urch ene BSemestral magazine of Genetics andG Bioengineering Department ISSUE 01/MAY 2016

FORENSIC GENETICS ALZHEIMER’S DISEASE NEUROSCIENCE GENE THERAPY

Genetics for CSI Question??? A Love Story Disease treatment? Great introduction in forensic Is Alzheimer’s in your genes? Scientist from Harvard about Problems and Prospects of genetics on crime scene p.8 p.20 neuroscience and genetics p.16 Gene Therapy p.18 LEARN NEW THINGS ABOUT HISTORY OF GENETICS 2 History of Genetics

Genetics is more than a “laboratory science”; unlike some other areas of science, because genetics has a direct impact on soci- ety. So what is genetics? We heard a lot of times that genetics is the scien- tific study of heredity, but like all defi- nitions, this leaves a lot unsaid. To be more specific, what geneticists do is study how traits (such as eye color and hair color) and diseases (such as cys- tic fibrosis and sickle cell anemia) are »» p.8 passed from generation to generation . »» p.18

BurchGene magazine Broaden your horizons Dear colleagues, students, respected professors, collabora- Executive editors: tors and respected readers. It is a great pleasure and honour to Ahmed Osmanović present to you the first ever student magazine „Burch Gene“, Adnan Fojnica here at our department for Genetics and Bioengineering.

Editorial board: Finally, “Burch Gene” magazine saw the daylight. Our goal Prof. Dr. Damir Marjanović was to introduce students, professors and the public to the basic Prof. Dr. Mirsada Hukić ideas behind genetics and bioengineering. Introduce them with Assist. Prof. Dr. Almir Badnjević definitions, concepts, applications and benefits these branches Assist. Prof. Dr. Serkan Dogan of science provide to human kind. Also, to better understand Assoc. Prof. Dr. Enisa Omanović science in general and to demystify some common myths we can hear about, read in newspapers, watch on TV and similar. Text authors: Prof. Dr. Rifat Hadžiselimović In this very first edition, we will introduce you with his- Prof. Dr. Damir Marjanović torical aspects and application of Mendelian and molec- Assoc. Prof. Dr. Enisa Omanović ular genetics, biomedical engineering, forensics, nano- Assist. Prof. Dr. Almir Badnjević technology, bioinformatics, neuroscience and many other MS Elma Ferić-Bojić interesting topics. You will be able to read some interest- Lejla Gurbeta ing facts about genetics and to introduce yourselves with Adna Ašić common genetics’ diseases and ways they can be treated. Larisa Bešić Adnan Fojnica All the topics are written with simple style, affordable and Dijana Sejdinović understandable for readers that are not so familiar with genet- Anis Čilić ics from one side, in same time very comprehensive and edu- Džana Mulaomerović cational for people that are dealing with genetics, bioengi- Ahmed Osmanović neering and science in their everyday lives, from another side.

Lector: For realization of this project, we spent a lot of time Sabina Halilović and gave a lot of effort, but without a doubt, our edito- rial board and collaborators have given their maximum in Graphical Design: order to achieve desired goal. Magazine is of course free, Ahmed Osmanović we are stick to belief that knowledge is right not privilege.

Publisher: Using this opportunity we would like to thanks to everyone International Burch University who have recognized our work and vision, also contributed for publication of this very first number of „Burch Gene” magazine. Address: Francuske revolucije bb, Ilidža 71210 At the end, special thanks to our sponsors: International Burch University and Verlab. Telephone: 033 782-130 We hope you delight in reading these pieces E-mail: [email protected] The Editors

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CONTENTS

4 MILESTONES OF GENETICS

The widespread thinking is that Gregor Mendel set basis for modern genetics. However it was preceded by numerous, smaller or larger contributions to this science. 8 GENETICS ON CRIME SCENE

Forensic genetics is one of the rare scientific disciplines in which antiheroes had a significant impact in raising public awareness about the necessity of DNA analysis. 11 BIOMEDICAL ENGINEERING

In 2000, German archeologists uncovered a 3,000-year old mummy from Thebes »» p.12 »» p.16 with a wooden prosthetic tied to its foot to serve as a big toe. 14 SCIENCE ABOUT SMALL

The ideas and concepts behind nanoscience and nanotechnology started with a talk entitled “There’s Plenty of Room at the Bottom” by physicist Richard Feynman. 16 A LOVE STORY Your brain is built of cells called neurons and glia – hundreds of billions of them. And each of them contains the entire human genome. 18 FROM GENES TO THERAPY

»» p.19 If genes don’t work properly, they can cause disease. Gene therapy seems like ideal »» p.11p.4 »» p.14 solution for treating a wide range of diseases, including cancer, diabetes and AIDS. 20 IS ALZHEIMER´S IN YOUR GENES?

Alzheimer´s disease is a degenerative disease of brain that results in dementia or loss of memory, and ability to function. 2 in 3 people with AD are women. 22 A, C, G & T

A, C, G & T are ‘’letters’’ that write ‘’book of life’’ inside each of us. It took too long for humans to decipher these ‘’letters’’. A TRIP DOWN MEMORY LANE »» p.7 24 When we are talking about molecular genetics we can surely say ideas that are currently unimaginable are soon going to become history. 26 9 GREATEST DISCOVERIES

Here’s a look at some discoveries that have changed the world of genetics. It’s impossible to rank their importance, so they’re listed in the order they were discovered. »» p.22

BurchGene Magazine | May 2016 4 History of Genetics MILESTONES OF GENETICS Rifat Hadžiselimović DISCOVERIES AND EVENTS

From the origins of human cognition patterns on our planet, members of the human race tend to evolve to surpass their predecessors. According to the earliest written ev- idence, Homo sapiens tend to use the genetical potential of the interesting species, by using core genetics forms, from which some were not explained untill the distant future and modern epoch. It is widely known that Gregor Mendel (1822-1884) set the basis (1869.) for all fields of modern genetic research. In the early 20th century, the science that he was involved with is referred to as Mendelism, with the qualification “science of inheritance” ... However, as in all other areas of hu- man knowledge, it was preceded by numerous, smaller or larger contributions to this science, which originate from the deepest layers of civilization. Such areas have long been works of ingenious in- dividuals amateurs who were not considered scientists, and nor did they fully grasp the science.

1. Early theories and interacted in the womb to direct an Hebrew - Judah ibn Tibbon. applications organism’s early development. For In 1000 CE, the Arab physi- both Hippocrates and Aristotle— cian, Abu al-Qasim al-Zahrawi 3000. CE - Targeted cross and nearly all Western scholars (known as Albucasis in the West) breeding between domestic through to the late 19th century— was the first physician to describe animals. the inheritance of acquired charac- clearly the hereditary nature of hae- The Egyptians, Greeks and teristics was a supposedly well-es- mophilia in his Al-Tasrif. Romans crossed horses with the tablished fact that any adequate VI century CE, - Heraclitus is aim of “processing”. theory of heredity had to explain. the founder of the dialectical-ma- Assyrians and Babylonians dis- At the same time, individual species terialist view of the world: ‘’ Panta tinguished male and female tree were taken to have a fixed essence; Rei ‘(everything moves). Matter, dates, and the number of males such that inherited changes were including wildlife, everywhere, is were minimized in order to achieve merely superficial. constantly changing. It is a single higher yields. In the 9th century CE, the Afro- concept - only manifests itself The most influential early Arab writer Al-Jahiz considered the in various forms. There exists a theories of heredity were that effects of the environment on the present struggle of opposites: of of Hippocrates and Aristotle. likelihood of an animal to survive. living occurs life, but life can not Hippocrates’ theory (possibly based In 1140 CE, Judah HaLevi exist without death; the origin does on the teachings of Anaxagoras) described dominant and recessive not go without fail; light without was similar to Darwin’s later ideas genetic traits in The Kuzari. “This darkness; beginning with no end. on pangenesis, involving hered- phenomenon is well known in V Century CE - Empedocles ity material that is collected from inheritance, because very often we suggested the four elements: water, throughout the body. Aristotle sug- have a son who does not look like earth, air and fire - and culminates gested instead that the (nonphys- his father, and instead looks like ancient materialism. His philos- ical) form-giving principle of an his grandfather. Without a doubt, ophy is the forerunner of the sci- organism was transmitted through inheritance and likeness were entific process. Interestingly, semen (which he considered to be found within his father, though they Empedocles hypothesis sugests a purified form of blood), and the were not visible from the outside.” that living organisms are formed by mother’s menstrual blood, which assembling individual anatomical

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1694th - Rudolph Camerarius, German professor of medicine, described sexual reproduction in plants. As far as is known, this was the first recorded production of artificial hybrids, which prompted an experimental approach to hybridization. 1717th - Thomas Fairchild, English explorer announced results of successful pollination between related plants. Hybrids displayed Figure 1 Albucasis and two pages from his original crowning achievement, his traits of both parents, which are magnum opus, was a 30 volume encyclopedia of medicine and surgery called Kitab known as Fairchild’s sweet William al-Tasrif or Fairchaild’s mule. parts that are independently formed soul which enters into the fetus. 1735-38. - Swede Carl in nature. After that, these parts are Each of these four factors had Linnaeus (published under the held in a harmonious whole form, four parts creating sixteen factors Latin name Carolus Linnaeus) which indicates the modern views of which the karma of the parents made the first taxonomic sys- on the selection and genetic struc- and the soul determined which attri- tematization of living beings (in ture of populations. butes predominated and thereby epochal work Systema Naturae, IV century CE - Aristotle gave the child its characteristics. in the Netherlands), whose basis contributed immensly to ancient and criteria are not significantly science. He visualized the immense 2. Transitional epoch changed untill now. Line described biological diversity, ie, the fact that the sexual organs of many plants living beings are heterogeneous Since ancient times, the first and experimentally produced their and that they are graded complexes ideas on the development of living hybrids. in a conspicuous development line. nature and biological inheritance to In 1760. - Joseph Kölreuter is The entire material world is clas- the great discoveries in the field of the founder of quantitative genet- sified as a hierarchical set of com- natural sciences in the 16th century ics and practical hybridization. By plexity: from minerals through has been recorded (for biology). experimenting with high and dwarf plants and animals to man. During this long period, the Roman varieties of tobacco, he noted that III century CE - In Europe, Empire, Aristotle and other figures hybrids of the first generation are about 10 centuries of absence spilled over works that were “sea- intermediate, and that in another traced the development of science soned” interpretations of transla- they have “normal distribution”, ie. in general and even biology. tors (these interpretations where they are often more exuberant than In the Charaka Samhita of mostly stolen or had serious omis- parents and that there is no differ- 300CE, ancient Indian medical sion). It so happened that the origi- ence in reciprocal crosses. writers related the characteristics nal ancient ideas in Western Europe George Leclerc Buffon was of a child as four factors: drew only on the threshold of the a French naturalist -evolution- (1) those from the mother’s 13th century, thanks to the expan- ist, who insisted on the empirical reproductive material, sion of Arab culture, that it is much belief that living species are chang- (2) those from the father’s earlier assumed. Among the many ing and that the biological diversity sperm, minds of the time, in different is a product of time. (3) those from the diet of the fields of natural sciences, in med- Erasmus Darwin, grandfather pregnant mother and icine certain figures particularly of Charles Darwin also recorded (4) those accompanying the stood out: Al-Kindi, Al Rhases, Al similar conclusions and, as Buffon, Gaber, Abu Ibn Sina (Avicenna). In thought that acquired characteris- Europe is rooted the original sci- tics are transmitted to the offspring. entific ideas, in which Copernicus, Galileo, Newton, Descartes and 3. XVIII and XIX other scholars had most of the century credit. In terms of biology, Vesalius, Harvey and Leeuwenhoek domi- In the 18th century, with nated. Due to the accumulation of increased knowledge of plant and recorded biological data, there is a animal diversity and the accom- need for their systematization and panying increased focus on tax- organization. onomy, new ideas about hered- 1682nd - Nehemiah Crew, ity began to appear. Linnaeus English plant anatomist, under and others (among them Joseph Figure 2 Empedocles’s four world: went the first consistent study of Gottlieb Kölreuter, Carl Friedrich water, earth, air and fire plant reproductive organs. von Gärtner, and Charles Naudin)

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conducted extensive experi- biologist discovers colored bodies, medicine. ments with hybridization, espe- chromosomes, and named them cially hybrids within species. after the Greek prefix chroma (= 4. Classical genetics Species hybridizers described a color) + soma (= body), because wide variety of inheritance phe- they are visible as stains when cells 1902 - US and German cytol- nomena, include hybrid steril- received specific colors. ogists independently observed the ity and the high variability of 1893. – Friedrich Leopold links between Mendel’s “units back-crosses. August Weismann - German Jew, of heredity” and chromosomes. In 1809. - Jean-Baptiste a biologist, has developed one They conclude that hereditary Lamarck, a French biologist, of the first theories of biological information is contained in the creator of the first complete theory inheritance. Although some his chromosomes. of evolution, at the beginning of views were later rejected, unques- 1902 - William Bateson intro- the 18th century, has also attributed tionably was the originator of the duces the name gene for Mendel’s great importance to biodiversity. modern theory of organic inher- “inheritance factor”. He discovered a theory of inheri- itance and evolutionary route 1905 - Wilhelm Ludwig tance of acquired characteristics in known as neo-Darwinism (‘’Über Johannsen, a Danish botanist intro- the book ‘Zoological Philosophy’. die Vererbung’’). He assumed duces the concepts: genotype and 1835th - Hugo von Mohl, a that in every cell in early embry- phenotype in the work „Om arve- German botanist discovers mitosis onic development, differentiated lighed i samfund og i rene linier“ in plants. German zoologist Otto somatoplazma (“catfish”) and and the book „Arvelighedslærens Bütschl was one of the first germ-plasma (“” germ “) existed. Elementer“, which was expanded researchers who may have found According to him, the germplasm and translated into German under the discovery process today known is a basic unit of heredity, and is not the title „Elemente der exakten as mitosis, and the term is defined affected by environmental factors. Erblichkeitslehre“. by Walther Flemming (1882). Reproduction of animals, not com- 1905 - William Bateson, a In the early years of the 19th plicate somatic cells but germ- British biologist and evolutionist century Augustin Sager established plasma, which are “unchanged”, created the term genetics. relationship of dominance, noticing are transmitted in a series of gen- 1909 - Wilhelm Ludwig that such properties, if it has at least erations. The effect of running in Johannsen, a Danish botanist, one parent, regularly occur in the one direction: calling (germ) cells according to some, proposes the offspring. He also found that some produce somatic cells from somatic term gene, according to genotype parental features do not appear in cells “learn” the appropriate capac- and genetics. The sex chromo- any of the offspring. This system ity of the body. Hereditary infor- somes were found in the works of is also confirmed by the farmers mation can not pass some of the the butterflies and other insects. of agricultural plants in England. germ and the next generation. He 1859 - Charles Darwin pub- established the “theory of germ 1910. – 1920. lished “Origin of Species by plasma. Means of Natural Selection ‘’ (‘’ 1900 - Rediscovery of 1910th - Thomas Hunt Morgan The Origin of Species by means Mendel’s work and affirmation first discovered sex-linked prop- of natural selection or preservation of the meaning of its results (Carl erties while studying the fruit fly of favored races in the struggle for Correns, Erich von Tschermak and Drosophila. He discovered that the life ‘’). Hugo de Vries) marked the begin- gene for eye color is on the X chro- 1865 - Gregor Mendel pub- ning of rapid development and dif- mosome, and it is also the first loca- lished ‘’ The research on plant ferentiation of genetic research, tion of a gene on a particular chro- hybrids ‘’ (‘’ Versuch über Pflanzen- which characterize the modern era mosome. Morgan reveals crossing HYBRID ‘’). of development and even biolog- over, ie, recombination of paren- 1876 - Oscar Hertwig discov- ical sciences, biotechnology and tal chromosomes during meiosis. ered meiosis. She described this phenomena again in 1883, at the level of chromosomes (Belgian zoologist Edouard Van Beneden, in eggs of Ascaris worms of the genus). The significance of meiosis for reproduction and inher- itance, however, described only in 1890. German biologist August Weismann, who noted that two cell division necessary to transform one diploid cell into four haploid cells if the number of chromosomes should be maintained. Figure 3 Thomas Hunt Morgan was first discovered sex-linked (sex-linked) proper- 1882 Walter Fleming - German ties, while studying the fruit fly Drosophila.

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Researchers Thomas Hunt Morgan, and not only DNA. Alfred Sturtevant, Calvin Bridges 1970: Restriction enzymes and the other on vstama Drosophila were discovered in studies of bac- genetics explain sex and sex-linked terium, Haemophilus influenzae, inheritance. Thomas Hunt Morgan enabling scientists to cut and paste suggested that genes are contained DNA in the chromosomes, based on In 1977. - Frederick Sanger’s observations of mutant fruit flies method determined the DNA bjelooke. sequence of the E. coli bacterio- 1911.- Swede Nilsson-Ehle phage known as the indication of establishes the basis and nature Figure 4 Genes carry the codes for the X174 (which contains 5375 nucle- of inheritance of quantitative protein synthesis otides). Independently of this characteristics. He noticed that that is transferred from bacteria to experiment, by the same principle, their genetics can not explain the bacteria. Walter Gilbert and Alan Maxam current Mendelian rules and raises In 1931. - ‘’ Crossing over ‘’ is developed their methods of chem- the hypothesis of multiple alleles the result of recombination. ical degradation (chemical deg- with cumulative effects and their radation method - Maxi-Gilbert effect on certain genes. He assumes 5. Molecular genetics method). that there a larger number of genes In 1983. - Kary Mullis dis- whose expression is significantly 1941 - Edward Lawrie Tatum covers polymerase chain reac- affected by environmental factors. and George Wells Beadle con- tion (PCR), which enables simple Johansen defines modifications, firmed that genes carry the codes amplification of the DNA molecule. ie. That the phenotypic variation for protein synthesis. within the same genotype is sig- 1944: The Avery–MacLeod– 6. Genomics nificantly influenced by environ- McCarty experiment isolates DNA mental factors. as the genetic material (at that time 1989 - Established the first 1913th - Alfred Sturtevant, called transforming principle). human genome sequence, Francis (Morgan student) announces the 1950: Erwin Chargaff shows Collins and Lap-Chi-Cui (Lap- first gene (genetic) folder chro- that the four nucleotides are not Chi Cui); gene encoding ‘’ CFTR mosomes. He took advantage present in stable proprotions in ‘’ protein, which causes cystic of a phenomenon and related nucleic acids, however certain fibrosis. genes to a gene map, and proved rules appear to hold(e.g., that the In 1994. - He showed up linear arrangement of genes on amount of adenine, A, tends to be FlavrSavr genetically modified chromosome. equal to that of thymine, T). tomato, which he has a long shelf 1918th - Ronald A. Fisher pub- 1952: The Hershey–Chase life. This is the first GM product lished a paper entitled “Correlation experiment reveals that the genetic sales in the United States. GM between members of the same information of phages (and, by tomato puree goes on sale in the family based on Mendelovskog implication, all other organisms) UK in 1996. inheritance ‘’. is DNA. 1995: The genome of bacte- In 1926. - Hermann Joseph 1953: DNA structure is rium Haemophilus influenzae is the Muller reveals, and in 1927 pub- resolved to be a double helix by first genome of a free living organ- lished data on mutagenic effects James Watson and Francis Crick. ism to be sequenced of X-rays. In 1919, Muller real- 1956: Joe Hin Tjio, while 1996: Saccharomyces cerevi- ized two experiments with differ- working in Albert Levan’s lab, siae , a yeast species, is the first ent doses of X-rays were used by established the correct chromo- eukaryote genome sequence to be CESO. She appeared significant some number in humans to be 46. released, and after that of plant, quantitative relationship between 1958: The Meselson–Stahl Arabidopsis thaliana and fruit fly, radiation and deadly mutation. experiment demonstrates that DNA Drosophila melanogaster. (2000.). Muller’s discovery caused a huge is semiconservatively replicated. 1998: The first genome media sensation after a paper enti- 1961. - The genetic code con- sequence for a multicellular tled “The Problem of Genetic sists of triplets; which each consist eukaryote, Caenorhabditis elegans, Modification ‘’ sent to the Fifth of three units (“letter”), each of is released. International Congress of Genetics which encodes one amino acid 2001: First draft sequences of (Berlin). He discovered and struc- only. More codes can have the the human genome are released tural chromosomal mutation that same meaning - encoding the same simultaneously by the Human was later referred to as chromo- amino acids. Genome Project and Celera somal inversions. In 1964. - Howard M. Temin Genomics. In 1927. - Hermann Joseph RNA viruses demonstrates that 2003 (14 April): Successful Muller defines: Physical changes Watson’s central dogma does not completion of Human Genome in genes are called mutations. take into consideration the fact Project with 99% of the genome In 1928. - Frederick Griffith that the viral genetic information sequenced to a 99.99% accuracy. discovers a hereditary molecule can come in the RNA molecule,

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GENETICS ON CRIME SCENE Damir Marjanović, Adna Ašić, Larisa Bešić FORENSIC GENETICS

genetics. Forensic genetics is the sci- entific area of genetics which is concerned with the application of the genetic findings in court, legal procedures. It is important to emphasize that forensic genet- ics, i.e., its foundations, date from before the first official use of foren- sic DNA analysis in 1985. Before DNA analysis, different genetic systems, such as HLA (human leu- kocyte antigen) analysis or ABO blood groups analysis were widely used, especially for the purpose of paternity testing. Moreover, pater- nity testing which was done using comparative analysis of those phenotypic characteristics whose expression was, as it was thought Figure 1 Connection of the forensic genetics with the other at that time, based on the variations scientific fields. of the genetic markers, should not be neglected. The science from Half of the century after the rev- located on the specific positions in that time, at least on the level of olutionary discovery of the molec- the human genome, which repeat its application, is hardly compara- ular structure of DNA as an essen- in successive series. Also, he con- ble to its recent scope. However, tial carrier of hereditary informa- firmed that the number of those some of the fundamental findings tion, it has been promoted into the repetitive units can vary among that still represent the base of the mostly mentioned and used organic the individuals in the examined modern forensic genetics were dis- substance in a wide range of sci- population sample. By improving covered in that period. entific disciplines (Marjanović et the methods of length variations Forensic genetics is based on al, 2005a). One of the most com- analysis of these repetitive DNA the complex interaction of a huge monly used methods of the analy- sequences, Jeffreys created the pos- number of scientific fields, such as sis of individual regions of DNA is sibility to conduct massive human biology, biotechnology, genetics forensic DNA testing, also known DNA testing. (especially population and molec- as DNA fingerprinting or DNA That massiveness, as well as ular genetics), biochemistry, math- typing, depending on the method very high level of applicability of ematics, biostatistics, medicine, of analysis. the newest findings, which consid- technology, law, ethics, etc. (Figure DNA typing has been scientifi- erably overcame the initial postu- 1). cally promoted in forensics 20 years lates of DNA analysis, led to the Today, DNA analysis has an ago in the papers of English geneti- development of the new scientific irreplaceable role in the foren- cist Alec Jeffreys. He described the discipline which is still described sic science as a whole. In the last existence of the DNA sequences, under its working title as forensic twenty years, this method was the

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Almost every scientific discipline has its own heroes who substantially influenced its further development. Forensic genetics is one of the rare scientific disciplines in which even antiheroes had a significant impact through raising public awareness about the necessity of DNA analysis and the need for the investment in this promising tool. Therefore, any forensics text „worth reading“ should not avoid the following three cases: Colin Figure 2 Inner Aspects of the Human Skull Pitchfork Case, O. J. Simpson Case and Bill Clinton Case. We are strongly recommending you to Wenceslaus Hollar, 1651, after Leonardo Da read something about those stories. That will help you to recognize how exact application helped in Vinci the shaping of the forensic genetics as one of the most applied scientific branch within 21st century. main tool that clarified numerous principles are widely used in the in 1980, Alec Jeffreys (Figure 2) forensic cases worldwide. There forensic genetics. showed that specific regions of are several main areas of DNA Final demystification of the DNA (VNTR – variable number of analysis application in forensic molecular structure of DNA which tandem repeats) contain repetitive medicine: investigation of criminal was first shown by the Nobel Prize sequences which differ from person activities, identification of persons, winners James Watson and Francis to person in 1984, and used them and proving the parenthood. Crick in 1953 opened new hori- in the court for the first time a year This method played a very zons in the molecular microcos- later. This discovery was crucial in important role in the Balkans mos. Soon after that, Coenberg dis- solving the first forensic case that thought the projects of the war covered and described DNA poly- used DNA analysis. After the assas- victims identification, both in merase in his papers (in 1958). sination of two girls, Lynda Mann Bosnia and Herzegovina (1992 Twenty years later, Botstein and and Dawn Ashworht, in 1983 and - 1995) and in its closest neigh- his coworkers laid the founda- 1986, police organized the testing borhood. Applying this powerful tions of the RFLP method (restric- of more than 5000 men and finally “molecular weapon”, thousands tion fragment length polymor- found the murderer (Wambaugh, of human remains were given phism) by describing the possi- 1989). However, the discovery of their names back and their fami- bility of using restriction endo- PCR (polymerase chain reaction) lies were at least given the oppor- nucleases, and also showing that procedure and its improvement tunity to bury their loved ones in there are small variations in hered- during the 1980s (Mullis and col- dignity. itary material which differ from leagues, Figure 2-a) significantly The development of the scien- person to person. Finally, after influenced the future of DNA anal- tific field such as forensic genet- Wyman and White described the ysis, both in clinical and forensic ics is not exclusively conditioned existence of short, highly variable medicine. With the discovery of by the events and changes within DNA markers for the first time this technology, it became possible its field of interest. It is necessary to consider all the events that hap- pened prior to its establishment, as well as everything that, originating from the other scientific fields, had either direct or indirect influence on the streams within the forensic genetics itself. The whole book, and not to mention a single chapter like this, would not be enough to consider all the relevant facts, but, however, few of them are worth to be pointed out in this short review. As it is well known, Mendel formulated the basic principles of the inheritance. Even though his first results were published in 1865, they were completely for- gotten until 1900, when the other scientists (De Vries, Correns, and Von Tschermak) confirmed them. a) b) William Bateson (founder of the terms “gene” and “genetics”) in Figure 2 The basis for the “dramatic” expansion of forensic genetics in the last three 1906, proved Mendel’s laws in his decades was set by two scientists who were not forensic experts; a) Kary Mullis who experiments on animals. The foun- defined polymerase chain reaction and b) Sir Alec Jeffreys who performed the first dation and universality of Mendel’s official DNA analysis whose results were verified in the court trial in 1980s.

BurchGene Magazine | May 2016 10 History of Genetics to analyze the biological specimens biological relations between indi- the following 15 years. In 1993, which contain minute amounts of viduals, as well as biological traces. the analysis of already mentioned DNA. This method enabled the probabil- STR loci was introduced for the These fundamental discoveries in ity of tested parentage to cross the first time. Two years later, the first genetics dictated the trend of their limit of 99%. However, its appli- ABI 310 capillary genetic analyzer application, which, in turn, con- cation was still extremely limited was officially produced, as well as ditioned the development of the on the analysis of large biological TaqGold polymerase, which is still forensic genetics itself. Scientists traces and was using an exception- the most commonly used enzyme were aware of the blood group ally long procedure. in forensic DNA analysis. In this inheritance system and the possi- Also, in the early 1990s, molecular period, the first multiplex STR bility of its application in the deter- genetics techniques based on the systems were developed, which mination of biological (genetic) application of PCR found its wide enable simultaneous analysis of relations between human individ- application in the disputed parent- multiple STR loci (at the end of uals for a long time. With the dis- age testing and in forensic DNA 2012, that number increased to the covery of new serological tests analysis. The main advantage of simultaneous analysis of 18 loci in for Rh, Kell, and Duffy blood this method is the ability to get the one reaction), as well as fast-PCR group systems, and their simulta- billions of copies of the fragment thermocyclers and multi capil- neous application with ABO test, of interest from very small biolog- lary genetic analyzers for simple the power of exclusion has been ical traces, i.e., traces character- and simultaneous electrophore- increased up to 40%. ized by the presence of extremely sis of multiple samples, which In the early 1970s, the limits of the small amounts of DNA, using enables extremely fast processing genetic testing were widened from successive and targeted copying of numerous samples. The shorten- blood typing to tissue typing. The of DNA molecules. This analysis ing of the processing time became molecular bases of this testing were was considerably improved with necessary in the laboratories in the application of so-called HLA the two additional steps, intro- whose primary task was process- (Human leukocyte antigen ) typing. duction Taq polymerase and STR ing the samples for the DNA data- There are many HLA types which (short tandem repeats) molecular bases. Also, at the beginning of this expressed a high level of individ- markers, which will be further dis- century, the expansion in the use ual variation which is “geneti- cussed later on. Finally, the appli- of new markers, like SNPs (single cally controlled” primarily by the cation of this method shifted the nucleotide polymorphisms), which genetic complex located on the power of exclusion in the testing of are expected to enable the progress sixth chromosome. Due to that, disputed parentage to the minimum of chip biotechnology and increase they turned out to be a good tool of 99.999% and enabled the anal- the use of mitochondrial DNA and in disputed parentage testing. The ysis of extremely small biological molecular markers related to the power of exclusion was increased traces characterized by the pres- sex chromosomes, was recorded. up to 80% with the application of ence of minute amounts of, usually Modification of the existing STR HLA typing, and in combination highly degraded, DNA. genetic markers and the creation with serological tests, that power In the end, there is a significant and of miniSTR concepts made it pos- reached almost 90%. However, fast progress in the development sible to analyze extremely small the application of this method has of basic biotechnological methods amounts of highly degraded DNA some serious limitations because which enabled the forensic DNA which is often found in biolog- the analysis requires processing analysis to cross the path from an ical traces. In the last few years, large blood samples that cannot exclusive and complex procedure phenotypization (prediction of the be older than few days, which rep- to the everyday routine procedure basic phenotypic characteristics of resents a serious problem, espe- in only 20 years. Soon after the dis- the person who left certain biolog- cially during the testing of infants closure of the famous PCR princi- ical trace based on the analysis of in the first year of life. ple, at the beginning of 1986, the SNP markers) turned out to be very Finally, in the middle 1980s, dis- first PCR thermocycler was con- interesting and it will be discussed puted parentage testing and deter- structed. It was simulating all the in one of the following chapters. mination of the origin of biologi- conditions necessary for perform- The development of forensic genet- cal traces in forensic analyses by ing the phases of PCR method. In ics is truly dynamic and almost processing the primary carrier of that same year, automatic sequenc- every month new product is offered hereditary traits, i.e., DNA mol- ing was described for the first time, on the market to significantly sim- ecule, has begun. Method used and company Applied Biosystems plify already existing procedures or then, so-called RFLP analysis, introduced the first genetic ana- to give completely new solutions in was giving the results signifi- lyzer – model 370A – on the the field of forensic DNA analysis. cantly better than previous serolog- market. Six years later, the same ical and HLA tests. It was shown company presented the first cap- that the fragments of DNA mole- illary system, which will com- cule are significantly more variable pletely repress genetic analyzers than HLA complex, which made based on the classical vertical poly- them ideal for the determination of acrylamide gel electrophoresis in

BurchGene Magazine | May 2016 History of Genetics 11

BIOMEDICAL ENGINEERING Almir Badnjević, Lejla Gurbeta HISTORY AND PERSPECTIVES and comitment in improvement Biomedical Engineering – past of quality of life, enforces the support of technologically special- In its broadest sense, biomedi- ized personnel, trained into solving cal engineering has been with us for problems in medicine and health centuries, perhaps even thousands – bioengineers. of years. In 2000, German arche- ologists uncovered a 3,000-year- Interdisciplinary is a bedrock of old mummy from Thebes with a biomedical engineering, where wooden prosthetic tied to its foot engineers contribute to the to serve as a big toe. Researchers advancement of knowledge equally said the wear on the bottom surface as medical professions. Biomedical suggests that it could be the oldest engineering is, beside the sustain- known limb prosthesis. Egyptians able and renewable energy sources, also used hollow reeds to look and one of the most rapidly growing listen to the internal goings on of the branches of industry in the devel- human anatomy. In 1816, modesty oped world. The development of prevented French physician Rene Figure 1 Biomedical engineering is a biomedical engineering and its Laennec from placing his ear next young field of engineering and science affirmation has mainly appeared to a young woman’s bare chest, so and is yet to be seen how it will affect the in the last 50 years, first as a result he rolled up a newspaper and lis- world of development in electronic indus- tened through it, triggering the idea In respect with growing popu- try (silicon transistor) while later it for his invention that led to today’s lation, medicine and health care started developing at its own pace. ubiquitous stethoscope. have changed dramatically in the past few decades. Within the In this article, history overview of Throughout history, humans modern health care system, engi- Biomedical Engineering is given have made increasingly more effec- neering involvement is needed in with respect to present state in tive devices to diagnose and treat overcoming challenges in human Bosnia and Herzegovina and future diseases and to alleviate, rehabil- health protection, disease preven- research in this area in the world itate or compensate for disabil- tion, treatment and rehabilitation bearing in mind that Biomedical ities or injuries. Miniaturisation of patients throught introducing Engineering, or Bioengineering, is of diagnostic and therapeutic sophisticated technology in every the application of engineering prin- devices, their lower power con- day use, covering a wide range of ciples and methods in solving prob- sumption, portability and appear- products, from simple bandages to lems in the fields of biology, med- ance of microprocessor enabled the most sophisticated life - support icine and health care. Biomedical their applications in practically all equipment and prothesis. Hospitals engineering is a unique mix of branches of medicine, from X-ray and other medical institutions have engineering, medicine and science imaging devices, cardiac pace- a commitment to take care of all emerged alongside biophysics and maker, antibiotic production tech- kinds of high technology devices medical physics. nology, artificial kidney from the including the hospital information early days, computerised tomog- systems, networks and their safety raphy and magnetic resonance and security. Growing technologi- imaging devices and methods, cal participation in health services up to genomic sequencing &

BurchGene Magazine | May 2016 12 History of Genetics micro-arrays, positron emis- sion tomography and image-guided surgery from the last decades. As medical practice becomes more technologically based, a progressive shift occured in industry to meet the demand, so different specialty areas within the field of biomedical engineering were established, such as bioinstru- mentation, biomechanics, bioma- terials, systems physiology, clini- cal engineering and rehabilitation engineering. As for education, the ear- liest academic programs began to take shape in the 1950s. Their estab- lishment was aided by Sam Talbot Figure 2 Intediscipllinary is bedrock of Biomedical Engineering of Johns Hopkins University, who petitioned the National Institutes In Europe, there are more with more than one implantable of Health for funding to support a than 300 universities having pro- electronic device and these devices group discussion of approaches to grams with content in biomedical will have to learn how to commu- teaching biomedical engineering. engineering. The profession “bio- nicate and adjust their performance Ultimately three universities were medical engineer” is a registered in order not to cause any harm due represented in these discussions: profession in many countries and in to joint action. The next step will The Johns Hopkins University, those where it is not an registered probably be functional tissue engi- the University of Pennsylvania professions, biomedical engineers neering where tissue will be grown and the University of Rochester. are considered to work in an inter- from biological material - cells, These three institutions, along with disciplinary area. placed into the body into the right Drexel University, were among position, and then the function of the first to win important training Biomedical engineering the newly implanted tissue will be grants for biomedical engineer- is a key sector for European com- restored. ing from the National Institutes of petitiveness. It presents a €100 Health. billion-market size. In Europe, At the same time, data 20,000 companies work in this transfer and information process- Biomedical Engineering – present sector. This equates to 575,000 jobs ing in medical applications will and in terms of innovation, this is become more demanding due to Today, medical technol- the first sector in patent applica- increased number of sensors for ogy is essential and unavoidable tions – 10,412 – in 2012. Those measurement or monitoring of for each and every effort to ensure numbers are growing very fast and physiological and biomechanical health and well-being of the pop- the Biomedical Engineering sector quantities, from the surface and/or ulation. Everywhere in the world, is becoming of strategic interest from the inside of the body. but especially in Europe, there is to Europe and other developed an increase of chronic non-com- countries. For instance, the CNN There are two major fields municable diseases partially due to reported in 2014 that BME was of intensive research which will aging of the population and par- the first job in the USA for impact, improve the current results, neural tially due to change of lifestyle to growth and future prospects. interfaces and neuroscience. The sedentary or only lightly active, bad need for neural interfaces fosters nutrition habits and increased level Biomedical Engineering – future development of new biocompat- of stress. However, these new and ible materials for neural prosthe- increased needs of the population For research in biomedi- sis, especially among the nanoma- became generators of the economy, cal engineering, there is no limit terials and nanotechnology. In neu- so that e.g. in the USA, “employ- because humans are demand- roscience, scientists are research- ment of biomedical engineers is ing and would like to extend the ing how the brain works and for projected to grow 27 percent from quality of life and the life itself for processing and understanding the 2012 to 2022, much faster than many years. In the next decades, complexity of all the data acquired, the average for all occupations”. one can expect that research will engineering knowledge is neces- Research and development in the concentrate and bring to the market sary. For better understanding of field of medical technology in devices for restoring the functions the data in neuroscience, fusion of directed to finding optimal solu- of tissue, by more sophisticated imaging modalities is necessary tions for social priorities. implantable electronic devices. In and for better diagnosis, medical the future, there will be patients experts still need better resolution

BurchGene Magazine | May 2016 History of Genetics 13

Environment in the bio- in Bosnia and Herzegovina by published in IFMBE Proceedings medical engineering world is con- helping the government in deter- by Springer Nature. Selected stantly and rapidly changing, the mining the strategic direction papers will be published at CC/SCI knowledge is rapidly increasing related to Biomedical Engineering Indexed Springer Journal. and there is a constant need for and supporting researches in this As for education, different scien- increasing the resources and equip- area. tific curricula exist mostly on facul- ment necessary for the demanding 1st Conference of Medical and ties for electrical engineering and/ research. Biological Engineering in Bosnia or informational technologies on Biomedical Engineering in and Herzegovina (CMBEBIH public and private universites, but Bosnia and Herzegovina 2015), was held in Sarajevo from there are evidences that this field of Field of Biomedical 13th to 15th March, 2015 with formal education is yet to develop. Engineering in Bosnia and goal to “Expand your (own) hori- Biomedical engineering is Herzegovina is very young and zons through biomedical engi- a young field of engineering and still in the first stage of devel- neering”. The organizers, Bosnia science and it is small compared to opment. In 2014, Bosnia and and Herzegovina Medical and the traditional engineering fields, Herzegovina Medical and Biological Engineering Society. like electrical or mechanical engi- Biological Engineering Society 2nd Conference of Medical and neering. However, due to the needs (DMBIUBIH) was established. Biological Engineering in Bosnia of the society and enthusiasms of This society brings together a large and Herzegovina (CMBEBIH young generations of students, the number of university professors, 2017), will be held in Sarajevo from number of biomedical engineers doctors, engineers and technicians 16th to 18th March, 2017. It will working in research and develop- in the field of medical, biological, be exciting, informative and inspir- ment is rapidly growing. electrical, mechanical engineer- ing conference with aim of sharing As for Bosnia and ing, pharmacy and other related ideas, experiences, best practices Herzegovina, Biomedical science fields. The main goal of and latest researches in biomed- Engineering it is yet to be seen this society is to support develop- ical engineering. The good news how research and academic pro- ment of Biomedical Engineering is that all accepted papers will be grammes will develop in future. Don’t miss #cmbebih2017!

BurchGene Magazine | May 2016 14 History of Genetics

SCIENCE ABOUT SMALL

Enisa Omanović Mikličanin NANOTECHNOLOGY

nanometre scale. Nanomaterials are categorised according to their HOW IT STARTED? dimensions as shown in Table 1. Nanomaterials are larger than sin- The ideas gle atoms but smaller then bacteria and con- and cells. Figure 2. visualise the cepts be- relationships between bulk materi- hind nano- als, like a tennis ball, and nanoma- science and nanotechnology terials. Why „nano“ is so special? started with a talk entitled There are various reasons why “There’s Plenty of Room nanoscience and nanotechnolo- at the Bottom” by physicist Figure 1 Physicist Richard Feynman, the gies are so promising in materials, Richard Feynman at an Amer- father of nanotechnology. engineering and related scienc- ican Physical Society meet- Nanotechnology is „the es. First, at the nanometre scale, ing at the California Institute science about small“. It is the the properties of matter change. of Technology (CalTech) on study and application of extreme- This is a direct consequence of December 29, 1959. In his ly small things which can be used the small size of nanomaterials, talk, Feynman described a across all the other science fields, physically explained as quantum process in which scientists such as chemistry, biology, phys- effects. The consequence is that a would be able to manipulate ics, materials science, and engi- material (e.g. a metal) when in a and control individual atoms neering. On of the definition of nano-sized form can assume prop- and molecules. It was a long nanotechnology is that it conducts erties which are very different before the term nanotechnol- science, technology and engi- from those when the same materi- ogy was acctually used. Over neering at nanoscale (1-100 nm). al is in a bulk form. For instance, a decade later Professor No- The same material (e.g., gold) at bulk silver is non-toxic, whereas rio Taniguchi coined the term the nanoscale can have proper- silver nanoparticles are capable nanotechnology in his ex- ties (optical, mechanical, electri- of killing viruses upon contact. plorations of ultraprecision cal etc.) which are very different Properties like electrical conduc- machining, It wasn’t until from the properties the materi- tivity, colour, strength and weight 1981, with the development al has at the macro scale (bulk). change when the nanoscale level of the scanning tunneling is reached: the same metal can microscope that could “see” What is a nanomaterial? become a semiconductor or an individual atoms, that mod- A nanomaterial is an object that insulator at the nanoscale level. ern nanotechnology began.. has at least one dimension in the The second exceptional property

BurchGene Magazine | May 2016 History of Genetics 15 of nanomaterials is that they can be fabricated atom by atom by a process called bottom-up. The information for this fabrication process is embedded in the material building blocks so that these can self-assemble in the final product. Finally, nanomate- rials have an increased sur- face-to-volume ratio com- pared to bulk materials. This has important consequences Figure 2 From a macro-materials to atoms (source: „A snapshot of nanotechnology“ Na- for all those processes that tional Cancer Institute) occur at the surface of a material, such as catalysis and detection. Nanotechnology has broad applications in medicine, cosmetics (e.g., sunscreams), food etc. Application of nan- otechnology in medicine, specially in cancer treatment have brought a new inter- disciplinary research field – nanomedicine. THANKS TO OUR GOLD SPONSOR

BurchGene Magazine | May 2016 16 History of Genetics

A LOVE STORY Elma Ferić Bojić NEUROSCIENCE AND GENETICS

“folded cloth” and a final suffix that brain and spinal cord. In the 1950s means “little” (Figure 1). In fact the and 1960s both Massachusetts glyphs represent sounds that all add Institute of Technology as well as up to a word that approximately Harvard Medical School brought means “skull-offal,” which is not together studies of biology, chem- entirely respectful, but logical, con- istry, physics and mathemat- sidering that the organ was teased ics and became the first to estab- out through the nose and subse- lish free standing Neuroscience quently thrown out upon mummi- departments. fication. Moreover, it was the heart Subsequent advances in tech- that was regarded as the center of nologies in molecular biology and intelligence and thus given a lot genetics and a desire to understand more attention. the link between genes, behavior, Figure 1 Edwin Smith Surgical Papyrus Despite the lack of respect that the brain and neurological disor- and First Symbol for ‘Brain’ was given to the brain, the ancient ders gave birth to a field that com- physician that conducted the exam- bined the studies of neuroscience The brain is the center of inations referenced in the papyrus and genetics, namely neurogenetics thought and emotion, and, essen- was aware of the life-threatening and gave rise to a concept termed tially, the organ responsible for repercussions of injuries to that the ‘Genetic Brain.’ Even though how we perceive the world around organ as well as their unexpected the history of genetics dates back us. Yet it took humans quite some symptoms in the rest of the body. to the late nineteenth century, just time to comprehend the ins and Head injuries that affect people’s a few decades before the purchase outs of the center of their exis- ability to speak and walk as well of the papyrus, a time at which tence. In fact, the first traces of as their visual abilities were also Gregor Mendel published his neuroscience date back as far as mentioned in various cases in the genetic inheritance concepts, neu- 5000 years ago, to a time when text, and the same motor functions rogenetics began to expand in the the ancient Egyptians referred to are tested today as means to inves- 1960s, pioneered by the research of it cryptically. The document that tigate possible brain injuries. Seymour Benzer (Figure 3), who illustrates this fact is termed the utilized the fruit fly to elucidate Edwin Smith Papyrus (Figure 1), The investigations into the brain many neurological functions and named after an Egyptologist who and allusions to it as the center of who is considered by many to be purchased it in 1896 at which time intelligence varied throughout early the father of neurogenetics. it was deciphered to have been history. The Middle Ages produced written in approximately 3000BC. beautiful renditions of the organ No pun intended, but at the heart However, since ancient Egyptians (Figure 2) and indications that of neurogenetics is the study of the from this period did not have a humans’ understanding of the very role of genetics in the development word for the organ, perhaps the tissue they use to think was become and function of the nervous system. papyrus reveals how they did not more advanced are reflected in In this endeavor, neural character- think about the brain. While the events in the twentieth century, istics are considered phenotypes hand, heart and eye each had their whereby universities deemed it and are assumed to be unique to own unique words, the term used to significant enough to justify aca- individuals, even those belonging indicate “brain” is made up of four demic programs strictly devoted to the same species. Staying true glyphs, namely “vulture,” “reed,” to studying the functions of the to its name, neurogenetics draws

BurchGene Magazine | May 2016 History of Genetics 17

“Three pounds of the most complex material that we’ve discovered in the universe. This is the mission control center that drives the whole operation, gathering dispatches through small portals in the armored bunker of the skull. Your brain is built of cells called neurons and glia – hundreds of billions of them. Each one of these cells is as complicated as a city. And each one contains the entire human genome and traffics billions of molecules in intri- cate economies. Each cell sends electrical pulses to other cells, up to hundreds of times per second. If you represented each of Figure 2 Inner Aspects of the Human Skull these trillions and trillions of pulses in your brain by a single Wenceslaus Hollar, 1651, after Leonardo Da Vinci photon of light, the combined output would be blinding.” ~D.E.

aspects from both neuroscience While simpler diseases and dis- which implies that there is more and genetics while it focuses on orders have genetically been pin- to a disease than what exists in the an organism’s genetic code affects pointed, the genetics behind more genetic code. its expressed traits. In other words, complex neurological disorders is a This points to a presently in its dynamic nature, it focuses on source of ongoing research. One of dominant field of study termed the impact of genes on the struc- the new developments that resulted epigenetics, namely an area that ture and function of the brain and in possible elucidations of genetic focuses on the study of reversible peripheral nervous system, which variability within the human pop- heritable changes in the function- means that neurogenetics is a dici- ulation and thereby enabling more ing of a gene without alterations of pline that aims at elucidating those readily discernible linked dis- the DNA sequences. Examples of genes that determine or drive our eases are genome wide association these phenomena are mechanisms individuality including diseases studies (GWAS). And while cur- such as histone de-acetylation and and dysfunctions. rently no reliable treatment para- DNA methylation of non-coding Therefore it is safe to claim digms exist that effectively reverse sequences which induce long-term that mutations in the neurogenetic progressions of neurodegenerative silencing of transcription as a result sequence may have a wide range diseases, further advancements in of environmental events that cause of effects on one’s quality of life neurogenetics might yield to ther- long-term developmental changes and must therefore be studied apeutic drugs that could reverse in chromatin structure. This, in closely. The earliest studied dis- brain deterioration. turn highlights the present view of eases include amyotrophic lateral the dynamic and thereby complex sclerosis (ALS), Alzheimer’s and However, despite the fact that field of neurogenetics that is that Huntington’s, and they are still at there are an increasing number of the brain, more than any other the center of much research con- genetic polymorphisms that are organ, is under strong social and ducted today. The contribution of studied, they still lack to fully environmental influences that can genetics to the understanding of account for much of the variance have long-lasting effects on brain cognition and psychiatric disor- seen in many psychiatric illnesses function and wellbeing. ders has tended to focus on gene and thereby point to gene-envi- polymorphisms, or the function- ronment interactions that have the But how lucky are we to live in ally silent differences in DNA frag- ability to account for much more a time of rapidly advancing tech- ments that are responsible for the of the causes and origins of psy- nology that enables us more so vast variation in our species, that chiatric disorders. A powerful than ever to comprehend the inner enabled linkage testing, or the anal- example of this idea is schizophre- workings of the very organ that we ysis of the linkage between DNA nia, a disease that affects how an use as we attempt to comprehend and gene defects. Furthermore, individual feels, thinks and acts. it?! How is that for a mind blow, advancing technology made Those who are affected typically brain twister, mind teaser? genetic analysis more feasible and have a difficult time distinguish- available, which is why the last ing between what is real and what decade of the 20th century was is imagined and with expressing marked by an increase in identi- normal emotions in social situa- fying genetic roles in neurological tions. The cause of the disease is disorders. These advancements still mainly unknown, and while it included, among many, disorders is only 50% concordant in genet- such as Parkinson’s, Alzheimer’s, ically identical twins, the severity Fragile X syndrome, epilepsy as of different life-events may predis- well as ALS. pose some people to certain psychi- Figure 3 Seymor Benzer and a atric disorders more so than others Drosophila BurchGene Magazine | May 2016 18 History of Genetics

FROM GENES TO THERAPY

Adnan Fojnica GENE THERAPY Understand the gene therapy Gene therapy is a type of bio- logical therapy that involves alter- ing the genes inside body’s cells, usually by introducing nucleic acid polymers in order to threat specific disease. Hereditary units founds on DNA, are called genes. They control much of our body’s shape and function, from making color of our eyes to regulation of complete body systems. If genes don’t work properly, they can cause disease. Gene therapy seems like ideal solu- tion for treating a wide range of Figure 1 Inserting the vector in gene therapy diseases, including cancer, cystic fibrosis, heart disease, diabetes, to as transfection. recombinant DNA technology in hemophilia and AIDS. Right now, the most commonly the 1970s, the tools to efficiently Basically, gene therapy replaces used vector, genetically altered to develop gene therapy become a faulty gene or adds a new gene carry normal human DNA is virus. available. Scientists used these in order to cure disease or improve Viruses have evolved a way of techniques to isolate genes, our body’s ability to fight disease. encapsulating and delivering their A carrier molecule (called vector), genes to human cells in a patho- must be used to deliver the correct genic manner. Scientists have gene to the patient’s target cells. used this capability and manipu- There are two general approaches late the virus genome to remove for introducing genes into a cell: disease-causing genes and insert viral and nonviral. Viral vectors therapeutic genes. have been used in ~70% of the clinical trials to date. Viral vectors Walking through history are extremely efficient at trans- ferring genes but can create some The concepts of gene therapy Figure 2 Dr. Kenneth Culver W. French safety risks. Gene transfer medi- first time appears during the 1960s Anderson, and Michael Blaese pose with ated by viral vectors is referred to and early 1970s, in the same time as gene therapy patients as transduction. Nonviral vectors experiments of genetically marked identify mutations involved in are considered to be much safer cells lines and the elucidation of human diseases, manipulate viral than viral vectors, but at present, mechanisms of cell transformation genomes characterize and regu- they are fairly inefficient at trans- by the papovavirus and SV40 was late gene expression, and engineer ferring genes. Gene transfer medi- in progress. various viral vectors and non-vi- ated by nonviral vectors is referred With the discovery of ral vectors. BurchGene Magazine | May 2016 History of Genetics 19 Gene therapy first barrier appeared in the early 1970s, when the term “gene surgery” was first introduced. In 1972, Richard Roblin and Theodore Friedmann pub- lished a paper in Science called “Gene therapy for human genetic disease?” which is cited version of Stanfield Roger’s proposal from 1970 that “good DNA” could be used to replace defective DNA in people with genetic disorders . In 1983, a group of scientists from Houston, Baylor College of Medicine and Texas, proposed that one day, gene therapy could Figure 3 Seeing into the future of vision therapy, doctors say they can use gene be a viable approach for treating therapy to reverse blindness. Lesch-Nyhan disease, a type of “marked TIL cells” helped the several types of immunodeficiency rare neurological disorder. Namely, researchers learn two things: engi- diseases, cancer, and eye disorders. this group of scientists conducted neered virus can be used safely in many experiments in which an humans and which TIL cells work Problems and Prospects enzyme-producing gene for cor- best for cancer treatment. recting the disease was injected Finally on September 14, 1990 Since the first clinical gene-therapy into a group of cells. Based on this, at the NIH Clinical Center, four- trial was conducted (Rosenberg et researcher theorized the cells could year old girl became the first gene al., 1990), much attention and con- then be injected into people with therapy patient, after her nine-year siderable promise has been given the Lesch-Nyhan disease. old girl. They had adenosine deam- to the field. There has been sub- In 1985, dr. W. French Anderson inase (ADA) deficiency, a genetic stantial public- and private-sec- and Michael Blease joined their disease which leaves her defense- tor investment, as well as increas- knowledge in order to demonstrate less against infections. White blood ingly higher levels of research how cells from people with ADA cells were taken from her, and the activity. Numerous preclinical deficiency could be modified in normal genes for making adenos- animal-model studies have pro- tissue culture. They used a retro- ine deaminase were inserted into vided proofs of concept for mul- virus as a vector to carry the correct them. The corrected cells were tiple potential clinical applica- ADA gene into the cells. reinjected into her. Each girl was tions. Also, major advances have In 1986, they tried transferring the given repeated treatments over a been made in understanding vector correct genes into the bone marrow period of two years. Dr. W. French biology and improving vector of animals, but in 1988, found that Anderson helped develop this land- design and production. transferring them to white blood mark clinical trial when he worked However, clinical progress has cells was much more successful, at the National Heart, Lung, and been slow. A major setback for the with a dramatic increase in the Blood Institute. field occurred in September 1999, amount of the correct genes being The development of suitable when a widely publicized death taken up by cells, even if number gene therapy treatments for many resulting from a gene-therapy trial of them wasn’t still enough. genetic diseases and some acquired was reported, Jesse Gelsinger, an 1988 - The scientists decided to use diseases has encountered many 18-year-old man, died in a clin- white blood cells (T cells), in tissue challenges and uncovered new ical trial at the University of culture, instead of bone marrow insights into gene interactions Pennsylvania, which used a modi- cells. This switch greatly increased and regulation. Further develop- fied Ad5 vector to deliver the gene the number of correct genes taken ment often involves uncovering for ornithine decarboxylase, a defi- up by the cells in the animal exper- basic scientific knowledge of the cient hepatic enzyme. iments. The experiments were so affected tissues, cells, and genes, Fortunately for the gene therapy successful that the team began to as well as redesigning vectors, for- field, less than 1 year after look for ways to test the delivery mulations, and regulatory cassettes Gelsinger died, the first report of a system in people. for the genes. dramatically successful gene-ther- In 1989, the researchers teamed While effective long-term treat- apy trial was published. In 2000, up with Dr. Steven Rosenberg, ments for anemia, hemophilia, Cavazzana-Calvo and her col- to test how safe and effective the cystic fibrosis, muscular dystro- leagues in Paris described results gene therapy would be in cancer phy, Gauscher’s disease, lyso- from a study involving two children patients. The team cultured tumor somal storage diseases, cardiovas- suffering from a severe combined infiltration lymphocytes cells from cular diseases, diabetes, and dis- immunodeficiency disorder (SCID- people with malignant melanoma eases of the bones and joints are XI), which had restricted them to and manipulate a virus to put a elusive today, some success is life in an isolated environment. DNA marker into those cells. These being observed in the treatment of

BurchGene Magazine | May 2016 20 History of Genetics

IS ALZHEIMER’S IN YOUR GENES?

Džana Mulaomerović ALZHEIMER´S DISEASE These symptoms occur because the early damage in Alzheimer’s is usually in hippocampus, part of a brain that has major role in day- to-day memory. Memory for life events that happened a long time ago is often unaffected in the early stages of the disease. Because of memory loss, person may have everyday difficulties such as: lose items around the house, struggle to find the right word in a conver- sation, forget names, forget about recent conversations or events, and forget appointments or anniversa- ries. Individuals with Alzheimer’s also have, or would develop prob- lems with other aspects of think- ing, reasoning, perception or communication. Figure 1 If you have a brain, you are at risk for alzheimer The genetics of disease Alzheimer´s disease is a degen- of memory, paranoia and shrink- erative disease of brain that results age of the brain. Psychiatrist The second most import- in dementia or loss of memory, Emil Kraepelin coined the term ant cause of the disease is family judgment, and ability to function. “Alzheimer’s disease” in a medical history. Twin and family studies The disease usually affects indi- book in 1910. By this time several suggest that genetic factors may vidual older than 65 but it is not more cases with similar symptoms play a major role in at least 80% of a normal part of aging although were reported. In 1976, the neurol- AD cases. Certain genes make you it is one of the major risk factors. ogist Dr. Robert Katzman declared more likely to develop Alzheimer’s Alzheimer’s is considered to be a AD the most common form of disease, however, genetic risk cause of 60 to 80 % of all dementia. dementia which brought aware- factors are just one of the factors ness to the disease. involved in getting Alzheimer’s The discovery of Alzheimer’s disease. disease (AD) Symptoms of Alzheimer’s AD is caused by any one of a number of different single-gene AD is named after German For most people with mutations on chromosomes 1, 14 doctor Alois Alzheimer. The first Alzheimer’s, the earliest symptoms or 21. These mutations involve case of Alzheimer’s was reported is memory loss. Patients may have the gene for the amyloid precur- by Alois Alzheimer in his patient difficulties recalling recent events sor protein (APP) and the genes whose symptoms included loss or learning new information. for the presenilin 1 and presenilin

BurchGene Magazine | May 2016 History of Genetics 21

Alzheimer’s statistics •Nearly 44 million people have Alzheimer’s or a related dementia worldwide •Only 1 in4 people with disease have been diagnosed. •Alzheimer’s disease is listed as the sixth-leading cause of death in the U.S. •Alzheimer’s is most common in Western Europe •The cost of caring for Alzheimer’s patients in the U.S was $226 billion in 2015 •Life expectancy after an Alzheimer’s is diagnosed is 4 to 8 years. •2 in 3 people with Alzheimer’s disease are women.

2 proteins. Each of these muta- disease can be prevented, slowed tions causes abnormal proteins for- Treatment of Alzheimer’s or stopped. Scientists believe that mation. Individuals with muta- early detection is key to preventing, tions in any of these three genes U.S. Food and Drug slowing and stopping Alzheimer’s tend to develop Alzheimer’s symp- Administration (FDA) has been disease. toms before age 65, sometimes in approved 6 medicines to treat the Studies suggest that major early 30s, while majority of people disease. The drugs temporarily causes of Alzheimer’s include a with Alzheimer’s have late-on- improve symptoms of Alzheimer’s combination of genetic, environ- set disease, occurring at age 65 disease by increasing the amount of mental, and lifestyle factors that or later. Early-onset Alzheimer’s neurotransmitters in the brain. The affect a person’s risk for develop- disease occurs in people age 30 to effectiveness of the medicines vary ing the disease. 60 and counts for 5% of all indi- from person to person but none of Studies also suggest that viduals with Alzheimer’s. them stops the damage to neurons people with fewer years of formal caused by disease. education are at higher risk for Chances of getting AD Alzheimer’s and other demen- tias than those with more years Alzheimer disease is inherited of formal education. Some scien- in an autosomal dominant pattern. tists believe that having more years Individuals inheriting a mutation of of education makes a “cognitive APP or presenilin 1 genes are guar- reserve”. The cognitive reserve anteed to develop Alzheimer’s. A hypothesis suggests that having child whose biological mother or more years of education increases father carries a genetic mutation the connections between neurons for early-onset FAD has a 50/50 which enables brain to compen- chance of inheriting the same sate for the early brain damages mutation. If the mutation is inher- Figure 3 Seymor Benzer and a of Alzheimer’s by using alternate ited, the child has a very strong Drosophila routes between neuron commu- probability of developing early-on- nications to complete a cognitive set FAD. Those inheriting a muta- tasks. tion in the presenilin 2 gene have According to World Health a 95% chance of developing the Even though Alzheimer’s Organization, number of people disease. But not everyone who has disease was first identified more living with dementia will triple till mutations is getting Alzheimer’s, than 100 years ago, more than 70 2050. Alzheimer’s kills more than and this suggest that other genetic years passed before it was recog- breast and prostate cancer com- and environmental factors are nized as potential “major killer”. bined. Efforts to cure the disease likely involved in development of The disease begins before any include Alzheimer’s disease disease. Researchers indicate that symptoms can be noticed. Research Sequencing Project and wide range many more genes that haven’t been has revealed a lot about disease, but of genomic studies, but till the time identified yet could affect the risk much more has to be discovered we found answers, everyone with of development of Alzheimer’s about the precise biologic changes a brain is at risk for Alzheimer’s. disease. that cause Alzheimer’s, and how

BurchGene Magazine | May 2016 22 History of Genetics

A,C,G & T

Anis Čilić BIOINFORMATICS A, C, G & T are ‘’letters’’ that solve some of the crucial questions analyse date obtained from Human write ‘’book of life’’ inside each in life science and lay a foundation Genome Project and other genome of us. It took too long for humans of science which, today, play great sequencing, and also to discover to decipher these ‘’letters’’ and role in genetics, medicine, crimi- new information from existing start reading ‘’book of life’’ nalistics, etc. data. which keeps secrets inside them. Let’s take a look on the some Begining of this process is con- So, what is bioinformatics? of the most important events that nected with the development of contributed to developement of technology. After World War II, Bioinformatics is scienece bioinformatics: technology, which was used mostly which uses knowledge from One of the main landmark in military puproses, became avail- biology, computer science and discoveries was prediction of the able for scientists. Many scientific statistics to analyze different data duoble helix for DNA by Watson & fields starts to implement technol- such us sequences of nucleic acids Crick in 1953. Their work helped ogy in their researches. Progression and proteins, gene expression data, us in understanding genetic struc- of technology, especially comput- different molecular pathways and ture and human genome and served ers, leads to rapid development of nowdays different clinical data as basis for later genomic studies. science. These technological ino- also. In 1955 first protein sequence vations allowed more precise and Development of bioinformat- (bovine insuline) was analyzed more detailed analysis of organis- ics was due to huge amount of data by Frederick Sanger. This dis- ams and species and microworld created by frequent sequencing. covery earned him Nobel prize in and it’s secrets start to appear... These data were able to be stored Chemistry in 1958. This was the Information was accumulating and analyzed only by computer. begining of ‘’sequencing journey’’ as new researches were done. It The main purpose of the bioin- which will leave a mark on a became imposible for human brain formatics is to store, compere and science and change it’s perspective. to store, follow and process all these things, so artificial memory came to the fore. With the usage of computers, science developed rapidly and thus science was divid- ing in some new fields. Biology, informatics and statistics combined together in one field to form bio- informatics, which, for the first time, appeared in literature in 1991 (although there are some records that this term was used in conver- sation in 1985). Although the founders of this science did not use term ‘’bioin- formatics’’ to describe their field of work, they knew how to make most of computer technology, mathe- Figure 1 Huge amount of data created by frequent sequencing were able to be matics and biology and on that way stored and analyzed only by computer.

BurchGene Magazine | May 2016 History of Genetics 23 Sanger’s work led other research- ers to sequence different proteins, so in 1965, Margaret Dayhoff published initial edition of the Atlas of protein sequences. It is the first public database of protein sequences wihch consisted of totally 65 protein sequences that were listed in the Atlas. This study played important role in develop- ing of bioinformatics and data- bases such as GenBank. During the year 1965, other great work was done, Robert Holley published first sequence of RNA (alanine tRNA from Saccharomyces cer- evisiae) and beat Sanger in com- petition to be first who publish RNA sequence. But it did not take to long for Sanger to sequence RNA, in 1967, Sanger and group of his co-workers published the sequence of the 5S ribosomal RNA Figure 2 Intediscipllinary is bedrock of Biomedical Engineering from E.Coli. Researchers con- tinue to make effort in the field of sequencing, so by 1970 first algo- rithm for sequence alignement and comparision was created by Needleman-Wunsch. While biolo- Figure 2 That’s how Sanger sequencing works gists/geneticists were putting a lot and information was amassing, make-up the World Wide Web of effort in sequencing, computer first databeses started to appear. which allowed sciencist to reach engineers achieved great results In 1986 SWISS-PROT database all new analysis, data, reseaches in their researches. In 1969, first was created. Same year, word from all around the world. packet swithing network named ‘’Genomics’’ appeared for the first 1990s are years of genome sequenc- ARPANET was created. This work time to describe the scientific disci- ing. During this period first genoms was one of the techincal founda- pline of mapping, sequencing, and are sequenced: in 1995 bacteria tion to the Internet, which firstly analyzing genes. The 1988 was genome & in 1996 first eukaryotic appeared in 1974, when Vint Cerf turbulent year: NCBI was estab- genome of Saccharomyces cerevi- and Robert Khan developed the lished at National Cancer Institute siae. All resources were invested concept of connecting networks and then Human genome organi- in sequencing of human genome, of computers. In 1975 Bill Gates sation (HUGO) was founded. This and first large achivement was and Paul Allen founded Microsoft year was also significant because in 1999 when first human chro- Corporation. FASTA algorithm for sequence mosome was sequenced. HGP On the other side, Sanger and his comparision is pubished, and one was large investment - estimated colleagues continued research in of the most important project in costs were 1$ per base pair, and sequencing, they tried to obtain history of bioinformatics was ini- costs of HGP reached 2,7 billion novel DNA sequencing method tiatet - HGP (Human Genome $. Fifty years after Watson’s and which will allow sequencing of Project). Crick’s landmark discovery, human larger segments of DNA. Novel Human DNA sequence was genome sequence was compleated method for sequencing DNA known unknown for a long period of time. and journey through ‘’book of life’’ as Sanger method was published Great effort was made in sequenc- was started. in 1977. Discovery of this method ing human genome, and finally, in Although great work was done and earned Sanger second Nobel prize 1990, HGP officialy begin and bio- large amount of data has been pub- in Chemistry in 1980. All of this informatics started to gain attention lished, there are a lot more to do and led to publication of first com- in a large scale. Same year BLAST improve in this field. Nowdays bio- plete gene sequence of and organ- program is implemented and this informatics has important role and ism (phage) in 1980. One year later allowed sciencists to compare is increasingly interconnected with Smith and Waterman created algo- sequences (nucleotide or protein) medicine. Many researches were rithm for sequence alignment and and find matches between differ- done and data was obtained, and during the same year IBM intro- ent organisms.Major milestone now is bioinformatics turn to find duced Personal Computer to the occured in 1991 - the research correlation between all these data market. institute in Geneva announced the and offer appropriate solutions. As new researches were performing creation of the protocols which

BurchGene Magazine | May 2016 24 History of Genetics

A TRIP DOWN MEMORY LANE Dijana Sejdinović MOLECULAR GENETICS The history of molecular genet- enzyme that catalyzes a quite differ- deoxyribonucleic acid (DNA). This ics is very rich and colorful in the ent reaction in the general metab- principle, obtained from dead bac- events as well as characters that olism of the cell (heterocatalysis). terial cells of one strain, was shown contributed to its development. In 1928, scientists didn’t know to transfer a characteristic from that Before talking about the history it yet that DNA carried genetic infor- strain to another strain. This extract is important to understand the term mation, but they knew that there contained only the minutest traces of molecular genetics. Genetics is was something that could cause of protein; the rest was DNA. not made up of two sciences, one bacteria to transform from one type Geneticists knew about this work, molecular and one non-molecular to another. Griffith’s experiment but the majority assumed that the even though the term molecular is was the first experiment suggesting DNA was acting as a mutagen, still widely used among scientists. that bacteria are capable of trans- altering the genetic constitution of Molecular genetics is an investi- ferring genetic information through the recipient cell, not transferring gative approach that involves the a process known as transformation. a gene. application of laboratory methods Griffith’s findings were followed Making the case for DNA and research strategies. This by research in the late 1930s and acting as the repository of the approach presupposes basic knowl- early 40s that isolated DNA as the genetic specificities of the organ- edge about the expression and material that communicated this ism called for establishing the kind regulation of genes at the molec- genetic information. of structure DNA possesses that ular level. Philosophical interest The protein nature of the would permit it to function thus. in molecular genetics, however, gene was called into question in Known to be a long-chain mole- has centered, not on investigative 1944 when three Rockefeller sci- cule, its backbone composed of approaches or laboratory methods, entists, Ostwald Avery, Colin sugar rings attached to one another but on theory. Early philosophical MacLeod, and Maclyn McCarty, by phosphate arms, it has only research concerned the basic theory published their identification of the four kinds of side-groups attached about the make-up, expression, and so-called transforming principle as to the sugars—the bases adenine, regulation of genes. The first half of 20th century is often referred as classical genet- ics. Morgan had set the tone, treat- ing the gene as an abstraction and the Mendelian analysis of exper- imental data as an algorithm. In 1922 Muller had drawn the analogy between bacterial viruses and genes. During this period a concern of identifying gene products chem- ically has continued. Nonetheless, the chemical constitution of the gene remained vague, and geneti- cists were content to assume it was a protein of a special kind: one that can both catalyze its own reproduc- tion (autocatalysis) and provide an Figure 1 The Avery–MacLeod–McCarty experiment

BurchGene Magazine | May 2016 History of Genetics 25 does not use the most mathemati- cally elegant solution. The amino acid sequences being discovered in proteins showed no limitations on the permutations of nearest neigh- bors of the kinds required by these mathematical codes. Therefore is the need to turn to the biochem- ists and the geneticists to solve the problem. They attacked it with vigor, and by 1966 the full details of the code were established. But the major transformation of genet- ics came with the introduction in the 1970s of the techniques of recombinant DNA technology that made directed manipulation of the genetic material possible. In 1972, Walter Fiers and his team at the University of Ghent were the first to determine the sequence of a gene: the gene for Bacteriophage MS2 coat protein. Richard J. Roberts and Phillip Sharp discov- ered in 1977 that genes can be split into segments. This led to the idea that one gene can make several proteins. The successful sequenc- ing of many organisms’ genomes has complicated the molecular definition of genes. In particular, Figure 2 Watson and Crick – discovery of DNA double-helix genes do not seem to sit side by side on DNA like discrete beads. guanine, thymine, and cytosine. it offered crucial support. Yet it was Instead, regions of the DNA pro- This contrasts unfavorably with not until 1958 that evidence from ducing distinct proteins may the proteins, for they have twenty quite different approaches was overlap, so that the idea emerges different amino acids that can be published confirming predictions that “genes are one long contin- arranged in countless different made from the model. Only then uum”. It was first hypothesized in sequences. did interest in the structure become 1986 by Walter Gilbert that neither The proposal of the double-helical widespread. DNA nor protein would be required model of DNA by James Watson In genetics the work of Sydney in such a primitive system as that and Francis Crick in 1953 over- Brenner, Francis Crick, Leslie of a very early stage of the earth came this difficulty because their Barnett, and R. J. Watts-Tobin, if RNA could perform as simply structure, a cylindrical one with the using mutagenesis in bacteriophage a catalyst and genetic information four kinds of bases packed inside to establish the general nature of storage processor. the two helically entwined sug- the genetic code, was published While these discoveries set the ar-phosphate backbones, permits in 1961. It marked a success in tone for scientist all over the world any kind of sequence of the bases. applying the genetic approach to and started a race for research Moreover, these bases are paired by questions at the molecular level, and development of molecular weak bonds across from one base to for they showed that the genetic genetics, the best is yet to come. its opposite number, adenine with message is composed of triplets Everyday technology is progress- thymine, guanine with cytosine. of bases, read from a fixed start- ing and opening new possibilities Watson and Crick therefore visu- ing point, in only one direction, and for improvements and new con- alized the duplication of the gene without commas between the trip- cepts especially because the molec- as the result of separating the two lets. Meanwhile biochemists had ular genetics is based on laboratory chains of the parent double helix been establishing the identity of the techniques. When we are talking and attaching free bases to those amino acids coded by given triplet about history of molecular genetics now unpaired in accordance with sequences of bases. we can surely say that because of the above complementary relations. It was the physicist George Gamow fast development and big interest, The work of Rosalind Franklin and who had first suggested a DNA code the ideas that are currently unimag- Maurice Wilkins in London had for the amino acids in proteins. He inable are soon going to become not only aided Watson and Crick had hoped the right code could be history. in devising their proposed struc- established by mathematical rea- ture, but when published alongside soning but had to accept that nature BurchGene Magazine | May 2016 26 History of Genetics

9 GREATEST DISCOVERIES

Ahmed Osmanović GENETIC TIMELINE

1865-1865-Heredity Heredity 2TransmittedTransmitted inin UnitsUnits Gregor Mendel, through his work on pea plants, discovered the fun- damental laws of inheritance. He deduced that genes come in pairs and are inherited as distinct units, one from each parent. Mendel tracked the segregation of paren- tal genes and their appearance in the offspring as dominant or reces- sive traits. He recognized the math- ematical patterns of inheritance from one generation to the next. After his death, Mendel’s personal papers were burned by the monks. Luckily, some of the letters and doc- uments generated by Mendel were kept in the monastery archives.

1859- Natural Selection 1911-1911-Chromosome Chromosomes 1 Natural selection is the CarryCarry Genes Genes process by which species adapt to 3 their environment. Natural selec- Thomas Hunt Morgan and his stu- tion leads to evolutionary change dents study fruit fly chromosomes. when individuals with certain char- By painstakingly examining thou- acteristics have a greater survival sands upon thousands of flies with or reproductive rate than other indi- a microscope and a magnifying viduals in a population and pass on glass, Morgan and his colleagues these inheritable genetic character- confirmed the chromosomal istics to their offspring. Simply put, theory of inheritance: that genes natural selection is a consistent dif- are located on chromosomes like ference in survival and reproduc- beads on a string, and that some tion between different genotypes, genes are linked (meaning they or even different genes, in what we are on the same chromosome and could call reproductive success. [A always inherited together). One of genotype is a group of organisms his students, Alfred Sturtevant, cre- sharing a specific genetic makeup.] ated the first ever genetic map, a landmark event in genetics. BurchGene Magazine | May 2016 History of Genetics 27

1972-1972- First First recom - 6 binantrecombinant DNA DNA The first production of recombi- nant DNA molecules, using restric- tion enzymes, occurred in the early 1970s. Recombinant DNA technol- ogy involves the joining of DNA from different species and subse- quently inserting the hybrid DNA into a host cell, often a bacterium. 1983- PCR Invented 1952-1952-Genes Genes Are MadeAre Made of DNAof DNA 8 The polymerase chain reac- 4 tion (PCR) technique, invented in Alfred Hershey & Martha Chase 1985 by Kary B. Mullis, allowed show that only the DNA of a virus scientists to make millions of needs to enter a bacterium to copies of a scarce sample of DNA. infect it, providing strong support The technique has revolutionized for the idea that genes are made many aspects of current research, of DNA. Alfred Hershey was a including the diagnosis of genetic phage geneticist who, with his defects and the detection of the research assistant, Martha Chase, AIDS virus in human cells. The did one of the most famous exper- technique is also used by crimi- iments in molecular biology. The nologists to link specific persons to “blender” experiment proved that samples of blood or hair via DNA DNA carried genetic information. comparison. PCR also affected evolutionary studies because large quantities of DNA can be manufac- tured from fossils containing but 1975-1975-DNA DNA Sequencing trace amounts. 7Two groups, Frederick Sanger and colleagues, and Alan Maxam and Walter Gilbert, both develop rapid DNA sequencing methods. The Sanger method is most commonly employed in the lab today, with colored dyes used to identify each of the four nucleic acids that make up DNA. In the past, scientists used radioactivity to mark the ends of DNA chains; now, they use colored dyes. 2003-2003- CompletionCompletion of ofthe Human the Genome Human 9 Project 1953- DNA Double Helix The Human Genome Project (HGP) 5In 1953, the race to deter- was one of the great feats of explo- mine how these pieces fit together ration in history - an inward voyage in a three-dimensional structure of discovery rather than an outward was won by James Watson and exploration of the planet or the Francis Crick at the Cavendish cosmos; an international research Laboratory in Cambridge, England. effort to sequence and map all of They showed that alternating the genes - together known as the deoxyribose and phosphate mole- genome - of members of our spe- cules form the twisted uprights of cies, Homo sapiens. Completed in the DNA ladder. The rungs of the April 2003, the HGP gave us the ladder are formed by complemen- ability, for the first time, to read tary pairs of nitrogen bases — A nature’s complete genetic blueprint always paired with T and G always for building a human being. paired with C.

BurchGene Magazine | May 2016 KEEP CALM AND LEARN GENETICS