http://www.surgeongeneral.gov/library/mentalhealth/chapter4/sec4_1.html#etiology
Similar studies have shown that there is also a substantial genetic component to a significant number of other human disorders, including multiple sclerosis, bipolar disorder, systemic lupus erythematosus and asthma. This has been really useful in understanding the importance of genetic susceptibility to complex diseases.
But in many ways, it’s the other side of the question that is more interesting. It’s not the MZ twins who both develop a specific disease who are most interesting. It’s the MZ twins who end up with very different outcomes – one a paranoid schizophrenic, one mentally very healthy, for example – who create the most intriguing scientific problem. Why do two genetically identical individuals, who in many cases have experienced very similar environments, have such variable phenotypes? Similarly, why is it quite rare for both MZ twins in a pair to develop type 1 diabetes? What is it, in addition to the genetic code, that governs these health outcomes?
How epigenetics drives a wedge between twins
One possible explanation would be that quite randomly the twin with schizophrenia had spontaneously developed mutations in genes in certain cells, for example in the brain. This could happen if the DNA replication machinery had malfunctioned at some point during brain development. These changes might increase his or her susceptibility to a disorder. This is theoretically possible, but scientists have failed to find much data to support this theory.
Of course, the standard answer has always been that discordancy between the twins is due to differences in their environments. Sometimes this is clearly true. If we were monitoring longevity, for example, one twin getting knocked over and killed by a number 47 bus would certainly represent an environmental difference. But this is an extreme scenario. Many twins share a fairly similar environment, especially in early development. Even so, it is certainly possible that there are multiple subtle environmental differences that may be hard to monitor appropriately.
But if we invoke the environment as the other important factor in development of disease, this raises another problem. It still leaves the question of how the environment does this. Somehow the environmental stimuli – be these compounds in our food, chemicals in cigarette smoke, UV rays in sunlight, pollutants from car exhausts or any of the thousands of molecules and radiation sources that we’re exposed to every day – must impact on our genes and cause a change in expression.
The majority of non-infectious diseases that afflict most people take a long time to develop, and then remain as a problem for many years if there is no cure available. The stimuli from the environment could theoretically be acting on the genes all the time in the cells that are acting abnormally, leading to disease. But this seems unlikely, especially because most of the chronic diseases probably involve the interaction of multiple stimuli with multiple genes. It’s hard to imagine that all these stimuli would be present for decades at a time. The alternative is that there is a mechanism that keeps the disease-associated cells in an abnormal state, i.e. expressing genes inappropriately.
In the absence of any substantial evidence for a role for somatic mutation, epigenetics seems like a strong candidate for this mechanism. This would allow the genes in one twin to stay mis-regulated, ultimately leading to a disease. We’re only at the beginning of the investigation but some evidence has started accumulating that suggests this may indeed be the case.
One of the most straightforward experiments conceptually, is to analyse if chromatin modification patterns (the epigenome) change as MZ twins get older. In the simplest case, we wouldn’t even need to investigate this in the context of disease. We could start by testing a much simpler hypothesis –
Similar studies have shown that there is also a substantial genetic component to a significant number of other human disorders, including multiple sclerosis, bipolar disorder, systemic lupus erythematosus and asthma. This has been really useful in understanding the importance of genetic susceptibility to complex diseases.
But in many ways, it’s the other side of the question that is more interesting. It’s not the MZ twins who both develop a specific disease who are most interesting. It’s the MZ twins who end up with very different outcomes – one a paranoid schizophrenic, one mentally very healthy, for example – who create the most intriguing scientific problem. Why do two genetically identical individuals, who in many cases have experienced very similar environments, have such variable phenotypes? Similarly, why is it quite rare for both MZ twins in a pair to develop type 1 diabetes? What is it, in addition to the genetic code, that governs these health outcomes?
How epigenetics drives a wedge between twins
One possible explanation would be that quite randomly the twin with schizophrenia had spontaneously developed mutations in genes in certain cells, for example in the brain. This could happen if the DNA replication machinery had malfunctioned at some point during brain development. These changes might increase his or her susceptibility to a disorder. This is theoretically possible, but scientists have failed to find much data to support this theory.
Of course, the standard answer has always been that discordancy between the twins is due to differences in their environments. Sometimes this is clearly true. If we were monitoring longevity, for example, one twin getting knocked over and killed by a number 47 bus would certainly represent an environmental difference. But this is an extreme scenario. Many twins share a fairly similar environment, especially in early development. Even so, it is certainly possible that there are multiple subtle environmental differences that may be hard to monitor appropriately.
But if we invoke the environment as the other important factor in development of disease, this raises another problem. It still leaves the question of how the environment does this. Somehow the environmental stimuli – be these compounds in our food, chemicals in cigarette smoke, UV rays in sunlight, pollutants from car exhausts or any of the thousands of molecules and radiation sources that we’re exposed to every day – must impact on our genes and cause a change in expression.
The majority of non-infectious diseases that afflict most people take a long time to develop, and then remain as a problem for many years if there is no cure available. The stimuli from the environment could theoretically be acting on the genes all the time in the cells that are acting abnormally, leading to disease. But this seems unlikely, especially because most of the chronic diseases probably involve the interaction of multiple stimuli with multiple genes. It’s hard to imagine that all these stimuli would be present for decades at a time. The alternative is that there is a mechanism that keeps the disease-associated cells in an abnormal state, i.e. expressing genes inappropriately.
In the absence of any substantial evidence for a role for somatic mutation, epigenetics seems like a strong candidate for this mechanism. This would allow the genes in one twin to stay mis-regulated, ultimately leading to a disease. We’re only at the beginning of the investigation but some evidence has started accumulating that suggests this may indeed be the case.
One of the most straightforward experiments conceptually, is to analyse if chromatin modification patterns (the epigenome) change as MZ twins get older. In the simplest case, we wouldn’t even need to investigate this in the context of disease. We could start by testing a much simpler hypothesis –
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