Monday, January 28, 2013

The spread of social phobia persons genetic and environment-related.

The spread of social phobia persons genetic and environment-related.

Genetic determinism: Implications scientific, medical and ethical
 The formulation of the theory of evolution, there are nearly 150 years, advances in genetics for over a century, and the rise of molecular genetics that followed the discovery of DNA there are more 50 years have profoundly changed our vision and understanding of the living world, health and human diseases.
Ambiguity of the notion of genetic determinism
Developments in molecular genetics, genetic engineering, and the draft human genome sequence has facilitated the dissemination of knowledge in society about the relationship between genes and diseases. The identification of genetic sequences involved in many diseases inheritance (Huntington's disease, muscular dystrophy, cystic fibrosis, sickle cell disease, fragile X, colonic polyposis family familial forms of breast cancer ...) or occurred spontaneously ( trisomy 21) has led to a better understanding of the mechanisms responsible for the development of these diseases, diagnostic tests or predictive, and in some cases, therapeutic measures for preventive or curative. The proliferation of GMOs (genetically modified animals or plants by the transformation of a gene, the insertion of an additional gene or otherwise deletion of a gene) and the discovery of some spectacular effects of these changes on certain characteristics of these organizations or their health has reinforced the idea of ​​the importance of genes in living organisms function. There was even enough showing that genetic introduced into a bacterium, or an animal cell, a human gene that allows human cells to produce insulin for the most common bacteria or animal cell produces human insulin.
These findings have not only resulted familiarize society with genetics and raise both hopes and concerns to the increasing development of its applications. They have also helped to strengthen the society of ancient and widespread notions of genetic determinism according to which our identity and our future - what we are and what we will become - are primarily or entirely determined by our genes. In this vision, the destiny of the individual is, from its conception, already registered in the particular sequence of its genes. During the past 20 years, work suggesting that violence, aggression, addiction, fidelity, love, homosexuality, religious faith ... are related to variations in one or several gene (s) specific (s) have experienced significant media coverage and widespread popularity. And it is in this context that are often included expectations regarding the development of a predictive medicine based on genetic testing.
Three distinct issues emerge that can be made in the following manner. The first is: the identity and fate of a person they are already written somewhere, since its conception? It is a question of a metaphysical nature. The second is: the identity and fate of a person they are, in part, read somewhere, and if so, where, how, and to what extent? It is a question of a scientific nature. The third is that the results actually mean that science gives us, and how we can and we want to reconcile with the very values ​​that underpin research, medicine, and more broadly, our society? It is a question of an ethical nature.
If the concept of "any genetic" began to fade from many researchers (Atlan, 1998), it still leads often to ignore or neglect the body of research on the complex interactions between genes and environment - and a more broadly between nature and nurture - heredity and in the emergence of the uniqueness of each person. The exploration of this complexity is the field of study of a field of research in full expansion: epigenetics, which is literally "above" genes, that is to say upstream of genes, that the control, even in a hierarchical way, what could be more important than genes.

Old question of heredity
The emphasis on the question of heredity is probably as old as the history of mankind. Extremely schematic way, we can consider that this issue has been addressed in two very different ways throughout history. The first approach was the order of the questions: what are the respective shares of the innate and acquired - or more broadly the nature and culture - in the emergence of the unique characteristics of a person? What is the role of heredity in this part of innate? And what might be the mechanisms by which hereditary characteristics to transmit, mix, and change from generation to generation? This approach to questioning, the search order is that which modern biology began, 150 years, to provide answers more accurate and often surprising. The second approach has not made an inquiry, but rather an action based on a presupposition. Starting from the notion that the essential characteristics and capabilities of a person could only be a priori related to heredity, it was to ensure that the social role, activities, and capabilities of a person are intimately linked to heredity: it is a social process whose examples are endless - the hereditary monarchies, aristocracies, caste system, arranged marriages ... If we do not take into account the entanglement between the former two approaches - questioning and, on the other hand, a priori answer - it is difficult to understand how modern science has been, and can still sometimes enroll in his questioning assumptions elders in existing responses that can guide and constrain the interpretation of research results.
Two ideas blend into effect today in the belief in a strong genetic determinism or absolute. The ancient idea that the essential characteristics and capabilities of a person, and an essential part of the future are determined by heredity and modern avatar of this idea, that a biological discipline - genetics, science Heredity - alone can account, in a simple and comprehensive, the uniqueness of a person and its future.
It is in the development of research using both the old assumptions and technical innovations more modern than the main risks arise probably drift scientific and ethical part of contemporary research on the genetic determinism of complex diseases, including complex diseases and disabilities affecting behavior and social interaction skills. It is not to prejudge here is that the mere fact that these concepts are old they are a priori devoid of any scientific basis: the exploration of the unknown can, by definition, book all sorts of surprises and the history of science is full of examples of concepts rediscovered the importance of which has long been ignored, denied, or ignored (Lightman and Gingerich, 1992; Ameisen, 2003). But it is important to realize that these old concepts concerning heredity not only a long scientific history: they also had a sometimes tragic history regarding their ethical implications (Gould, 1981 and 2002, Rothstein, 2005 .

Unethical the notion of genetic determinism: Social Darwinism to eugenics ...
The extreme views of genetic determinism have ancient roots. They go back to the theories developed by geneticists and Haldane Fischer during the first half of the twentieth century, and even before the (re) discovery of the gene in 1900, a vision of heredity developed in the late nineteenth century by designers of "social Darwinism" (Gould, 1981). In 1883, twenty-four years after the publication of "From The Origin of Species", and a year after the death of Darwin, Francis Galton created the term "eugenics" to explain how he proposes to the company use the concepts of "scientific" new theory of evolution and natural selection. We must, he writes, "limit excessive fertility of those who failed socially," thus designating the "social failure" as an inherited trait, one of the first modern formulations of the inheritance of behavior, which leads, after (re) discovery of genes, to seek genetic causes (Gould, 1981 and 2002). And is fascinated in finding a form of "natural law" to establish or own to justify the functioning of our societies were born the excesses of "Social Darwinism".
We can not forget had some consequences of these ideas, whose spread was extremely fast and had a profound influence on society in the late nineteenth century and the first half of the twentieth century. For example, the so-called "discovery" of the genetic basis of a lack of intelligence and "antisocial behavior" among immigrants from Europe and South East has led the United States in the early twentieth century, the development of highly restrictive immigration laws with respect to these populations in order to protect the "health" mental and social situation. Genetic basis of the alleged crime, mental health and "antisocial behavior" has also led, in the early twentieth century, the introduction of compulsory sterilization laws favoring, referred to eugenics in many democracies Western Europe, and many states in the United States: Tens of thousands of people were sterilized as well (Gould, 1981 and 2002, Rothstein, 2005). Some of these concepts were the basis, in Nazi Germany, in the development of racial laws, euthanasia of the mentally handicapped, and genocide. And it is in the judgment of Nuremberg, in 1947, what emerged the principles underlying modern bioethics.
The recurrent temptation to discover a grid of one-dimensional - the analysis of the shape of the skull, for example, the anthropology of the early twentieth century, or the gene sequence for modern genetics - which is enough finally to alone to account for different levels of complexity of life and the human, often leads to the evolutionist Stephen Jay Gould called "Mismeasure of Man" (Gould, 1981): Mismeasure a scientific and Mismeasure ethically.
In 1893, Thomas Henry Huxley, who was one of the most ardent defenders of Darwin, suggested in a prescient lecture entitled "Evolution and Ethics" a radical vision of how humanity should use its knowledge of the "laws of nature "in the development of moral values. "We must understand, once and for all," he said, "that the ethical progress of society depends not on its ability to mimic the cosmic laws, let alone to flee, but his ability to fight "(quoted in Dawkins, 2003). However, it is probably not so much to fight than trying to understand. To use our new knowledge as a source of inquiry and reflection, and not as an excuse for desiccate our humanity. And constantly attempt to strengthen the link between changing still fragile and the scientific approach - our question about what we are - and the ethical approach - our question about what we want to become, for us to invent and build the better future in our respect for the otherness of the dignity and freedom of every human being.
Today, more than in other fields of genetics, it is probably genetic diseases that affect behavior, social interactions, and mental abilities, and genetic traits, which pose not only ethical problems, but also problems of scientific understanding (Rothstein, 2005(.

Avatars science the notion of genetic determinism: the modern synthesis selfish gene ...
The mid-twentieth century, the modern synthesis realized the integration of genetics to Darwin's theory of evolution (Gould, 2002; Ridley, 2004). Emerged for the first time a unified conception of biology, whose explanatory power and the implications were of great wealth. These implications were still limited by some of the architects of modern synthesis, and some of their successors, such as Williams and Dawkins, deeply influenced by the ideas of Fisher and Haldane, who believed that evolution was primarily the result of adaptive changes in the frequency of genes in populations, and attributed a quasi-exclusive processes of natural selection operating at the level of genes. Basically, any genetic variation would necessarily be a consequence beneficial or detrimental to the spread of genes and the environment would be a filter, promoting or restricting the spread of organisms inheriting these genetic variations specific. However, this extreme view was challenged even before the emergence of the modern synthesis, by Wright's theories on the importance of "genetic drift" independent of natural selection (Wright, 1932), and later, by the "neutral theory" of evolution proposed by Kimura (1983), and the notions of "exaptation" (multifunctionality) of "multilevel selection", and multiple constraints developed by Gould (2002).
The reductionist view of biology and evolution of the single "point of view of the gene" (where the unit of selection is not so much the body, as Darwin and his early successors, but the genes that have the organization) has solved many complex problems, sometimes difficult to understand in the context of classical Darwinian theory presented in "On the Origin of Species", although the term "sexual selection" thoroughly developed by Darwin his later work, "The Descent of Men, and selection in relation to sex," presents the perspective that can address these problems. This is, for example, the apparently paradoxical spread of genes whose presence has an adverse effect on the longevity of individuals (Williams, 1957), or even the survival of the species, as is the case of phenomena meiotic distortion which can significantly skew the sex ratio, enough to cause the disappearance of all the individuals of one sex (Dawkins, 1976; Ridley, 2004). This is Dawkins who popularized with great talent and a very successful one of the most extreme visions of genetic determinism offering, 30 years ago, the metaphor of the "selfish gene", writing in the book of the same name: "... [genes] are safe inside gigantic robots ... manipulating the world by controlling it remotely. They [genes] are you and me, they created us, body and spirit, and their preservation is the ultimate reason for our existence ... "(Dawkins, 1976).
In a subsequent book, which is probably his most original, "The Extended Phenotype", Dawkins (1982) shows that this vision "in terms of gene" allows us to reconsider in a new way, some of the more complex interactions between different agencies, in particular the interactions between parasites and hosts they colonize. But the dramatic metaphors about the "selfish gene" favored, despite some precautions Dawkins, wide dissemination in society of the simplistic idea that genes have a role not only actors, but also a form of intentionality. This idea reflects the company sometimes vaguely anthropomorphic notions prédarwiniennes project and purpose at work in the evolution of life, and very old notions of vitalism. However, not only the genes have no intentions, but they are not actors: they are, or are not used by the cells that possess them, and each cell can generally from ' same gene, produce, depending on the circumstances, several different proteins by the involvement of mechanisms continue to be increasingly complex than previously thought (Gingeras, 2006).
These are the proteins that are involved in the cells, and their effects depend in particular three-dimensional forms they adopt, which are not only determined by the sequence of the genes from which they are made, but also depend on the nature and activities of other proteins present in the cells with which they interact and in particular the presence and activity of many protein families "chaperones". And these are proteins (the cell made from some of its genes), which are at work in the production of other proteins from other genes ... There are therefore no chain causality and simple way leading from a gene to a protein, a gene to a "function" or higher because of a gene to the individual ... and the reductive notion but popular "genetic program" is a notion deeply ambiguous: "it is a program," wrote 30 years ago Henri Atlan "who needs the product of his reading and scripts to be read and executed ..." (Atlantic, 1979). Literally "program" means "pre-writing". But what is "pre-written" in our genes, if indeed we can use that word, it is not our identity and our future is a set of opportunities and constraints that the update depends continuously in our history and our environment.
Can we reduce the complexity of living metaphor Dawkins, where genes "manipulate the world ..." and "created us body and mind"? The exterior is at least as, and often more than the inside: the environment is at least as much as genes, acquired as much as innate, and in humans and many animal species , culture as much as the nature. Even if one insists, that there is no reason a priori to choose a point of view centered on genes - rather than, for example, cells, or individuals - must be considered in their genes ( s) environment (s). And the notion of environment (s) is a far more complex than the usually perceives.

"This is about" the environment and its multiple levels
For each of our genes that reside in the nucleus of our cells, a first level of environment, it is our 20 000 to 30 000 genes in duplicate, our 40 000 to 60 000 alleles, which surround and we inherited half of our mother and half from our father. But all our 40 000 to 60 000 alleles, and other areas identified as necessary for our cells to make proteins from these alleles is not total about 30% to 35% of our DNA. 65% to 70% DNA remaining represent another level environment for our genes. And the 65% to 70% of the DNA, which have long been wrongly considered "useless", hence the name DNA "trash" are partly used by the cells, influencing the way they use their genes. For all of our DNA, the environment is composed by proteins of our chromosomes that surround it. The environment of each of our 46 chromosomes, it is the entire contents of the nucleus of each of our cells. For each kernel, the environment is constituted by the cytoplasm of the cell in which it resides. In the cytoplasm of each of these cells are present and reproduce the mitochondria, tiny cells within our cells, which produce energy from oxygen: each of these mitochondria, we inherit mainly our mother (the mitochondria present in the egg) contains a small number of genes different from our chromosomal genes. Each of our cells, genetically identical, belongs to one of the 200 families of our body cells, each differing by their composition, their structure, their characteristics and properties. And for each of these cells, the environment is composed by the tens of trillions of other cells that compose us. And for each of us, the environment, are the other people around us and the diversity of lifestyles, cultures that affect this environment and create new environments are animals and plants, and are germs, viruses, bacteria, and parasites that surround us where we live, and that change constantly. And for all living beings, another level still, the environment consists of the non-living environment - landforms, oceans, rivers, and soil composition of the atmosphere, climate, temperature ... - that living beings themselves, and in particular humans, constantly transforming ...
Of course, a number of basic features (our blood groups, our tissue groups, for example) are directly related to the sequence of some of our genes. But this does not mean that our genes determine our destiny, or more so, they "manipulate the world." There are genes and a variety of environments, including levels interpenetrate and influence each other. In the words of geneticist Richard Lewontin (2000): "The inside and outside of a living being interpenetrate" and the individual can be considered both as a place, object, product, and actor interactions. Development and operating procedures of living imply causality multidirectional, with feedback effects, amplification or inhibition at different levels of organization: networks of proteins, cells, networks of cells, organs, systems organs, individuals, networks of individuals, species networks, networks of ecological interactions ... And at these levels, which emerge various forms of interaction and organization, most elements are found in the words Pascal, "things at once and caused causantes." And more so that the characteristics we analyze the result of the integration of a large number of different levels of interaction, as is the case, for example, behavior.
The notion of "all genetics" - the notion that the human person can be reduced to a single genome - began to fade in the world of biomedical research. But it nevertheless continues to be prevalent in society, and even among many researchers and doctors, as witnessed debates on "reproductive cloning", and in particular the terms and concepts of "double" and "copy" , for people who, like identical twins, share the same genome. Awareness, in 2003, the human genome did not, contrary to what had been announced some of its proponents, "reveal human nature" or to understand and treat our illnesses, played a role in the review of these notions of absolute genetic determinism. The discovery that we have no more genes than the mouse, not much more than the fruit fly, and much less than rice, suggesting that the relationship between our genes and our identity is not limited to a simple relationship linear causality between a "gene" and "function." Regardless of the question of numbers, these studies also revealed that our genes shared many similar sequences with genes of the mouse and the fruit fly ... The sequencing in 2005 of the chimpanzee genome, confirming that we share more than 98% of the sequence of our genes, not allowed to reveal to his reading, the nature of genes or gene sequences that were the specificity of our "human nature", compared with "nature" our non-human kin (Chimpanzee Sequencing and Analysis Consortium, 2005). In other words, we know that there is a link between genes and the development, survival, and behavior characteristics of living beings: the issue is the nature of this relationship is that, in most cases, far from simple, unidirectional, rigid and usually we tend to imagine.
In this issue of the relationship between the genome and the characteristics of a living species is superimposed another, that variability even within a species alive. Is there a human genome "normal"? And if so, what its characteristics? And that may well mean the term "normal" in the context of the evolution of life and the continuous mixing of individual variation produced by sexual reproduction?

Gene concept "normal" gene "abnormal" or "transferred"
Most often, the notion of characteristic "normal" or "abnormal" for an individual, appears at first obvious. However, it is a fuzzy concept. It is indeed primarily a statistical concept, a difference of variation in these characteristics compared to a hypothetical individual who does not match any particular individual, but to an average of individuals belonging to the same species. And the statistical concept appears to prejudge a priori a profit of "adaptive advantage" it is "normal" and therefore "good" for a bird to have wings and can fly, it is "normal" and therefore beneficial to a mammal having no wings, and therefore not able to fly ... But it can also be "normal" and "good" for a mammal to have wings and can fly, as This is the case of the bat and a bird have wings and can not fly, as is the case of the ostrich ... In this context, the concept of gene "normal" or " abnormal ", although widespread, is also deeply ambiguous.
When we try to go in search of the origins of the human genome "normal", this journey takes us back through 4 to 6 million years, until our last non-human primate ancestors we share with chimpanzees. And recent genetic studies suggest that interfertility later period between our first human ancestors and forefathers chimpanzees may have occurred, altering the first human genome in the process of differentiation (Patterson et al., 2006 ). Paleontology also teaches us that we are only one human species to which these ancestors gave birth, the only one not to have disappeared. The essence of "human nature," the "standard human" is lost in our genealogy: the first human beings "normal" were, in an apparent paradox, non-human primates "abnormal".
The genes are in germ cells that give rise to eggs and sperm, various modifications (mutations, insertions, deletions, duplications ...) that can then be transmitted from generation to generation, and that sexual reproduction breaststroke continuously mixtures and diversity. And these genetic variations accumulate and spread over time that there are, at any given time, for each gene, several different forms (alleles) whose distribution in the human species differed and differs Today, according to history and place (space and time).
Consider, for example, the color of the skin, a feature whose genetic bases are just beginning to be explored (Lamason et al., 2005). We do not know the (or) color (s) of original skin (s) "normal" human beings first. Today, skin tone, rare in one place may be common in another place, or have been common elsewhere at another time. The color of the skin is not only a source of diversity, but can also be a source of disease depending on the environment in the tropics pale skin favors the development of cancers of the skin, dark skin in the northern hemisphere favors the development of rickets in children and requires prevention by dietary vitamin D. But the color of the skin can also be a source of disease due to causal loops much more complex: not only in terms of the climatic environment, but also the human environment. The behavior of others, discrimination, by living conditions that can cause, or the restriction of access to care, may be a source of diseases whose transmission tree can give the illusion of a cause inherited, a genetic cause (Duster, 2005(.

Genetic variability and health
The notion of "normality" is often associated with the concept of health. However, the World Health Organization (WHO) defines health not in reference to a "standard" anyone but "a state of complete physical, mental and social" is not the healthy person "normal", but the person who feels good. The relationship between genes and human health should not arise a priori in terms of allele "normal" or "abnormal", frequent or rare, but in terms of alleles favoring or not the likelihood of suffering taking into account the complexity of causal links that may come into play in this area, in particular those related to the environment. And our vision alleles that favor the likelihood of suffering - the likelihood of disease - is usually quite brief. We want to know what are the alleles that would be desirable to be healthy and what are the alleles that would be undesirable in terms of health. This question, posed in these terms, probably did not make sense with regard to the vast majority of our alleles, and the vast majority of diseases. But for a large number of diseases, most often rare, it has medical implications essential.

Monogenic hereditary diseases with Mendelian inheritance and high penetrance: an allele / disease
The notion of genetic determinism is particularly strong due to the discovery of hereditary diseases that are caused by the transmission of a particular form of a single allele (single or duplicate, as appropriate) and for which, If the presence of this allele (or both alleles) in the genome, the likelihood of the disease (called penetrance) is strong. These monogenic diseases are numerous, but most rate rare, severely debilitating and often fatal in the absence of effective treatment and prevention: Huntington's disease, muscular dystrophy, amyotrophic lateral sclerosis, phenylketonuria, hemophilia , cystic fibrosis, hemochromatosis ... (Kasper et al., 2004).
In these monogenic diseases, the allele (or both alleles) in question is (or are) Legacy (s) under the laws of genetics described there are more than a century by Mendel. What is it? We have about 20 000 to 30 000 genes, each in duplicate, in most cases, two different alleles for the same gene, located on our 22 pairs of non-sex chromosomes, and double or single copy on our two chromosomes sex, as they are symmetrical (XX in females) or asymmetric (XY in humans). Monogenic diseases are called Mendelian transmission when only the dominant presence of one particular allele for the disease develops: the probability, when one parent has the allele to transmit this allele to one of its children is 50%. Monogenic diseases are called Mendelian transmission takes two recessive alleles when individuals of the same gene are present for the disease to develop: in the presence of one of these alleles, there is often not disease (and in any case not as serious illness), the other allele, "ordinary", while being sufficient to prevent the onset of disease. In case of a recessive disease, the probability when each parent has one allele having a child that has both alleles and risk of developing the disease is 25%. When a recessive allele is present on the X sex chromosome, the disease occurs more frequently in men, since man does not have a second X chromosome that may contain the allele corresponding "ordinary". A woman who has two X chromosomes (one X being used in each cell, but not the same as cells), no risk, where disease is recessive to develop the disease if it has two alleles associated with disease.
Finally, some monogenic hereditary diseases are caused by variations in mitochondrial genes: they are then transmitted by the mother, with probabilities that do not correspond to the laws of Mendel (who studied the transmission of characteristics related to chromosomal genes).
Dominant hereditary disease, fatal or severely debilitating in the absence of effective medical treatment, and that the likelihood is very high (high penetrance) occur generally after the age of reproduction: in fact, if a disease resulted in death or significant disability before puberty allele could not be passed from generation to generation. One example is Huntington's disease, fatal neurodegenerative disease, including age of onset is variable, but generally after 40 years (Kasper et al., 2004).
However, some recessively inherited diseases can be fatal or severely debilitating early childhood, without having prevented the transmission of these alleles through time, to the extent the transmission of a single copy of the allele s accompanying or any disease, or a very mild form of disease compatible with survival and reproduction in the absence of any treatment. Cystic fibrosis is an example of this type of hereditary monogenic Mendelian recessive theoretical frequency in the general population, individuals inheriting one of more than a thousand different alleles (whose presence in duplicate promotes the development of cystic fibrosis ), and do not develop disease in France is about 1/30. Thus, in the general population, the theoretical frequency of children at risk of developing the disease, and who were born to two parents with each of these alleles is 1/30x1/30x1/4, that is to say 1 / 3600 (the introduction in recent years of neonatal screening for the disease in our country showed that the actual rate was a bit lower).
The identification and study for over 25 years, thousands of alleles involved in monogenic diseases have high penetrance revolutionized the understanding of the mechanisms involved in these diseases, and helped develop diagnostic tests or screening to develop in some cases preventive or curative treatments and to better understand the functioning of the body and hence, various other diseases (Kasper et al., 2004; Munnich, 2005). At the same time, the fact that in many cases of Mendelian diseases and high penetrance, the presence of one or two particular alleles is frequently accompanied - or very frequently - the development of the disease has greatly contributed to the notion of absolute genetic determinism.
But we actually learn Mendelian inherited diseases with respect, in general, the genetic determinism of disease?

Read the future in the genes? A metaphor for the risks of overinterpretation
Mendelian inherited diseases in high penetrance, the mere presence of a particular allele (dominant diseases) or two particular alleles (recessive diseases) of the same gene, the 20 000 to 30 000 alleles that we have in duplicate (40 000 to 60 000 alleles, say approximately 50 000) is sufficient to predict with high probability the occurrence of a disease. In other words, if the particular sequence of only 2 per 100 000 (50 000 on one allele for a dominant disease) to 4 per 100 000 (50 000 on both alleles for a recessive disease) of all our genes is sufficient to predict with a high probability of occurrence of a disease, it means he that the predictive power of our genes is huge?
The problem is that predicting the likely occurrence of a fatal or debilitating disease from the particular sequence of alleles of a given gene does not necessarily imply that one can read the future in the genes.
Insofar as the belief in an absolute genetic determinism derives part of its fascination from some form of vision that tends to dehumanize, mechanize, and reify the human person, it may be useful to explore the possibility of overinterpretation of such an approach, to use a metaphor for a moment mechanics. It is not of course compare a human being to a machine, but rather to try to understand how a process which aims to predict the future of life and human assimilating in part to a machine (a mechanical genetics) may, in the context in which it takes place, leading to illusions about its predictive capabilities.
Therefore consider an example - schematic caricature and metaphorical - prediction on a machine. When the space shuttle Columbia exploded after takeoff in 1986, killing the entire crew, and a teacher she carried on board, a commission of inquiry of the Congress of the United States tried to understand how such a catastrophe could occur. The physicist Richard Feynman, known both for the importance of his work, which had been awarded a Nobel Prize for its great originality and was part of this inquiry: it caused a big surprise by showing that the cause of the explosion was due to a lack of deformability of certain joints of the shuttle in response to sudden changes in temperature. He demonstrated by soaking in front of the television cameras, one of these joints in a glass of cold water. Thus, a joint that had a defect deformability could predict with a very high probability (certainty?) As the space shuttle, made tens of thousands of different components, explode in response to changes in temperature that would follow his little takeoff.
Did it mean that the study of seals or other components of a space shuttle can, in general, predict the duration, direction, travel destination ... a space shuttle? No, of course. But the study of a particular component, if it reveals the existence of a constraint, will make a prediction very safe, because it is a constraint that will jeopardize the integrity of all. The study of the components of a space shuttle does not in itself predict the future, except in cases where a particular component has a very high probability of causing a disaster.
In other words, the universe and leaving to return to living mechanical and human, a simple concept, yet rarely seen, is the following: the fact that specific sequences, called "abnormal" a number of alleles predict, in many cases, the occurrence very likely a very debilitating disease or death does not mean that the sequence of any allele, in general, allows to predict the future in terms of health and disease. The sequence of specific genes may have predictive power, more or less, in probabilistic terms, in the development of a disease. But, apart from these cases, the analysis of gene sequence, can not - in any case can not now, in the current state of knowledge - to predict the future of a person.

Genetic abnormalities "silent" or "talking" and external environment
Even in cases where a particular sequence, called "abnormal", an allele according to Mendelian heritable, is associated with a very high probability to the occurrence of a particular consequence on health, it should be borne in mind two important concepts.
First, when the disease does not declare at anyone with the allele (or both alleles) involved when penetrance is strong but not total, which is most often the case, genetic testing does not predict the Future of the person: it predicts a probability, more or less, of the occurrence of the disease. What are the factors that modulate the penetrance? It may be the nature of the allele, or environmental effects: effects of the internal environment, genetics, due to the presence of other alleles, corresponding to other genes, or effects from the external environment.
The second important concept is that, in some cases, the probability of occurrence can fully depend on the nature of the external environment with which the child or the person will be in contact: in a given environment, the probability is very high and in another environment, it may become zero.

Example of phenyl ketonuria
In many monogenic hereditary diseases and Mendelian transmission high penetrance (Huntington's disease, amyotrophic lateral sclerosis, muscular dystrophy ...), in the present state of knowledge, the presence of one or two allele (s) particular ( s) of a gene is correlated with a high probability of developing the disease regardless of the environment in which the person will live after birth. But in some of these diseases Monogenic Mendelian penetrance strong presence of the allele in question does not necessarily predict the future regardless of the environment. One example is a recessive disease phenylketonuria. The presence of two particular alleles of the same gene causes inability to properly convert an enzyme one of the amino acids present in the food, phenylalanine, tyrosine, leading to accumulation of toxic compounds in the brain, and significant mental retardation in childhood (Kasper et al., 2004; Munnich, 2005). Routine screening at birth (not by a genetic test, but a test that demonstrates the operation of the corresponding enzyme) has 30 years to save all the children who inherited these alleles implementation from birth with a simple diet low in phenylalanine and tyrosine enriched.
Thus, even when the probability of occurrence of a disease monogenic Mendelian transmission is extremely strong in a normal environment, "normal", a change of this environment can make this probability zero. When there is no change in the familiar environment that allows to prevent the disease from developing, fate is entirely dictated from within by certain genes (but even in these cases, there may be questions about character seemingly unstoppable, see below).

Example of deletion CCR5-D32 and AIDS
There are some rare allelic variations (some "anomalies" genetic) transmission and penetrance Mendelian strong the effect is not to promote the development of a disease, but rather to protect against disease. One of the most dramatic examples is a variation consisting of a partial deletion - deletion CCR5-Δ32 - 32 bp of the promoter (regulatory region) of the CCR5 gene allowing cells to produce the CCR5 receptor. CCR5 protein is a receptor for chemokines, molecules secreted by other cells which cells expressing this receptor to move in the direction of the source of secretion of these chemokines, that is to say, in general , to the site of inflammation. CCR5-Δ32 deletion results in an inability of cells expressing the receptor on their surface (Murphy, 2001; Kasper et al., 2004). Approximately 1% of people from the northern hemisphere inherit two copies of this allele "abnormal" or "defective". These people have no health disorder detectable, but have an important advantage: they are protected, in almost all cases against infection by HIV (Murphy, 2001; Kasper et al., 2004). Indeed, HIV, the AIDS virus uses the CCR5 receptor to enter cells and infect them. In other words, the absence of such an "anomaly" genetic (characterized by the presence of two alleles "abnormal" in the same gene) results for 99% of the northern hemisphere, and almost all of those other parts of the world (where the "anomaly" is virtually absent) to expose the infection by the AIDS virus.
Approximately 10% of people from the northern hemisphere have a single copy of this allele "abnormal", the other being a common form, "ordinary". These people are not little or protected against infection by HIV, the allele "ordinary" for the production of a sufficient amount of CCR5 for HIV that can infect them. But the progression of infection to disease is slowed (Murphy, 2001; Kasper et al., 2004). In other words, the absence of such an "anomaly" genetic result, 90% of people in the northern hemisphere, and almost all the people from other parts of the globe, exposing people infected with HIV at a more rapid development of AIDS.
This "anomaly" monogenic "protective" is transmitted as Mendelian recessive manner with high penetrance. It is a mirror image of monogenic recessive Mendelian transmission and high penetrance that we discussed earlier. But again, let there be no mistake: this form of genetic determinism, which is closely related to the nature of the external environment, is of the order of a particular constraint, allowing the prediction, not a disaster like monogenic Mendelian penetrance strong, but rather a resistance to a particular disaster.
Be "abnormal" does not necessarily mean being exposed to a disease to be "abnormal" can also mean being more resistant than most others to illness.

Variation of genetic sequences, outdoor environments, and diversity implications
The correlations between the presence of certain "anomalies" Mendelian genetic transmission and the probability in a particular environment, develop a disease or otherwise to be protected are not always unidirectional suggest that the examples come from be discussed.

Example of sickle cell anemia and malaria
In 1949, Haldane suggested that the high frequency in a given population, a particular allele increases the likelihood of developing a disease, may be related to another effect, protector of the same allele in some environments.
There are particular alleles which promote the development of severe recessive diseases when they are present in duplicate and, when present as a single copy, promote the development of a moderate form of the same disease, but also the protection against other diseases, death related to the environment. An example is sickle cell disease (Kasper et al., 2004). The allele "abnormal" in question results in the production by the cells form a "abnormal" hemoglobin structure which causes deformation of red blood cells, causing obstruction of blood vessels. When this allele is present in duplicate disorders vessel blockage, and blood clotting disorders that follow can be considerable. When this allele is present in a single copy, disorders are moderated. People with one copy of the allele "abnormal" are very numerous in the population of regions of West Africa where malaria is prevalent: they are generally protected against serious, fatal malaria, which kills Each year more than one million children. Encouraging, despite the health problems it can cause, the survival of those who inherit the frequency of this allele in these populations is most likely due to the protective effect (Kasper et al., 2004).
In an environment where there is no malaria, as the United States, the frequent presence of an allele "abnormal" in the African-American descendants of the inhabitants of these regions of West Africa, which had been deported to the United States by the slave trade, leads to health problems: the "anomaly" genetic "disease." For people who continue to live in these parts of Africa infested by malaria, this "anomaly" protects against a deadly disease common. The presence of this allele is either purely pathological or survival benefit as a function of the external environment. The allele, as such, is neither "good" nor "bad." It depends on the environment, and modern means that we have to protect themselves against malaria.
It is possible that some "anomalies" gene which we see today in the current environment, that adverse consequences in terms of hereditary monogenic Mendelian transmission, have in the past been able to confer benefits in terms of survival or even health. An example might be alleles whose presence promotes the development of hemochromatosis, a disease characterized by excessive accumulation of iron in the body from the diet. Indeed, it is likely that in an environment where food was low in iron, this storage capacity could be a significant benefit in terms of survival and health (Brosius and Kreitman, 2000).

Protection or susceptibility to infectious diseases: back to CCR5-Δ32 deletion
Scarcity, in a population of a particular allele increases the likelihood of protection against a deadly disease in a given environment could be linked to the likelihood of developing another deadly disease in the same environment? CCR5-Δ32 deletion, which protects against AIDS, and that seems to cause any health problems in the northern hemisphere, where it is relatively common, expose it to other diseases in other environments, such as those regions of the southern hemisphere, where the deletion is virtually absent? Works which have been published suggest: people who have two copies of the CCR5-Δ32 allele and are therefore protected against infection with HIV may be more at risk of developing a fatal encephalitis when infection by a flavivirus transmitted by mosquitoes, West Nile virus (Glass et al., 2006). This "anomaly" monogenic which is transmitted as Mendelian recessive manner with high penetrance, does not, unlike, for example, sickle cell anemia, cause health problems by itself. But depending on the microbial environment, it faces a probability of protection against disaster, or could, on the contrary, exhibit a probability of catastrophe. Again, the allele, as such, is neither "good" nor "bad." It depends on the particular nature of the environment.
These concepts have potentially important therapeutic implications. Indeed, some therapeutic strategies currently being explored to prevent infection by HIV, or hinder the development of AIDS are based on the use of drugs to mimic the effects of CCR5-Δ32 deletion, blocking the receptor CCR5 (Crabb, 2006). If confirmed that such interventions may promote the development of deadly diseases in case of infection by flaviviruses, the question of the environment in which the person lives become an essential element in the risk / benefit ratio of such treatment for preventive or curative (Glass et al., 2006; Crabb, 2006). Thus, it may be unrealistic to decide a priori whether a drug, as well as allele is "good" or "bad" if we do not take into account the environment, or if you do unknown effects.

Example of HLA polymorphism
There is an example where this is the same frequency in a human population of an allele, regardless of its particular sequence, which could be an advantage or a disadvantage in terms of health, for the person who inherits it. This example concerns the alleles that cells use to produce the HLA molecules, which constitute the major histocompatibility complex. In this example, it is the scarcity, the character "abnormal", the allele that confers a benefit, and its widespread nature, its "normal", which would present a disadvantage. HLA molecules play an important role in terms of immune response to microbes, and thus in our defenses against microbes. There is a very large HLA polymorphism - very many different alleles - in humans, unrelated individual having a combination of alleles, and HLA molecules, which is clean, explaining transplant rejection almost constant in the absence of immunosuppressive therapy, between unrelated persons (Kasper et al., 2004; Janaway, 2004).
This great polymorphism means that in a given population, exposed to the same germs, most people respond differently (using different HLA) to the same microbe, the more likely it is that a proportion of people possess, by random defense mechanisms that allow them to survive particularly serious infections. But microbes evolve and change continuously from generation to generation, on very short time scales. Studies suggest that people with at a given moment, rare forms of HLA are often better protected, not because these rare forms allow a more effective defense but simply because most of the germs that breed in the majority of the population are not appropriate (Hunter, 2005). If these individuals with rare HLA alleles, but not particularly efficient, have a significant advantage in terms of survival, the frequency of these alleles in the population will gradually increase. Beyond a certain threshold frequency in the population, these alleles will suddenly lose their protective value: no longer rare, and not particularly effective, microbes have adapted. Other alleles become rare, will in turn provide protection against infections ...
This is an interesting example where the rarity alone could have a beneficial effect on survival and health. It is also an interesting example of the risks that may be interpreted too narrowly and too fast the significance of such a correlation between the sequence of a particular gene and the occurrence of diseases. Indeed, if we analyze this correlation at a given time in a given population, between HLA alleles and susceptibility or resistance to infectious diseases, one might be tempted to assign a priori value inherently "pathological" or conversely "protective" in the sequence of certain alleles, whereas the development of the disease or the protection only depends on its frequency in this population. A person who has some of these alleles, "protective" because few, emigrated in a region where these alleles are common, and suddenly lose the protection against infectious diseases they give it. The concepts of correlation and causation are easy to confuse genetics, as in other fields of biology.

Beyond changes in the sequence of genes: genome structure, epistatic interactions and DNA "trash"
The major source of genetic diversity - genetic polymorphism - in humans is the occurrence and spread in the germ cells (the cells that produce eggs and sperm) of inheritable mutations are the most common point mutations, a single base pair of DNA, SNPs (Single Nucleotide Polymorphisms) (The International Consortium Hapmap, 2003, Hinds et al., 2005). Other sources of diversity are insertions of additional sequences in a gene, the deletion of a portion of the gene, or changes not in the sequence of a gene, but the genome structure (Sharp et al. , 2005; Conrad et al., 2006; Gingeras, 2006): for example, a polymorphism for deletions of regions containing genes or not (Conrad et al., 2006) or otherwise duplication of regions containing one or more genes (s) (Sharp et al., 2005), can lead to 1, 2, 3 ... copies of the same gene.

Effect of changes in the number of copies of a gene
An example of this type of polymorphism by duplication of a segment of chromosome, and its consequences for health and disease, has recently been provided by the study of CCL3L1 gene that is used by cells to produce a chemokine MIP -1, which binds to the CCR5 receptor (Gonzalez et al., 2005). This study indicates that people who have multiple copies of the gene CCL3L1 are firstly less susceptible to HIV infection in a population, that people with a low number of copies, and secondly, that among adults infected with HIV in a population, people who have multiple copies of the CCL3L1 gene evolve more slowly to AIDS (Gonzalez et al., 2005). A greater number of copies of the gene allows cells to produce a larger quantity of the chemokine MIP-1, most likely from competing with HIV for binding to CCR5, we saw that it was necessary to HIV so they can infect cells.

Epistatic interactions: effect of changes in the sequence of a gene in response to changes in the sequence of other genes
Among many polymorphisms that influence the operating procedures of the immune system, there is the great polymorphism of alleles encoding HLA polymorphism and smaller alleles encoding a receptor (KIR) that allow some cells killer immune system (cells "natural killer") to kill cancer cells and cells infected by viruses. Studies have been conducted in people infected with HIV to explore the possibility that certain HLA alleles and / or certain KIR alleles can be correlated with the rapid development of AIDS. The presence in a person infected with HIV, a particular HLA (HLA-BW4 B-80I) has in itself no consequence in regard to the rapid development of AIDS, when comparing this person to all people infected with HIV in a given population. The presence of a particular allele KIR (KIR-3DS1) is, however, correlated with a faster progression to AIDS. But in people with both HLA-B BW4-80I allele and KIR-3DS1, progression to AIDS is significantly slowed (Martin et al., 2002).
Thus, the association of an allele with the isolated presence has predictive value zero and one allele whose presence isolated predicts a probability of a poor outcome as a result of a probability predict favorable evolution. In other words, in this case, and probably in many others, the predictive power can have the particular sequence of a given allele depends not only on the nature of the external environment in which a person is immersed : it also depends on the nature of the internal environment of the alleles, and the sequence of other genes, and, in a broader sense, the DNA around them.

Beyond genes: DNA "trash", microRNA ...
Approximately 95% of our DNA does not contain genes, in the strict sense of the term, that is to say, does not contain sequences used by cells to make proteins. Among these DNA regions, some are located within the same gene (introns), others have been identified as long regulatory regions schematically forms of switches, called promoters (Gingeras, 2006). Fixing certain proteins - transcription factors - these promoters, regulatory regions and additional modulates the accessibility of genes to enzymes that initiate the production from these genes, messenger RNA which will leave the nucleus of the cell and allow, in the cytoplasm, the manufacture of the proteins corresponding to the sequence of these genes. Introns and regulatory regions make up about 30% of the DNA. But the rest of the DNA, that is to say about 65% to 70% of the DNA has long been considered "useless", and for this reason, called DNA "trash." However, since about 5 years it became apparent that some regions of the DNA "trash" are used by the cells. It seems that about 10% of this DNA (probably a larger portion of the DNA that constitutes the genes) allows cells to manufacture micro-RNA, including antisense RNA, which will not lead to the production of proteins but can destroy or modulate the stability of certain mRNAs and thus prevent or modify the production of proteins from genes (Mello and Conte, 2004; Claverie, 2005). And it seems that there are about 10 times more of these DNA sequences that are used by cells to manufacture these regulatory RNAs that there are genes (Mattick, 2005).
Thus, knowing the sequence of a particular gene or genes is not sufficient to predict whether - when or at what rate - will be used by a particular cell, let alone the whole body, if we do not know the regulatory sequences of DNA "trash" may modulate its expression, whose exploration has just begun.

From genetics to epigenetics: effects of the environment on gene expression
The most common serious diseases in the rich countries of the northern hemisphere, and in these countries are the main cause of death and disability are heart disease, cancer, metabolic diseases such as diabetes, neurodegenerative diseases ... For some of these diseases, such as breast cancer or colon cancer, or Alzheimer's disease (Price and Sisodia, 1998), in a small minority of patients, the disease is linked to particular alleles, and Mendelian transmission high penetrance. But in the vast majority of people, these alleles are absent: it is not, in these cases, inherited in Mendelian and high penetrance. But the links between diseases and gene sequence is not limited to hereditary diseases: cancers represent a dramatic example of the consequences that may have occurred in a person of some genetic changes in somatic cells.
In most cases, the development of serious diseases most frequent in our country is strongly influenced by environment and lifestyle. The exterior has more often than the interior: the environment and the lifestyle that heredity genetics, acquired more than innate. The environment is not just a filter: it has effects on the body that changes the way the body uses the genes inherited.

Epigenetic memory
The accessibility of a gene in a cell - that a cell is capable or not use it to make proteins - rests largely on the presence or absence of chemical modifications of the regulatory sequences of this gene and changes chemical proteins of chromosomes (histones) surrounding DNA. Enzymatic reactions which cause methylation of regulatory sequences of DNA, and enzymatic reactions that cause, for example, a histone deacetylation prevent the cell to utilize the corresponding gene (Mager and Bartolomei, 2005; Qiu, 2006; Richards , 2006). These enzymatic reactions depend on the particular history of the cell and are influenced by their environment: their differential regulation makes a liver cell does not produce the same proteins that cell of the heart, when they are genetically identical. And it is a form of persistence, memory footprint, these particular usage of its genes, a cell has initiated in response to its environment, which means that, most often, a cell liver remains a liver cell, and give birth to a liver cell. This phenomenon of enzymatic modification of DNA or chromatin that explains how the first cells initially similar that arise from the fertilized egg cell - embryonic stem cells - are gradually transformed into more than 200 different families of cells up our bodies (Mager and Bartolomei, 2005; Qiu, 2006; Richards, 2006). This is also what explains this phenomenon called parental imprinting, the fact that some alleles will not be used the same way by the cells as they were transmitted by the father or the mother (Mager and Bartolomei, 2005; Robertson, 2005; Qiu, 2006; Richards, 2006), he also explains that for women, one of the two X chromosomes is randomly inactivated in each cell (Mager and Bartolomei, 2005 , Robertson, 2005; Qiu, 2006; Richards, 2006). This phenomenon also explains how the transfer of a nucleus (that is to say the set of chromosomes, DNA and genes it contains) a skin cell into an egg whose nucleus has been removed (this is called "cloning") enables the development of an embryo, while in the environment of the skin cell, this kernel only participate in the production of skin cells; an egg does not use its genes in the same manner as a skin cell. But these enzymatic reactions that control the accessibility of genes can be modulated by the external environment, which may alter the activity of body cells (Meaney, 2001; Robertson, 2005; Qiu, 2006; Richards, 2006). And recent studies indicate that two genetically identical (identical twins) gradually acquire, during their lives, epigenetic modifications that lead to different ways of using the same genes, thus contributing to the construction of their singularity, and can be involved in mismatches risk of developing certain diseases which affect one twin and not the other (Otto et al., 2005).
It is the exploration of all the effects of indoor and outdoor environments on how to use genes from the cells, and the heritability of these changes, in the absence of any change in the sequence of the DNA through generations of cells, within an individual, and in some cases, through generations of individuals, which is the field of study of epigenetics (Meaney, 2001; Qiu, 2006 ). Cells are particularly sensitive to these environmental changes during the development of the embryo, and the period after birth. But these effects related to the environment can occur throughout life. The external environment influences the environment within the body, which in turn can affect the accessibility of certain genes or not. Know that allele is present, and know its sequence does not prejudge whether or not to use cells, and therefore the consequences of its presence.
These epigenetic changes, which are very different mechanisms are involved in the development of many diseases (Dennis, 2003; Egger et al., 2004; Robertson, 2005; Qiu, 2006; Richards, 2006) including, for example cancers where epigenetic and genetic changes in somatic cells both play a significant role (Klein, 2005; Feinberg et al., 2006).
But in the context of epigenetic effects of the external environment, the most surprising results are perhaps not affect the development of both diseases, the emergence of some basic physiological characteristics of organisms, such as how embryonic development, maximum longevity and aging, and what might be called behavioral traits, such as the measurable degree of anxiety and memory capabilities measurable. These studies were conducted in animal models, and we do not know, now, how or to what extent their results have implications regarding the human being.

Epigenetics and plasticity of embryonic development
The best known example, the most extreme and long considered an exception for embryonic development in species far removed from ours, such as bees. Two egg cells genetically identical bee can, depending on their external environment (nature of pheromones emitted by queens, or nature of the food supplied by the workers) develop in two different ways which give rise either to small workers sterile, who live two months, either of the queens of large, fertile, who live more than ten years. These dramatic differences, including longevity "natural" order of a factor of 60, resulting from different methods of body building, themselves linked to a differential use of identical genes in that construction.

Epigenetics, aging and longevity
Past ten years, a series of studies has revealed, in some species, the boundaries of longevity "natural" maximum were not as rigid as once believed. In very different animal species, including the last common ancestors back to a period there are about 700 million years - the little transparent worm Caenorhabditis elegans, the fruit fly Drosophila and the mouse - longevity "natural" maximum individuals can be increased by at least 30%, and the onset of aging and diseases of aging much delayed by at least two major types of approaches (Guarente and Picard, 2005; Kenyon, 2005; Kirkwood 2005 Kurosu et al., 2005). The first approach is to artificially produce mutations in a particular gene - to produce new alleles "abnormal" - or delete an allele "normal", or otherwise increase "abnormally" the number of copies of an allele "normal ". The second approach is to modify the external environment - for example, a restriction of calorie rich food. The simultaneous implementation of these two approaches provides, in most cases, no additional gain in longevity, suggesting that they exert their effects on the same process. Thus, a different gene ("abnormal") in a normal ("normal"), or genome normal ("normal") in a different environment ("abnormal") may have the same effect: delay aging (and diseases that accompany aging), thus increasing the longevity of an animal that stays young longer. Change the interior or exterior can have the same effects.

When the notion of genetic inheritance may be a delusion
There are several mechanisms of very different nature, which may lead to an "inheritance" - a stable transmission, do not follow Mendel's laws, through generations of descendants - some individual characteristics, origin epigenetic regardless of any changes in the gene sequence.

Internal environment and epigenetic inheritance
One of these mechanisms is directly related to the transmission of genes: it is the intergenerational transmission of certain terms of epigenetic modifications of DNA and / or chromatin that accompanies the transmission of genes by through germ cells, sperm or eggs, which may, for example variations in terms of parental imprints (Robertson, 2005; Schubeler and Elgin, 2005; Richards, 2006). Another mechanism, long known as common in plants, has been identified for the first time in 2006 in a mammal, the mouse. This mechanism shared with the genetic inheritance that the intergenerational transmission is through germ cells, sperm or eggs (Rassoulzadegan et al., 2006). Its peculiarity is that molecules (microRNAs) that the cells produced in a parent from one allele can be transmitted to the embryo through the germ cells in the absence of the allele. And amplification mechanisms can lead remanufacturing of these RNAs and their transmission to the offspring in the absence of the allele (Rassoulzadegan et al., 2006): it is a mark of a memory of the presence, in the past, in an ancestor, an allele that has not been sent. For now, the importance and frequency of such mechanisms in mammals, particularly humans, are unknown, but have recently been the subject of assumptions (Krawetz, 2005).

External environment and epigenetic inheritance behavior
A third mechanism, studied for less than a decade in mammals, is completely independent of any transmission by germ cells (Liu et al., 1997, Francis et al., 1999; Meaney, 2001; Dennis, 2003 , Francis et al., 2003; Krawetz, 2005; Weaver et al., 2005; Richards, 2006). In these cases, the propagation of changes is not the result of a transmission, but a reinitiation by the environment, the offspring from generation to generation, an epigenetic modification already initiated a similar environment among the ancestors. It may be, for example, the effect of certain foods (Dennis, 2003; Richards, 2006): footprint, memory can then be linked to a particular place or a way of life. But when the environment that initiates these changes is a particular behavior of animals, it is the community itself that can reinitiate in every generation, footprint, memory she has received from his ancestors and that transmits to his descendants (Liu et al., 1997, Francis et al., 1999 and 2003, Weaver et al., 2004 and 2005).
Obtained in the laboratory by inbreeding, many strains of mice and rats consist of genetically identical animals, whose descendants are genetically identical to their parents. Two different strains of mice or rats genetically identical can be distinguished by differences in behavior heritable, handed down from generation to generation. For example, an adult, a measurable level of anxiety more or less important - differences in how the animal feels and responds to its environment - and different storage capacities - differences in how the animal prints in him certain components of its environment, and engages him in this print - correlated with different levels of expression of receptors for hormones or neurotransmitters in certain areas of the brain.
The fact that these features are shared and inherited by genetically identical animals has strengthened the idea of ​​genetic determinism of behavior, and most of the work in these animal models, as in many others, have been focused on research alleles determine the sequence of these differences in behavior. However, a series of research initiated within the last 10 years some of these strains of rats and mice led to a profound questioning of these concepts (Liu et al., 1997, Francis et al., 1999 and 2003; Weaver et al., 2004 and 2005). Work on rat lines revealed that the fact of giving a newborn a bloodline pure anxious behavior in a surrogate mother belonging to a bloodline pure calm demeanor, that led to the newborn manifest in adulthood, behavior (and levels of expression in the brain, receptors for hormones) identical to those of its parent adoption, not its genetic parents (Liu et al. , 1997). More surprising if the newborn animal entrusted to a surrogate mother is a female, she will give birth to itself descendants who, as adults, have the behaviors and characteristics of their brain grandmother adoption, not their genetic grandparents (Francis et al., 1999).
Thus, in this case there is inheritance of "acquired characteristics". The explanation of these results schematic apparently surprising is the following. In lines of genetically identical animals to anxious behavior, the way the mother interacts during the first few days after birth, a newborn, causes methylation (that is to say, inaccessibility) in cells of certain brain regions, the promoter of a gene that cells use to produce a receptor for glucocorticoid hormones (Weaver et al., 2004). How mothers of genetic lineages calm demeanor caring for a newborn leads to an absence of promoter methylation of this gene, which remains usable by the cells. Regardless of differences in gene sequence between these two lines, the type of behavior inherited and passed on to descendants simply depends on the external environment in which the newborn has been immersed in the days following birth. More recent studies indicate that if these animals are subjected, as adults, to experimental treatments that affect the degree of methylation of their genes, these treatments canceled early epigenetic effects, changing behavior (Weaver et al., 2004 and 2005), suggesting the possibility that epigenetic changes may influence behavior in different periods of life.
Other studies conducted in different lines of genetically identical mice characterized by different behaviors in adulthood showed that behavior in adulthood could be modified by epigenetic effects of the environment even before birth (Francis et al., 2003). Briefly, in this model, mice manifest in adulthood, the behavior of their line of adoption, not their genetic lineage, provided not only that infants were reared by their mothers a few days alternative, but have previously been implanted as embryos in the uterus of the surrogate mother, who play in this case both the role of surrogate mothers, and mothers after adoption birth (Francis et al., 2003).
Thus, the widespread idea that a surrogate mother would be a mere vehicle for the embryo, and would not influence its development, and in particular on the development of certain behavioral traits - only have the genes inherited the embryo and the environment that will be after his birth - is, at least in animals, an illusion. Epigenetic constraints, such as constraints on the specific nature of gene starts at conception.
It is important at this stage to make two remarks. The first is that it is not about the mechanisms involved in disease development, but variations on behavioral traits of "ordinary" levels of anxiety, memory skills ... The second point, obviously, is he is not here but human behavioral traits of animal behavioral traits. And any attempt to extrapolate these results immediately in humans still has a dimension reductive must never forget to take into account.
But it is interesting to keep in mind that such studies suggest a very general way, many approaches currently being conducted with almost certainty a priori that will identify genetic variants, alleles, which determine changes in behavior "normal" might be illusory. There are two risks in these approaches: the first is to reinforce the idea that every human characteristic is registered and legible from the design in the gene sequence and the second is to medicalize out all the components of the uniqueness of personality human (Grandin, 2004; Sacks, 2004).

Epigenetics and animal models of lethal monogenic Mendelian inheritance and high penetrance
In the case of monogenetic diseases with Mendelian inheritance and penetrance almost absolute, such as Huntington's disease, it seems that fate is written in the genes (in one allele) and that neither the living nor the external environment can not change the development of the disease. However, recent research, conducted in mice suggest that this concept could be misleading. Can be induced in mice a disease that has all the features of Huntington's disease, leading to death by inserting its genome alleles that cause disease in humans. When these mice maintained under 'normal' animal, disease and death are triggered reproducibly to the same period in all genetically identical mice. When "enriched" cages, with objects that allow exploration, physical activity and mental stimulation, the onset of the disease, and death, are significantly delayed (Van Dellen et al., 2000). The same type of experiment was conducted in 2005 with transgenic mice that accumulate in the brain beta-amyloid deposits characteristic of Alzheimer's disease virus (Lazarov et al., 2005). It is less clear in this case (unlike the case of Huntington's disease), these changes actually correspond to those that lead to Alzheimer's disease in humans. The fact is that when you change, by "enriching" the environmental conditions, and therefore the lifestyle of these mice, there is a significant reduction in the formation of beta-amyloid deposits in the brains of these mice (Lazarov et al., 2005).
It is not known whether these results are transferable to humans. But it is not impossible that the fatalism with which we treat people who develop certain diseases is not in some cases a self-fulfilling prophecy: the belief that nothing in the environment can change their destiny, we are concerned may be enough of their environment, the first environment, the human being is the presence of others, and how to relate to others.
Thus, if the specific nature of genes and the DNA of an organism affects how the body behaves in its environment and modifies this environment also affects how the body uses its genes. Innate and acquired, and in human societies, nature and culture interact in complex causal relationships, retroactive, now called biology of "causal spiral." Experiences, particularly in animal models aimed at understanding the role of a variable trying to keep all other variables constant, can highlight, under the conditions where the environment is kept constant, the consequences of genetic diversity. However, the experiments consist of varying environmental reveal identical genome, the consequences of these environmental changes. The reductionist approach is essential to try to understand cause-effect relationships. However, it may be illusory and misleading if it leads to the conclusion that the causal relationships revealed in specific conditions summarized alone all causal relationships can be brought into play in complex and unique individuals, immersed in a changing environment.

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