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Review 8

גיליון 8 – חושים, ינו' 03

על טעם ועל ריח – הבסיס הגנטי, פרופ' דורון לנצט

Prof. Doron Lancet, head of the Center for Human Genome named Crown, Hhmhlkh Genetics Molokolrit, Weizmann Institute of Science, Rehovot

our ancestors were fascinated by the chemical senses – taste and smell. The fact that supra taste and smell do not argue "attributed whim of people seemed to them that there is something mysterious about the way we identify aromas and flavors, and the mystery of these survived until recently . Many theories have abounded in relation to the question of how to operate cells sense the nose and taste buds language, and no one was able to explain the rework satisfactorily.

already in the 19th century it became clear that cells with life body organs are sophisticated chemical recognition mechanisms. It was coined by Emil Fischer, the image of the key and lock the manner in which the protein detects the material attached to it. For example, proteins found in saliva enzyme, amylase, joint uniquely starch in food, but remains completely indifferent to any "key" to another chemical. Unique relationships such recognition also exist regarding the receptors on the cell surface. liver and muscles receptor protein is powered solely by the hormone insulin, secreted by the pancreas gland, and the brain has a different receptor, sensitive to adrenaline, but not for a number of other chemical compounds.

sense the smell also reveals a significant degree of uniqueness. Indeed, this is a sensory facility has a wide spectrum incredibly, since almost all volatile organic clay evokes the smell. But on the other hand, epithelial cells sense of smell nose can distinguish fine gradations, even between optical isomers. Thus, while Aster such as amyl acetate has the aroma of fruit (banana), Lbnzaldhid fragrant almond, and camphor – smell "health" spicy. Isomer right Karjuan smell of caraway, while left mint. One of the pioneers of the study of the sense of smell, John should , claimed to have been in the sixties that these phenomena can be explained, but only via protein receptors equipped with recognition sites that can identify the shape of the scent molecules. He also described seven basic odors represented by receptors with different structures.

but for many years there was widespread opposition's pioneering ideas should. Difficulties arose because the set "relations between structure – function" of its chemical structure of smell and sense of smell it raises. These relations exist, for example, hormone receptors, and they allow understanding Mngnonm, and even design new drugs that target them. Because of these difficulties, many gave up on the idea that protein receptors are the usual fragrant responsible for recognition. Mechanisms of the alternative proposed included punching tiny lipid membrane surrounding the nerve cells in the sensory, separation chromatography of fragrance materials on the surface of the tissue sensory, or even Transmission infrared light by fragrant, so as to create vibrations unique cells sense.

olfactory epithelium cells in any sense able to distinguish fine gradations, even between optical isomers. Thus, while Aster such as amyl acetate has the aroma of fruit (banana), Lbnzaldhid fragrant almond, and camphor – smell "health" spicy

discoveries in genetics olfactory revolution which restored the protein receptors fore bolts occurred due to the development of molecular genetics in the last twenty years. Notably, this was a classical genetics John gave the clearest clues should first operate receptors that latch after all. This scientist was a pioneer in the study of the unique anosmia (Anosmih specific). This is a common phenomenon among people, which is expressed by virtually every person has the ability to sense smell flaw or another. Should show that in every detail the defect occurred on a limited number of fragrant alike, while its absorption capacity other chemicals absolutely normal. Also, should and others have shown, these defects are inherited. The road was so brief to the conclusion that among the genes that determine the structure and functions of the body, there are olfactory receptor gene predictors protein. In such a mutation in a given cause disappearance of the ability to feel a certain smell. But despite efforts not small, left receptors unknown, and no one was able to isolate the protein level or clone the gene predictors them.

It was in 1985 discovered fundamental discoveries first which eventually led to deciphering the mysteries of olfactory receptors. Our laboratory the Weizmann began doctoral student, Umberto Pecha study was based on the following idea: If it is difficult to find the receptors, may be, as a preliminary step, to discover the pathway modeling receptors which form the electrical signals coming from the brain. This event offered an analogy to the functioning of receptors for adrenaline. There was known for many years, the mechanism comprises two key proteins: Protein G amplifier used in biochemical and enzyme Adnilil Tziklz, which produces "secondary messenger" – AMP circuits. Indeed, experiments membranes (membrane) olfactory cells of frog discovered, fragrances such as amyl acetate causes a tremendous increase in production above mentioned secondary messenger. Evidence also emerged G protein sharing mechanism absorbing odors.

Six years later served as the basis of this finding to detect the receptors themselves. This is done by Linda Beck, who worked in the laboratory of Richard Axel of Columbia University in New York. This major discovery that the Haka central role in molecular genetics. Used the idea that each G-protein receptors operators, there are common themes. Using short segments of DNA receptors belong to the G Mfaili- the brain, Dr. Beck was able to "fish" from a library of DNA fragments in the rat dozen sense of smell receptor genes. It turned out quickly that this is a huge family of genes, more than a thousand in number, all one of them is responsible for the absorption of a particular sector of fragrances.

past ten years. in 2001, published in the prestigious scientific Nature entire sheet describing one of the important achievements of mankind since time immemorial. question decoding the almost complete DNA sequence of the human genome. Israel's contribution to this article specified arrival to the complete set of human genes predictors olfactory receptor. That same year deciphered other laboratories around the world the secrets of receptors tastes sweet and Mr, and the taste receptors mono-sodium glutamate, known in Japan as Aomami.

mutation – the key to understanding file Info it opened endless possibilities for understanding the chemical senses. This analogy the general area of the study receptors, there allows a different era-genomic deduced sequence of bases of DNA ciphers specific receptor the structure of the encoded protein. Hence, using chemical methods, and importantly, to design a "guided missile" – ie, new drugs – operate specific the protein in question. this revolution in the pharmaceutical industry is already under way, but it will require imagination and boldness also be applied to the world of the conservative little more of the manufacture of smell and taste. this will probably in the near future to plan flavor and aroma, and a new heaven, based on genomic information to receptors relevant.

but remains more fundamental question: how can we associate with the receptor or two out of a universe of a thousand receptors position sensing of a particular scent? modern genetics decodes the role of normal given gene by studying the mutations that apply to it. for example, mutations are discovered in people who suffer from deafness, indicate the role of a gene that was so far anonymous, in charge of contact between nerve cells in the inner ear and the brain. Is it possible to return to the cases of anosmia unique studied decades ago by John supposed to, and used for the functional identification of some of the hundreds of odor receptors? Obviously, the first condition for this is the discovery of cases, the person or another, has a specific receptor mutation disable it.

Although the search field is not the entire genome, but only a group of all olfactory receptors, conquer The operation for searching needle in a haystack. Is it possible to narrow the search to a subset of genes? Last year found that students in my laboratory research and Idan Yoav Gilad Manasseh possible strategy. To formulate it clearly has an in-depth look at a little more complete collection of olfactory receptor genes, it gleaned painstakingly DNA sequencing and data B"criit "genome databases. Discovered unexpectedly, about two-thirds of these genes were controversial neutralize their ability to encode a protein right . genes Russians such as these are called pseudogenes.

but what use pseudogenes? and, are they destroyed all mankind! genes such do not meet the criteria required, which means that a gene will be deactivated only in the details certain population, and right in all the other people. the question is, then, could it be that some pseudogenes are discovered are polymorphic, meaning that they have more version sequence one? This is the term used by geneticists to mark symptoms such genetic differences exist in the population sensitivity alcoholic beverages or drugs. the strategy that we developed is limited, therefore, that we managed to formulate criteria making it possible to sift Fsoidognim polymorphic among all the rest.

for testing experimental sites of genetic variation in human in question, we used modern technology imported from Israel just this year. This is a method which can test DNA sequence differences in the population using mass spectrograph. The method allows to discover the genetic fingerprint of thousands of people in a few weeks. When activated technology for 200 people from around the world, were discovered over twenty different sites such millstones, and counting. Search it helped even store commercial data genome, it acquired the Weizmann Institute two years ago.

It seems, then, that every person in the human population is characterized by a combination certain genes and pseudogenes olfactory receptor. Thus it is possible, Reuben defective genes among several 1,3,8,12,13,17,19 whereas they 3,5,11,13,15,16,20 Simon corrupted. Every detail is characterized by human, therefore, a kind of "bar-code" gene, the black bars are defective genes. Easy to calculate broke a twenty-code stripes create a million combinations, and it is, therefore, also the minimum number of olfactory voted 'versions "in person.

Studies have shown that this phenomenon was reinforced due to evolution wreaked havoc repertoire of olfactory receptors only three years or millions of years. It can be concluded that among apes find that the number of pseudogenes are much smaller. It seems that this occurred due to the fact that in the human species decreased sense of smell somewhat from grace. Despite this, total loss of sense of smell (even that is explored genetic), is quite a blow, and hence whose importance to man. Such loss is almost completely eliminates the abilityenjoy food and beverage, mistakenly attributed to feel the taste. for creatures such as dog and mouse, their sense of smell developed much more, there are a few more of the genes are turned off, presumably due to there including greater uniformity of information.

It turns out that every person in the human population is characterized by a combination of genes and pseudogenes olfactory receptor. Every detail is characterized by a kind of human "bar-code" gene, the black bars are defective genes. Easy to calculate broke a twenty-code stripes create a million combinations, and it is, therefore, also the minimum number of olfactory voted 'versions "in person

Future applications < / strong> The next step in the long journey in North sense of smell is making a process known as "research associate". This is a method used by research institutions and pharmaceutical companies to detect multi-gene diseases gardens. These diseases, such as hypertension, asthma, diabetes and schizophrenia, are caused by a combination of small changes in many genes. To find out who are the same genes causing the disease of this kind, examining hundreds of genetically different sites, looking for each statistical correlation for the disease. Currently performed in our laboratory research of this kind, in which thousands of people. Aims to find out the correlation between this version or another of the bar-code Smell, and anosmia unique fragrant given.

For many years lagged study of olfactory receptors and taste different research areas other molecular biology. Twenty years have brought the most significant breakthroughs, and these senses name on the map. Today, there are cases in which the study of these senses is used to flag the camp, for example on human variation pseudogenes, or mechanisms for construction of neural networks.

companies, the issue of taste and smell are our main concern business, must learn to take advantage of these important developments. Soon the participants in a panel of human and material testing will taste new genetic test, to examine the extent to which they represent the bar code smell characteristic of the target population. It is also possible the development of personal perfumes, medicines analogy-based personality genes, which describe the next development in the medical field. Thus, with the help of modern genetics innovations, we may go back and argue about taste and smell.