromatid cohesion. Each
sister chromatid has a centromere,
a region of the chromosomal DNA
where the chromatid is attached
most closely to its sister chroma-
tid. This attachment is mediated
by proteins bound to the centro-
meric DNA; other bound proteins
condense the DNA, giving the
duplicated chromosome a narrow
„waist“. The portion of a chromatid
to either side of the centromere is
referred to as an arm of the chro-
matid. Later in a cell division pro-
cess, the two sister chromatids of
each duplicated chromosome sepa-
rate and move into the new nuclei,
one forming at each end of a cell.

D N
NA-looping mechanisms
are part of networks that
regulate all aspects of DNA metab-
olism, including transcription, rep-
lication, and recombination. DNA
loop formation may have different
functions in different cellular con-
texts; in some cases, the loop itself
is requisite for regulation, while in
others the increase in the effec-
tive local concentration of pro-
tein may account for the effects
observed. The ability of DNA to
form loops is affected by the dis-
tance between binding sites; by the
DNA sequence, which determines
deformability and bendability; and
by the presence of other proteins
that exert an influence on the con-
formation of a particular sequence.
D
NA eukaryotic cells is unit of heredity.
packed by association with
specific proteins such as the his-
tones into a structure known as
chromatin. The fundamental unit
of this structure is the nucleosome
in which the DNA is wrapped twice
around a unit of eight histone mol-
ecules. This structure is compacted
further into the so-called solenoid
structure in genes that are not tran-
scriptionally active or about to
become active. The tightly packed
solenoid structure can be com-
pacted even further, by extensive
looping, to form the chromosomes
that are visible during cell division.
Popular Topic s in Ge ne t ic s 17
N ucleosome a particle that
forms the primary pack-
ing unit of DNA in chromatin.
Nucleosomes give electron micro-
graphs of decondensed chromatin
a ‘beads-on-a-string’ appearance,
and are released on mild digestion
of eukaryotic nuclei with micro-
coccal endonuclease. Each consists
of a segment of duplex DNA, 160-
240 base pairs long, with associ-
ated histone; about 146 base pairs
of the DNA comprise a core par- ucleotide is one of the struc-
ticle and the remainder form the tural components, or build-
linker DNA. ing blocks, of DNA and RNA. A
nucleotide consists of a base (one
of four chemicals: adenine, thy-
mine, guanine, and cytosine) plus a
molecule of sugar and one of phos-
phoric acid.C, T, and U are called
pyrimidines and each has a single
nitrogen-containing ring. A and G
are called purines and each has two
nitrogen-containing rings.
D
NA or deoxyribonucleic
acid is an very important
molecule found in every living
organism. It’s responsible for
heredity – it carries, stores and
express hereditary material. DNA
is composed of four basic com-
ponents called nucleotides. Each
T
nucleotide is made up of phos-
phate group, sugar (deoxyribose he nucleic acid bases jut out
type) and one of four nitrogenous from the sugar phosphate
backbone and are free to form con-
bases ( adenine, guanine, thymine,
cytosine). DNA molecule is com-nections with other molecules. The
most stable structure occurs when
posed of two long chains (strands)
another single strand of nucleotides
in form of thin double felix. DNA
aligns with the first to form a dou-
contains the information (genes)
ble-stranded molecule, as seen in
that codes for proteins. The gene
the DNA double helix . Each base
is the basic physical and functional
forms hydrogen bonds to a base
in the other strand. There are two
types of bases in DNA: purines
(guanine and adenine) and pyrim-
idines (cytosine and thymine).
Each base pair consists of one
purine connected to a pyrimidine
via hydrogen bonds. Guanine pairs
only with cytosine (G-C) via three
hydrogen bonds. Adenine pairs
only with thymine (A-T) in DNA
or uracil (A-U) in RNA. Because
an adenine-thymine (A-T) or ade-
nine-uracil (A-U) base pair is held
together with only two hydrogen
bonds, it requires less energy to
break the connection between the
bases than in a G-C pair.
BurchGene Magazine | December 2016
 18 P o p ular Topics in Genetic s

N U C L E A R G E N E S A S S O C I AT E D
WITH MITOCHONDRIAL
DISORDERS IN HUMANS

Dževida Tarakčija
    MOLECULAR GENETICS                                    
mitochondria are responsible for
mtDNA biosynthesis and mainte-
nance, for translation machinery of
mitochondria. They are involved in
mitochondrial dynamics, complex
assembly, CoQ10 (coenzyme Q10)
biosynthesis and indirectly affect-
ing OXPHOS function.

Mitochondrial disorders

Mitochondrial disorders are

regulated with mitochondrial
DNA and nuclear DNA. Over
the last few decades it is become
Figure 1: Organization of the mammalian mitochondrial genome (A)
obvious that correlation between
and the mitochondrial respiratory chain (B)
mitochondrial and nuclear genome
affects on mitochondrial disor-
Mitochondria are mem- 99% of proteins responsible for ders. Those mitochondrial dissor-
brane-bound organelles that are mitochondrial energetics, morphol- ders that are caused by mutation in
present in all nucleated cells. Their ogy and redox regulation. Nuclear genes encoded in nucleus become
primary function is to produce ATP genes encode some mitochondrial object of attention in recent years.
and to support aerobic respira- imported proteins, including com- Different expression of OXPHOS
tion by oxidative phosphorylation ponents of oxidative phosphoryla- has major impact on disease
(OXPHOS). Beside these func- tion complexes and factor associ- expression, because this system
tions, mitochondria are involved ated with replication, transcription, provides energy. Mitochondrial
in process of apoptosis, aging, assembly, function and turnover. In disorders of nuclear DNA origin
store calcium for cell activities, general, nuclear genes involved in primarily result from dysfunction
generate heat and mediate cell mitochondrial function can be clas- of the mitochondrial respiratory
growth. Shaped like an oval, its sified in two groups: structural and chain (RC) or ATP synthesis. These
size is 0.5 to 10uM. Furthermore, non-structural genes. Structural disorders can affect one organ or
it is inherited maternally and it is nuclear genes are involved in pro- more, but usually those organs
unique because it has own circu- duction of proteins that build com- depend on aerobic metabolism such
lar genome (mitochondrial-DNA) plexes of OXPHOS. The respira- as brain, heart, kidney and muscles.
which consist of 16 569 bp and it tory chain or oxidative phosphor- Mutations on structural and
is separated from nuclear genome. ylation system (Figure 1-B) con- non-structural nuclear genes could
MtDNA has 37 genes and encode sists of about 90 structural pro- lead to mitochondrial disorders,
for 22 tRNA, 2 rRNA and 13 pro- teins assembled into four com- such as Leigh syndrome, Lactic
teins (Figure 1-A). plexes (I-IV) and complex V which acidosis, Encephalomyopathy,
In spite of the fact that the mito- is ATP synthase. Seven subunits of Autosomal dominant paragangli-
chondrial and nuclear genomes are complex I, one subunit of complex oma, Spastic paraplegia, Cerebellar
physically separated, communica- III, three subunits of complex IV ataxia, Deafness. Table-1 sum-
tion between them is essential for and two subunits of complex V marize number of structural and
maintenance of normal function of are encoded by mitochondrial non-structural nuclear genes that
mitochondria. It is estimated that proteins. Non-structural nuclear affect those disorders.
nuclear-encoded genes account for genes which are connected with
BurchGene Magazine | December 2016
 Popular Topic s in Ge ne t ic s 19
Autosomal dominant Table 1: Mitochondrial disorders correlated with mutations found in nuclear genes
paraganglioma

The paraganglioma (PGL)

syndromes are autosomal dom-
inant disorders characterized by
familial predisposition to PGLs,
phaeochromocytomas (PCs),
renal cell cancers, gastrointesti-
nal stromal tumors and, rarely,
pituitary adenomas. Every disor-
der is connected with transforma-
tion in a gene encoding a specific
subunit of succinate dehydroge-
nase. Scientists have recognized
four types of inherited paragangli-
oma-pheochromocytoma, named
types 1 through 4. Every type is
recognized by its genetic cause.
Individuals with types 1, 2, and 3
commonly create paragangliomas
in the head or neck area. Hereditary
paraganglioma-pheochromocy-
toma is commonly diagnosed in a
man’s 30s. Symptoms of heredi-
tary paraganglioma are elevations
in blood pressure, headache, epi-
sodic profuse sweating, irregular
heartbeat, pallor, and apprehen-
sion or anxiety. Paragangliomas
are vascularized tumors that can
be benign, malignant, functional
or nonfunctional. The areas in
which paraganglioma can be
found is in the neck, head, pelvic
areas, thoracic and abdominal area.
Pheochromocytomas are catechol-
amine-secreting paragangliomas
found in the adrenal part and they
are also known as adrenal chro-
maffin tumors. Clinical features
of catecholamine excess include
hypertension, headache, sweat-
ing, palpitation. Burnichon et al,
(2009) reports that in the 2000. and
2001., genes that encode for three
subunits of the succinate dehydro-
genase enzyme (SDHD, SDHB
and SDHC genes) have major
effect for genetics of paragangli-
omas and pheochromosytomas.
Mutations in these genes result in
changing of succinate dehydro-
genase complex (complex II) of
OXPHOS. Mutations which are
summarized in Table-2 will result
in premature stop codon, trun-
cated protein or they are in highly
conserved regions. All of this will
affect the function of succinate
dehydrogenase complex leading
to mitochondrial non-function
and cause disorders. Hereditary
head and neck paragangliomas
(Figure-2) are tumors associated
with nervous system and muta-
tions found on genes have effect
on catalytic subunits of complex
II (flavoprotein and iron protein),
SDH enzyme activity and mito-
chondrial morphology.
Figure 2: representation of paragan-
glioma formed on the neck
SDHC and SDHD encode for
integral membrane-protein sub-
units. Mutations in all these genes
result in neoplasia which is the
formation or presence of a new,
abnormal growth of tissue. SDHD
is gene that encode for small
subunit of cytochrome b in suc-
ciate-ubiquinone oxidoreductase
(complex II) while SDHC code
for large subunit of cytochrome b
in succinate-ubiquinone oxidore-
ductase and they are connected to
type 1 and type 2 paraganglioma
Table 2: Mutation found in sturctual and non-structural nuclear
genes correlated with autosomal dominant paraganglioma
BurchGene Magazine | December 2016
respectively. Inactivation of SDHD
gene in patient with paraganglioma
is associated with the complete and
selective loss of complex II elec-
tron transfer activity and with loss
of the succinate dehydrogenase
(mediated step of the Krebs cycle).
Mitochondrial diseases are
extremely difficult to diagnose due
to extreme locus and allelic hetero-
geneity, with both nuclear and mito-
chondrial genes potentially respon-
sible. There are different types of
mutations such as insertion, dele-
tion, substitution, transition that
can lead to change of amino acid
and result in truncated protein or
complete loss of protein function.
So far, a number of mitochondrial
syndromes correlated with muta-
tions in nuclear genes are identi-
fied. Significant clinical variabil-
ity in individuals that do not fit per-
fectly into one particular syndrome
further complicates the diagnosis.
More research with focus on iden-
tification of nDNA and ntDNA
mutations that are associated with
particular mitochondrial disorder
and development of specific diag-
nostic assays are required. The era
of massively parallel sequencing
promises a faster pace of discov-
ering genes involved in mitochon-
drial biogenesis.
20 P o p ular Topics in Genetic s
m t D N A D I S EA SES – A STO RY
O F C R A F TY TRI CK STE RS
IN O U R CEL L S
    HUMAN GENETICS 
Interest in mitochondria and
their genome has blossomed over
the last few decades. As the gath-
ered knowledge expanded, the dis-
eases caused by mitochondrial dys-
functions have become an important
area of human pathology. Human
mitochondrial DNA (mtDNA) is
a small gene-rich, circular mole-
cule of 16,569 bp. Besides the 13
components of oxidative phosphor-
ylation, mtDNA encodes 2 ribo-
somal RNAs and 22 tRNAs. Those
rRNAs and tRNAs are necessary
for the synthesis of 13 polypeptides
in mitochondria and therefore crit-
ical for oxidative phosphorylation
process. In this article we will take
a look at rRNA and tRNA muta-
tions of mtDNA associated with
mitochondrial disease so far, and
we will try to provide a compre-
hensive overview of the research
and materials published on this
topic, and discuss the future direc-
tion of the research in this area. We
will begin with outlining the pecu-
liarities of mitochondrial genetics
and mtDNA – a humble molecule,
Figure 1: Human mitochondrial DNA map
BurchGene Magazine | December 2016
but a crafty trickster.
Mitochondrial DNA – a loop
with a twist
In evolutionary sense, mito-
chondria are generally consid-
ered to be remains of ancient bac-
terial symbionts, and as such they
are thought to have transferred the
majority of their genome to the host the RNA necessary for mtDNA
cell over time, facilitating creation translation: 2 rRNAs (12S and 16S)
of all contemporarily known nucle-
ated eukaryotic cells (Margulis,
1971). All that has remained is a
compact, app. 16,569 bp long, dou-
ble-stranded, circular DNA whose
complete sequence was fully elu-
cidated in 1981 and further revised
in 1999 (Tuppen et al., 2010). In
a single eukaryotic cell, several
hundreds or thousands of copies
of the mitochondrial genome are
present at any given time. A sit-
uation known as homoplasmy
prevails if all mtDNA molecules
present within a cell are identical.
However, the presence of two or
more mitochondrial genomes in which govern the clinical symp-
Jasin Hodžić
a cell is not an excludable situa-
tion, and such case is defined as
heteroplasmy.
Human mtDNA is strictly
inherited uniparentally, through
the maternal lineage, and contains
only 37 genes. These genes encode
13 polypeptides which are all core
subunits of respiratory chain com-
plexes I, III, IV, and V, as well as
and 22 tRNAs. Schematic over-
view of the structure of mtDNA
is shown on the Figure 1 below.
Human mtDNA genes contain no
introns and almost no intergenic
noncoding nucleotides, except the
1.1 kb displacement loop (D-loop),
which contains transcriptional pro-
moters, as well as at least one of the
proposed replication origins (OH)
(Figure 1).
Specific features of mtDNA
diseases
There is a number of features
toms onset, phenotypic variability,
and variable penetrance of mito-
chondrial diseases. These features
include the threshold effect, mitotic
segregation, clonal expansion, and
a genetic bottleneck.
(1) Threshold effect: Whilst
some deleterious mtDNA muta-
tions are homoplasmic, the vast
majority of such mutations are
found in some and not all genomes.
In cases of heteroplasmy, the onset
of clinical symptoms is determined
by the ratio of wild-type to mutant

mtDNA. Biochemical defects
and tissue dysfunction become
apparent only after the necessary
minimum critical proportion of
mutated mtDNAs is present. The
value of threshold is typically in
the range of 60%–90% mutant to
wild-type mtDNA.
(2) Mitotic (vegetative) seg-
regation: Mitochondria are ran-
domly segregated during mitosis.
The proportion of mutant mtDNA
in the daughter cells can thus shift
in heteroplasmic cells. In cases of
mutant load exceeding the patho-
genic threshold for that tissue, clin-
ical expression of the disease can
occur, as discussed in the previous
section, and shown in Figure 2.
(3) Clonal expansion: Clonal
expansion is defined as the pref-
erential amplification of mtDNA
mutations to a high level in
post-mitotic tissues. Such expan-
sion is considered to be a result of
random genetic drift, dependent
on relaxed replication of the mito-
chondrial genome (Elson et al.,
2001), as can be seen on Figure 2.
(4) Genetic bottleneck of
mtDNA: Heteroplasmic mtDNA
genotypes in mammals rapidly seg-
regate between generations. This
phenomenon, along with a return
to homoplasmy in some progeny,
strongly suggests the existence
of an mtDNA bottleneck during
development (Tuppen et al., 2010).
The exact mechanism by which this
genetic bottleneck occurs is cur-
rently subject of fierce debates. A
prevalent hypothesis states that this
bottleneck arises during embryonic
development, and that it is driven
by a marked reduction in mtDNA
copy number in the germ line (Cree
et al., 2008).
One of the key features of
Figure 2: Schematic overview of mitochon-
drial mitotic (vegetative) segregation and
relaxed replication phenomena.
Popular Topic s in Ge ne t ic s
Figure 3: Genotype to phenotype correlations in
certain human mitochondrial diseases
clinical syndromes associated with
mtDNA mutations is their extreme
variability. Furthermore, they can
manifest at any stage in life of
patients. The age of onset reflects
the level of mutation and the sever-
ity of the biochemical defect on
the whole. However, other factors
(such as nuclear genetic and envi-
ronmental factors) also have an
effect on the expression of disease
(Tuppen et al., 2010).
Current compendium of poly-
morphisms and mutations in human
mitochondrial genome is found
in a database called MITOMAP.
The main purpose of this database
is to report published and unpub-
lished data on variation of human
mtDNA, and variant tables cur-
rently (April 24, 2016) maintained
by the database report frequen-
cies from 30,589 human mtDNA
sequences (MITOMAP, 2016).
We used these variant tables as
the key reference for presenting
the rRNA and tRNA mutations
of mtDNA associated with mito-
chondrial disease. However, we
focused primarily on confirmed
associations between clinical phe-
notypes and mtDNA mutations,
using MITOMAP entry “Clinical
Phenotypes Associated with
mtDNA rRNA & tRNA Mutations,
Non-LHON” (which you can
access from http://www.mitomap.
org/foswiki/bin/view/MITOMAP/
ClinicalPhenotypesRNA#107).
When it comes to rRNA muta-
tions of mtDNA associated with
clinical phenotypes, only two cor-
relations are listed as confirmed in
BurchGene Magazine | December 2016
21
aforementioned entry, while there
is a significantly larger number of
tRNA mutations mentioned (Figure
3).
Great expectations – or not…?
The mutation rate of mtDNA is
extremely high and it is estimated
that it is 10- to 17-fold higher
than the mutation rate of nuclear
genome (Tuppen et al., 2010).
MtDNA repair systems, although
present, are not sufficient to coun-
teract the oxidative damage sus-
tained by the mtDNA because of its
proximity to the respiratory chain
complexes in the inner mitochon-
drial membrane and the reactive
oxygen species (ROS) they create.
Furthermore, no protective histones
are present whatsoever. Most alter-
ations of mtDNA are neutral poly-
morphisms, which have proved to
be a powerful mean of tracking
human migrations. The first patho-
genic mtDNA mutations were dis-
covered in 1988. Over 250 patho-
genic mtDNA mutations (point
mutations and rearrangements)
have been characterized since then
(Tuppen et al, 2010). These have
been shown to cause a wide variety
of diseases with a variable age of
onset and heterogeneity of pheno-
types. Disappointingly, we pres-
ently have no effective therapies
or cures available for patients with
mtDNA disease, although a few
exciting and promising experimen-
tal approaches for mtDNA disease
treatment are currently being inves-
tigated. It is still uncertain whether
they will make their way into the
clinic in the near future.
 22 P o p ular Topics in Genetic s
T H E 9 G R E AT E S T
GENETICISTS
    LIST OF THE TOP WELL-KNOWN           
1
Gregor Mendel (1822)
Gregor Mendel, also
knowns as the ‘the father of
genetics’ was born in Heizendorf,
Austria. This Austrian monk began
to research the transmission of
hereditary traits in plant hybrids in
his monastery’s garden. His love
of garden peas due to their many
distinct varieties, impacted cre-
ation of a seismic shift in biologi-
cal thinking when he came up with
the laws of inheritance. Mendel’s
experiments showed that the inher-
itance of certain traits in pea plants
follows particular patterns. This
observation became the foundation
of modern genetics and the study
of hereditary.
BurchGene Magazine | December 2016
Berina Alić & Halida Avdihodžić
                          
2 1 8Friedrich
65-
Transmitted
Miescher
H eredity
(1844)in Units
Swiss physician and biologist,
Johannes Friedrich Miescher was
the first researcher to isolate and
identify nucleic acid. Despite his
shyness and hearing handicap,
Miescher was an excellent student
who initially wanted to be a priest,
but his father opposed the idea and
Miescher entered medical school.
In 1869, while working under Ernst
Hoppe-Seyler at the University of
Tübingen, Miescher discovered a
substance containing both phos-
phorus and nitrogen in the nuclei
of white blood cells found in pus.
The substance, first named nuclein
became known as nucleic acid after
1874, when Miescher separated it
3
into protein and acid components.
This substance is now known as 1Oswald
9 11 - CAvery
h r o m (1877)
osomes
deoxyribonucleic acid (DNA). Carry Genes
Oswald Avery was born on October
21, 1877, in Halifax, Canada.
After graduating from Colgate
University, he accepted a research
position at the Rockefeller Institute
Hospital. In 1944, he and his
coworkers discovered that DNA
carries a cell’s genetic material
and can be altered through transfor-
mation. Although many scientists
acknowledge the impact of Avery’s
work on the field of molecular biol-
ogy, Oswald Avery did not win a
Nobel Prize. The reason might be
that Avery never publicly stated
that a gene is made of DNA. He
died on February 20, 1955.

4
1Erwin
9 5 2 - Chargaff
G e n e s (1905)
Are
Made of DNA
In 1944 Chargaff began his inves-
tigations into the composition of
DNA. By 1950 he had experimen-
tally determined and published cer-
tain crucial facts that led directly
to the correct elucidation of its
molecular structure. In particular,
he demonstrated three rules, now
known as Chargaff’s Rules, which
state organisms that in DNA the
ratio of the nucleic acid bases ade-
nine to thymine was roughly equal,
and that the ratio of cytosine to
guanine was also roughly equal.
His work laid the foundations for
Crick and Watson’s discoveries.
5
Rosalind Frenklin (1920)
British chemist Rosalind
Franklin earned a phD in phys-
ical chemistry from Cambridge
University. She is best known
for her role in the discovery of
the structure of DNA, and for her
pioneering use of X-ray diffrac-
tion techniques applied to DNA
fibers. ‘Dark lady of DNA’ made
some photographs that provided
key insights into DNA structure,
which helped Watson and Crick
to develop DNA model who took
credit for the discovery. Franklin
died of ovarian cancer at age 37.
Popular Topic s in Ge ne t ic s
6
Francis
1972- FirstCrick (1916)
recombinant &
DNA
James Watson (1928)
Francis Harry Compton
Crick was born on 8 June 1916
near Northampton. James Dewey
Watson was born on 6 April 1928
in Chicago and studied at the
universities of Chicago, Indiana
and Copenhagen. In 1951 in
Cambridge, Crick and Watson
started to work together. They
worked together on studying the
structure of DNA. In February 28,
they determined that the structure
of DNA was a double-helix poly-
mer, each containing a long chain
of monomer nucleotides, wound
around each other. This was one of
the most significant scientific dis-
coveries of the 20th century and
they won the 1962 Nobel Prize in
Medicine for discovery.
7 1Herbert
9 7 5Boyer
- D(1936)
N A
Herbert Wayne “Herb”
Boyer was born on 10 July 1936.
He is a researcher and entrepreneur
in biotechnology. He discovered
that genes from bacteria could be
combined with genes from eukary-
otes when he was a Professor of
Biochemistry at the University of
California, San Francisco. Also,
he discovered a method to coax
bacteria into producing foreign
proteins and by that started the
field of genetic engineering. He
received the 1990 National Medal
of Science.
BurchGene Magazine | December 2016
23
8
Alec Jeffreys (1950)
Professor Sir Alec John
Jeffreys was born on 9 January
1950 in Oxford, England. He is
a British geneticist, who devel-
oped techniques for DNA finger-
printing and DNA profiling. These
methods are used in forensic sci-
ence to assist police detective
work and to resolve paternity and
immigration disputes. After he fin-
ished his doctorate, he moved
to the University of Amsterdam,
where he worked on mammalian
genes as a research fellow. After
that he moved to the University of
Leicester in 1977, where in 1984
he discovered a method of show-
ing variations between individuals’
DNA, inventing and developing
genetic fingerprinting.
9
2James
0 0 3 - Thomson
C o m p l (1958)
etion
of the Human
James Alexander Thomson was
born on 20 December 1958. He is
an American developmental biol-
ogist best known for deriving the
first human embryonic stem cell
(SC) line in 1998. Also he is known
for deriving human induced plu-
ripotent stem (iPS) cells in 2007.
Thomson’s Lab in 1988, was the
first to report the successful iso-
lation of human embryonic stem
cells. Thomson’s group in 2007
reported a method for converting
human skin cells into cells that very
closely resemble human embryonic
 P o p ular Topics in Genetic s

BurchGene Magazine | December 2016

 Popular Topic s in Ge ne t ic s

BurchGene Magazine | December 2016

 P o p ular Topics in Genetic s

BurchGene Magazine | December 2016

 Popular Topic s in Ge ne t ic s

BurchGene Magazine | December 2016

GENES
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THE
GUN.
LIFESTYLE
PULLS
THE
TRIGGER.