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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 ?
Layla Abdel-Ilah
    COMPUTATIONAL BIOLOGY                                    
The DNA molecule in our Radiotekhnika journal, USSR. held the coded sequence—almost
cells carries genes which code and On August 16, 2012, research 55,000 strands in all. Each strand
produce all types of proteins and was published in the journal contained a portion of the text and
enzymes responsible for carrying Science by George Church and an address that identified the loca-
out all cell functions in addition to colleagues at Harvard University, tion in the flow of the book. In that
identify organism’s physical char- in which DNA was encoded with form, millions or even billions
acteristics. In addition, DNA mol- digital information that included copies of the book could fit easily
ecule has an important applications an HTML draft of a 53,400 into a test tube and, under normal
in forensic science, bioinformatics, word book written by the lead conditions, last for very long years.
molecular biology, etc. researcher, eleven JPG images and In January of 2013, researchers
Scientists know a lot about one JavaScript program. Multiple from the European Bioinformatics
DNA’s functions, and it is not a copies for redundancy were added Institute (EBI) reported an
surprise that they can implement and 5.5 petabits can be stored in improved system in Nature at the
its great benefits in different sci- each cubic millimetre of DNA. same time as Churce and colleagues
entific areas. However, the situa- This research result showed that (2013). The article was submit-
tion was different when we heard DNA can be another type of storage ted at around the same time as the
that DNA would be implemented medium such as hard drives and paper of Church and colleagues.
in data storage. magnetic tapes. Over five million bits of data con-
However, using DNA mole- Researchers started with digital sisting of text files and audio files
cules as a storage medium is not version of the book. Next, on paper, were successfully stored and then
a new idea in the scientific com- they translated the zeros into either perfectly retrieved and reproduced
munity. The general idea about the A or C of the DNA base pairs, with accuracy between 99.99%
the possibility of storing informa- and the ones into either the G or T. and 100%. The costs per mega-
tion on DNA molecules were orig- Then, using specific standard lab- byte were estimated at $12,400 to
inally made by Mikhail Neiman oratory techniques, they created encode data and $220 for retrieval.
and published in 1964–65 in the short strands of actual DNA that In May of 2016, PRI news

Figure 1: DNA can be used as a data storage medium

BurchGene Magazine | December 2016


Popular Topic s in Ge ne t ic s 5

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.

Figure 3: Storing a movie onto a DNA


published that Microsoft and team DNA strand contains a phos- example, 100101.
of researchers from University of phate group, a sugar group, and a Assume we want to store an
Washington have been preparing nitrogen base. There are four nitro- image in one DNA strand. The
DNA containing digital data for gen bases, namely (A)denine, (T) image is broken down into pixels.
sequencing, which allows them to hymine, (G)uanine and (C)ytosine. The brightness value of each pixel,
read and retrieve the original files. The sequence of base is a kind of available in form of binary number
The team was able to store 150 genetic code that is passed from is uniquely mapped to nitrogen
kilobytes on a strand of DNA. one generation to the next one. bases sequence, for example,
Oligonucleotides are short DNA 11010 is mapped to GATCAG.
The DNA molecule in our molecules, these small bits of Once the map is ready, DNA is
living cells is very small and dense nucleic acids can be synthesized in artificially synthesized in a labo-
which allow us storing all the data the laboratory as single strand mol- ratory. Once synthesized, DNA can
available in the world in 1 kg of ecule with any original sequence. be stored in test tubes for a long
DNA. DNA, especially if kept cool Storing data is an essential years, hundreds or even thousands.
and dry, has the ability to remain DNA function. In fact, much before When we wish to retrieve the data
intact for many years, and thereby the advent of semiconductors, DNA we just have to read the synthe-
enable the retrieval of molecules has been carrying genetic data for sized DNA using a DNA sequenc-
that are hundreds to thousands of generations, but the difference is ing techniques. This process will
years old. Moreover, our genetic in the format of data. DNA carries generate the exact sequence of base
material is very interesting for us data in form of sequence of nitro- pair, which can be turned back into
all the time so we will keep search- gen bases, for example, GTACCG, binary data and, in turn, the image
ing and discovering more and more whereas semiconductors carry can be regenerated.
about it. data in form of binary digits, for 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
Figure 2: Nitrogen bases sequence is available in form of binary photos, books, or videos: an exter-
number nal hard drive, or a strand of DNA.

BurchGene Magazine | December 2016


6 P o p ular Topics in Genetic s

LUIS AND REINHARD


REVEAL THEIR SECRETS
ABOUT DNA STORAGE
    INTERVIEW                                    
To better understand work of What methods are used in
scientist with DNA as a memory storing and reading of DNA?
storage, we spoke with Luis
Henrique Ceze, an University of “DNA synthesis is used
Washington associate professor of to make DNA molecules that
computer science and engineer- encode information (the “write”
ing and the university’s principal process). DNA sequencing is
researcher on the project. About used to read the composition
starting research on DNA he said: of the molecules that are then
„I’ve had a side interested in DNA decoded back to digital data.”
computing for a while, and while
on sabbatical in 2013 I head about Regarding the cost and
Nick Goldman’s work and got realistic expectation for com-
immediately interesting in explor- plete data storage in DNA
ing what a whole end-to-end would molecule, professor Ceze con-
look like. At that time my collab- cluded that it would have cost
orators Karin Strauss and Georg about $10 million to sequence
Seelig also got interested and we a human genome in 2007 but
put a research program together.“ close to only $1,000 in 2015, so
we can expect similar reduce in
We know that 0s and 1s as cost with the storage of data in
a binary code are used in data DNA due to technology devel-
storage, so how can we encode opment. In his opinion, it would
them in A, T, C and G? take around a decade for DNA
Figure 4: Luis Ceze, University of Washing- molecule to completely substi-
“First you need to break the ton associate professor of computer science tute classical devices used in data
information into units that would It is predicted that all digital storage.
fit in a molecule of about 100-200 data worldwide will grow to over
nucleotides. Then you map groups 16 zettabytes in 2017. Can DNA be Another scientist that spoke with
of 0s and 1s into ACGTs in a way possible solution to this problem? us about DNA storage is Reinhard
that avoids too many repeated Heckel, Dr. sc. techn., postdoc-
letters (like AAAA would be bad). Yes certainly, especially for toral researcher at the Department
This way, say a movie, would be archival storage that is not accessed of Electrical Engineering and
mapped to a large collection of very frequently. Computer Sciences, University
these molecules.” of California, Berkeley. He is a
What is current capacity of person that dealing with machine
What are main challenges in DNA molecule in storage, how learning, mathematical signal pro-
using DNA storage as a common much data can we store inside of it? cessing and above all computa-
tool in everyday life? tional biology. His interes in appli-
We estimate that we can fit cations in genomics and biology,
“DNA synthesis still needs to about 1 exabyte (~10^18) in about arises from believe that there are
get much cheaper and much faster 1 cubic inch. important problems in those areas
to be competitive.” and algorithmic and statistical

BurchGene Magazine | December 2016


Popular Topic s in Ge ne t ic s 7

longevity: Disks, flash, however other techniques exists


and tape in its current and can be used.
design cannot store There are several difficulties
information for more with reading the DNA, the main
than say a few decades. issue is that the reading process is
In contrast, DNA can not error free and additionally takes
serve an essentially time. However, a large number of
permanent storage reading errors are much less of a
medium, which makes problem in DNA data storage than
it attractive for archi- in biological and medical appli-
val applications.” cations, as we can account for
those with error correcting codes.
DNA can stay Another difficulty is that typically
stable in fossils for a not all sequences are read, but
long time and envi- again we can account for this by
ronmental condi- using error correcting codes.“
tions influences it
vastly. What can we You developed a scheme to
do to protect DNA correct errors in reading data based
from environmental on the Reed-Solomon Codes. Can
Figure 5: Reinhard Heckel, Dr. sc. techn., postdoctoral stresses? you explain how it works?
researcher at the Department of Electrical Engineer-
ing and Computer Sciences, University of California, “It is essential for “In a nutshell, error cor-
Berkeley DNA data storage to recting codes (such as Reed-
protect the DNA physi- Solomon Codes) add redundancy
ideas are crucial for addressing cally as well as information the- to the data, and therefore allow
those problems. oretically. My colleague Robert to correct errors, no matter where
Grass from ETH Zurich devel- the errors occur. To illustrate the
Why do you think that oped a technology for encapsulat- idea one can think about the sim-
the storage of data in DNA is ing DNA in Silica. This technol- plest code, which is a repetition
impressive? ogy allows to physically protect code. Specifically, if we want to
the DNA in a similar way than send a word, say ``DNA’’, we can
“DNA is considered an attrac- fossils do in nature. Additionally, simply transmit it several times,
tive future storage medium due to we protect the information theoret- e.g., send ``DNADNADNA’’. If
its longevity and high informa- ically by adding redundancy to the one error occurs, say we receive
tion density. More important for information that we want to store.” ``DNADNADNZ’’, we can still
storage than its density is perhaps decode the original informa-
its longevity: As our experimen- What is the current capacity of tion ``DNA’’ from the corrupted
tal results demonstrate, it is pos- a DNA molecule in storage, and message. However, a repetition
sible to recover information from how much data can we store inside code is not a good code as it adds
DNA even after thousands of of it? a lot of redundancy for the number
years. Therefore, DNA has poten- of errors that it can correct. Coding
tial applications in future long term “A loose lower bound on the theory is about finding an optimal
storage.” capacity is two bits per nucleotide. tradeoff between the number of
However, this capacity cannot be errors that can be corrected and
Can we use some other mole- achieved as errors on the nucle- the redundancy that is added.
cules beside DNA as a data storage otide level occur and one has to Moreover, coding theory addresses
system? account for those. Additionally, the computationally efficient recon-
entire fragments of DNA do get struction of the information.
“In principle, yes. One of the lost. The capacity we achieved was In DNA data storage, the
reasons that DNA is a natural 1.187 bits per nucleotide.” information is stored on several,
choice is that there are already non-connnected, strands of DNA.
technologies available that can The story does not end once the Errors occur in individual
write and read DNA.” data is inside of the DNA. How do sequences, and additionally whole
you read this data? Are there any sequences get lost.
What is the advantage of DNA difficulties with it? We developed a code that is
data storage over standard data capable of correcting errors in
storage devices? “There are several technologies single nucleotides, and additionally
for reading (sequencing) DNA, allows to recover entire sequences
“The main advantage over con- we used an Illumina sequencer, that are lost.”
ventional data storage devices is its

BurchGene Magazine | December 2016


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 9

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

BurchGene Magazine | December 2016


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

DNA
I N F O G A L L E RY
BurchGene Club
    DNA UNDERSTANDING                                     

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

G
more dispersed form called chro-
enome is the complete matin. The number of chromo-
genetic or DNA comple- somes is characteristic for the spe-

E
ment of an organism. It includes cies concerned. In a bacterium only
the genetic material of the nucleus one chromosome is evident as the ach duplicated chromosome
and cytoplasm. All organisms have cell is about to divide. After DNA has two sister chromatids,
a genome made up of DNA, con- replication, the two new chromo- which are joined coppies of the
taining genes. Genomes may vary somes attach to a specialized site original chromosome. The two
in their size, number of genes, on the bacterial plasma membrane chromatids, each containing an
number of chromosomes, and how for segregation to the two daugh- identical DNA molecule, are ini-
genes are organized within chro- ter cells. tially attached all along their leng-
mosome(s), and the DNA may be hts by protein complexes called
circular or linear. A given organ- cohesins; this attachment is known
ism has only one genome regard- as sister chromatid cohesion. Each
less of whether the organism is sister chromatid has a centromere,
haploid, diploid, or polyploid. The a region of the chromosomal DNA
term was originally used to denote where the chromatid is attached
one haploid set of chromosomes in most closely to its sister chroma-
a eukaryote organism. The genome tid. This attachment is mediated
projects are having a profound by proteins bound to the centro-
impact on health-care discoveries. meric DNA; other bound proteins
The main purpose of genome proj- condense the DNA, giving the
ects is to access the entire genome duplicated chromosome a narrow
sequences that can be used to find „waist“. The portion of a chromatid
out the probable genes and their to either side of the centromere is
functions in various organisms. referred to as an arm of the chro-
Some important genomes that are matid. Later in a cell division pro-
partially or completely sequenced cess, the two sister chromatids of
include that of e.coli,, yeast, arabi- each duplicated chromosome sepa-
dopsis, drosophila, mice, humans, rate and move into the new nuclei,
rice,etc. one forming at each end of a cell.

BurchGene Magazine | December 2016


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-

D N
ated histone; about 146 base pairs
NA-looping mechanisms of the DNA comprise a core par- ucleotide is one of the struc-
are part of networks that ticle and the remainder form the tural components, or build-
regulate all aspects of DNA metab- linker DNA. ing blocks, of DNA and RNA. A
olism, including transcription, rep- nucleotide consists of a base (one
lication, and recombination. DNA of four chemicals: adenine, thy-
loop formation may have different mine, guanine, and cytosine) plus a
functions in different cellular con- molecule of sugar and one of phos-
texts; in some cases, the loop itself phoric acid.C, T, and U are called
is requisite for regulation, while in pyrimidines and each has a single
others the increase in the effec- nitrogen-containing ring. A and G
tive local concentration of pro- are called purines and each has two
tein may account for the effects nitrogen-containing rings.
observed. The ability of DNA to
form loops is affected by the dis-

D
tance between binding sites; by the
DNA sequence, which determines NA or deoxyribonucleic
deformability and bendability; and acid is an very important
by the presence of other proteins molecule found in every living
that exert an influence on the con- organism. It’s responsible for
formation of a particular sequence. 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

D
the DNA double helix . Each base
is the basic physical and functional
NA eukaryotic cells is unit of heredity. forms hydrogen bonds to a base
packed by association with in the other strand. There are two
specific proteins such as the his- types of bases in DNA: purines
tones into a structure known as (guanine and adenine) and pyrim-
chromatin. The fundamental unit idines (cytosine and thymine).
of this structure is the nucleosome Each base pair consists of one
in which the DNA is wrapped twice purine connected to a pyrimidine
around a unit of eight histone mol- via hydrogen bonds. Guanine pairs
ecules. This structure is compacted only with cytosine (G-C) via three
further into the so-called solenoid hydrogen bonds. Adenine pairs
structure in genes that are not tran- only with thymine (A-T) in DNA
scriptionally active or about to or uracil (A-U) in RNA. Because
become active. The tightly packed an adenine-thymine (A-T) or ade-
solenoid structure can be com- nine-uracil (A-U) base pair is held
pacted even further, by extensive together with only two hydrogen
looping, to form the chromosomes bonds, it requires less energy to
that are visible during cell division. 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 (Figure-2) are tumors associated respectively. Inactivation of SDHD
subunit of succinate dehydroge- with nervous system and muta- gene in patient with paraganglioma
nase. Scientists have recognized tions found on genes have effect is associated with the complete and
four types of inherited paragangli- on catalytic subunits of complex selective loss of complex II elec-
oma-pheochromocytoma, named II (flavoprotein and iron protein), tron transfer activity and with loss
types 1 through 4. Every type is SDH enzyme activity and mito- of the succinate dehydrogenase
recognized by its genetic cause. chondrial morphology. (mediated step of the Krebs cycle).
Individuals with types 1, 2, and 3 Mitochondrial diseases are
commonly create paragangliomas extremely difficult to diagnose due
in the head or neck area. Hereditary to extreme locus and allelic hetero-
paraganglioma-pheochromocy- geneity, with both nuclear and mito-
toma is commonly diagnosed in a chondrial genes potentially respon-
man’s 30s. Symptoms of heredi- sible. There are different types of
tary paraganglioma are elevations mutations such as insertion, dele-
in blood pressure, headache, epi- tion, substitution, transition that
sodic profuse sweating, irregular can lead to change of amino acid
heartbeat, pallor, and apprehen- and result in truncated protein or
sion or anxiety. Paragangliomas complete loss of protein function.
are vascularized tumors that can Figure 2: representation of paragan- So far, a number of mitochondrial
be benign, malignant, functional glioma formed on the neck syndromes correlated with muta-
or nonfunctional. The areas in tions in nuclear genes are identi-
which paraganglioma can be SDHC and SDHD encode for fied. Significant clinical variabil-
found is in the neck, head, pelvic integral membrane-protein sub- ity in individuals that do not fit per-
areas, thoracic and abdominal area. units. Mutations in all these genes fectly into one particular syndrome
Pheochromocytomas are catechol- result in neoplasia which is the further complicates the diagnosis.
amine-secreting paragangliomas formation or presence of a new, More research with focus on iden-
found in the adrenal part and they abnormal growth of tissue. SDHD tification of nDNA and ntDNA
are also known as adrenal chro- is gene that encode for small mutations that are associated with
maffin tumors. Clinical features subunit of cytochrome b in suc- particular mitochondrial disorder
of catecholamine excess include ciate-ubiquinone oxidoreductase and development of specific diag-
hypertension, headache, sweat- (complex II) while SDHC code nostic assays are required. The era
ing, palpitation. Burnichon et al, for large subunit of cytochrome b of massively parallel sequencing
(2009) reports that in the 2000. and in succinate-ubiquinone oxidore- promises a faster pace of discov-
2001., genes that encode for three ductase and they are connected to ering genes involved in mitochon-
subunits of the succinate dehydro- type 1 and type 2 paraganglioma drial biogenesis.
genase enzyme (SDHD, SDHB Table 2: Mutation found in sturctual and non-structural nuclear
and SDHC genes) have major genes correlated with autosomal dominant paraganglioma
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
BurchGene Magazine | December 2016
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

Jasin Hodžić
    HUMAN GENETICS                                    
Interest in mitochondria and but a crafty trickster. a cell is not an excludable situa-
their genome has blossomed over tion, and such case is defined as
the last few decades. As the gath- Mitochondrial DNA – a loop heteroplasmy.
ered knowledge expanded, the dis- with a twist Human mtDNA is strictly
eases caused by mitochondrial dys- inherited uniparentally, through
functions have become an important In evolutionary sense, mito- the maternal lineage, and contains
area of human pathology. Human chondria are generally consid- only 37 genes. These genes encode
mitochondrial DNA (mtDNA) is ered to be remains of ancient bac- 13 polypeptides which are all core
a small gene-rich, circular mole- terial symbionts, and as such they subunits of respiratory chain com-
cule of 16,569 bp. Besides the 13 are thought to have transferred the plexes I, III, IV, and V, as well as
components of oxidative phosphor- majority of their genome to the host the RNA necessary for mtDNA
ylation, mtDNA encodes 2 ribo- cell over time, facilitating creation translation: 2 rRNAs (12S and 16S)
somal RNAs and 22 tRNAs. Those of all contemporarily known nucle- and 22 tRNAs. Schematic over-
rRNAs and tRNAs are necessary ated eukaryotic cells (Margulis, view of the structure of mtDNA
for the synthesis of 13 polypeptides 1971). All that has remained is a is shown on the Figure 1 below.
in mitochondria and therefore crit- compact, app. 16,569 bp long, dou- Human mtDNA genes contain no
ical for oxidative phosphorylation ble-stranded, circular DNA whose introns and almost no intergenic
process. In this article we will take complete sequence was fully elu- noncoding nucleotides, except the
a look at rRNA and tRNA muta- cidated in 1981 and further revised 1.1 kb displacement loop (D-loop),
tions of mtDNA associated with in 1999 (Tuppen et al., 2010). In which contains transcriptional pro-
mitochondrial disease so far, and a single eukaryotic cell, several moters, as well as at least one of the
we will try to provide a compre- hundreds or thousands of copies proposed replication origins (OH)
hensive overview of the research of the mitochondrial genome are (Figure 1).
and materials published on this present at any given time. A sit-
topic, and discuss the future direc- uation known as homoplasmy Specific features of mtDNA
tion of the research in this area. We prevails if all mtDNA molecules diseases
will begin with outlining the pecu- present within a cell are identical.
liarities of mitochondrial genetics However, the presence of two or There is a number of features
and mtDNA – a humble molecule, more mitochondrial genomes in which govern the clinical symp-
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
Figure 1: Human mitochondrial DNA map by the ratio of wild-type to mutant

BurchGene Magazine | December 2016


Popular Topic s in Ge ne t ic s 21
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 Figure 3: Genotype to phenotype correlations in
occur, as discussed in the previous certain human mitochondrial diseases
section, and shown in Figure 2.
(3) Clonal expansion: Clonal clinical syndromes associated with aforementioned entry, while there
expansion is defined as the pref- mtDNA mutations is their extreme is a significantly larger number of
erential amplification of mtDNA variability. Furthermore, they can tRNA mutations mentioned (Figure
mutations to a high level in manifest at any stage in life of 3).
post-mitotic tissues. Such expan- patients. The age of onset reflects Great expectations – or not…?
sion is considered to be a result of the level of mutation and the sever-
random genetic drift, dependent ity of the biochemical defect on The mutation rate of mtDNA is
on relaxed replication of the mito- the whole. However, other factors extremely high and it is estimated
chondrial genome (Elson et al., (such as nuclear genetic and envi- that it is 10- to 17-fold higher
2001), as can be seen on Figure 2. ronmental factors) also have an than the mutation rate of nuclear
(4) Genetic bottleneck of effect on the expression of disease genome (Tuppen et al., 2010).
mtDNA: Heteroplasmic mtDNA (Tuppen et al., 2010). MtDNA repair systems, although
genotypes in mammals rapidly seg- present, are not sufficient to coun-
regate between generations. This Current compendium of poly- teract the oxidative damage sus-
phenomenon, along with a return morphisms and mutations in human tained by the mtDNA because of its
to homoplasmy in some progeny, mitochondrial genome is found proximity to the respiratory chain
strongly suggests the existence in a database called MITOMAP. complexes in the inner mitochon-
of an mtDNA bottleneck during The main purpose of this database drial membrane and the reactive
development (Tuppen et al., 2010). is to report published and unpub- oxygen species (ROS) they create.
The exact mechanism by which this lished data on variation of human Furthermore, no protective histones
genetic bottleneck occurs is cur- mtDNA, and variant tables cur- are present whatsoever. Most alter-
rently subject of fierce debates. A rently (April 24, 2016) maintained ations of mtDNA are neutral poly-
prevalent hypothesis states that this by the database report frequen- morphisms, which have proved to
bottleneck arises during embryonic cies from 30,589 human mtDNA be a powerful mean of tracking
development, and that it is driven sequences (MITOMAP, 2016). human migrations. The first patho-
by a marked reduction in mtDNA We used these variant tables as genic mtDNA mutations were dis-
copy number in the germ line (Cree the key reference for presenting covered in 1988. Over 250 patho-
et al., 2008). the rRNA and tRNA mutations genic mtDNA mutations (point
One of the key features of of mtDNA associated with mito- mutations and rearrangements)
chondrial disease. However, we have been characterized since then
focused primarily on confirmed (Tuppen et al, 2010). These have
associations between clinical phe- been shown to cause a wide variety
notypes and mtDNA mutations, of diseases with a variable age of
using MITOMAP entry “Clinical onset and heterogeneity of pheno-
Phenotypes Associated with types. Disappointingly, we pres-
mtDNA rRNA & tRNA Mutations, ently have no effective therapies
Non-LHON” (which you can or cures available for patients with
access from http://www.mitomap. mtDNA disease, although a few
org/foswiki/bin/view/MITOMAP/ exciting and promising experimen-
ClinicalPhenotypesRNA#107). tal approaches for mtDNA disease
When it comes to rRNA muta- treatment are currently being inves-
Figure 2: Schematic overview of mitochon- tions of mtDNA associated with tigated. It is still uncertain whether
drial mitotic (vegetative) segregation and clinical phenotypes, only two cor- they will make their way into the
relaxed replication phenomena. relations are listed as confirmed in clinic in the near future.

BurchGene Magazine | December 2016


22 P o p ular Topics in Genetic s

T H E 9 G R E AT E S T
GENETICISTS
Berina Alić & Halida Avdihodžić
    LIST OF THE TOP WELL-KNOWN                                     

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

1
1874, when Miescher separated it

3
Gregor Mendel (1822) into protein and acid components.
This substance is now known as 1Oswald
9 11 - CAvery
h r o m (1877)
osomes
Gregor Mendel, also deoxyribonucleic acid (DNA). Carry Genes
knowns as the ‘the father of
genetics’ was born in Heizendorf, Oswald Avery was born on October
Austria. This Austrian monk began 21, 1877, in Halifax, Canada.
to research the transmission of After graduating from Colgate
hereditary traits in plant hybrids in University, he accepted a research
his monastery’s garden. His love position at the Rockefeller Institute
of garden peas due to their many Hospital. In 1944, he and his
distinct varieties, impacted cre- coworkers discovered that DNA
ation of a seismic shift in biologi- carries a cell’s genetic material
cal thinking when he came up with and can be altered through transfor-
the laws of inheritance. Mendel’s mation. Although many scientists
experiments showed that the inher- acknowledge the impact of Avery’s
itance of certain traits in pea plants work on the field of molecular biol-
follows particular patterns. This ogy, Oswald Avery did not win a
observation became the foundation Nobel Prize. The reason might be
of modern genetics and the study that Avery never publicly stated
of hereditary. that a gene is made of DNA. He
died on February 20, 1955.
BurchGene Magazine | December 2016
Popular Topic s in Ge ne t ic s 23

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

8
and Copenhagen. In 1951 in
Cambridge, Crick and Watson Alec Jeffreys (1950)

4
started to work together. They
1Erwin
9 5 2 - Chargaff
G e n e s (1905)
Are worked together on studying the Professor Sir Alec John
Made of DNA structure of DNA. In February 28, Jeffreys was born on 9 January
they determined that the structure 1950 in Oxford, England. He is
In 1944 Chargaff began his inves- of DNA was a double-helix poly- a British geneticist, who devel-
tigations into the composition of mer, each containing a long chain oped techniques for DNA finger-
DNA. By 1950 he had experimen- of monomer nucleotides, wound printing and DNA profiling. These
tally determined and published cer- around each other. This was one of methods are used in forensic sci-
tain crucial facts that led directly the most significant scientific dis- ence to assist police detective
to the correct elucidation of its coveries of the 20th century and work and to resolve paternity and
molecular structure. In particular, they won the 1962 Nobel Prize in immigration disputes. After he fin-
he demonstrated three rules, now Medicine for discovery. ished his doctorate, he moved
known as Chargaff’s Rules, which to the University of Amsterdam,
state organisms that in DNA the where he worked on mammalian
ratio of the nucleic acid bases ade- genes as a research fellow. After
nine to thymine was roughly equal, that he moved to the University of
and that the ratio of cytosine to Leicester in 1977, where in 1984
guanine was also roughly equal. he discovered a method of show-
His work laid the foundations for ing variations between individuals’
Crick and Watson’s discoveries. DNA, inventing and developing
genetic fingerprinting.

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-

9
otes when he was a Professor of

5
Biochemistry at the University of 2James
0 0 3 - Thomson
C o m p l (1958)
etion
Rosalind Frenklin (1920) California, San Francisco. Also, of the Human
he discovered a method to coax
British chemist Rosalind bacteria into producing foreign James Alexander Thomson was
Franklin earned a phD in phys- proteins and by that started the born on 20 December 1958. He is
ical chemistry from Cambridge field of genetic engineering. He an American developmental biol-
University. She is best known received the 1990 National Medal ogist best known for deriving the
for her role in the discovery of of Science. first human embryonic stem cell
the structure of DNA, and for her (SC) line in 1998. Also he is known
pioneering use of X-ray diffrac- for deriving human induced plu-
tion techniques applied to DNA ripotent stem (iPS) cells in 2007.
fibers. ‘Dark lady of DNA’ made Thomson’s Lab in 1988, was the
some photographs that provided first to report the successful iso-
key insights into DNA structure, lation of human embryonic stem
which helped Watson and Crick cells. Thomson’s group in 2007
to develop DNA model who took reported a method for converting
credit for the discovery. Franklin human skin cells into cells that very
died of ovarian cancer at age 37. closely resemble human embryonic

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


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


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