Hi, and welcome to Unit Seven Office Hours. We're talking about genes, environment, and development. so, we're coming to the end of the course. This is the last week. You guys should be starting to look at lectures for unit eight, which is the final unit. So I guess before the end, do you have anything to say, or? >> yeah. Well, maybe one thing we should point out is that it'd be great to get feedback on the course. >> Mm-hm. >> And there's two ways that participants might be able to give us feedback. One is that for some individuals who actually completed the pre-course survey, they will receive an email asking them to complete a post-course survey. So it'd be wonderful if you did that. Some of you, of course, didn't complete a pre-course survey which is okay. Don't go back and try to do it now. What we'll try to do and, and if we were successful this will have already been done, we'll try to put a thread or something on the discussion forum asking for your feedback letting us know what you thought we did well and also letting us know what we should consider changing should we do the course again. We don't know if we do the course again because it's really not up to us. But your feedback would be very welcome. >> Right? >> One other thing I, though I, I'm going to mention, before we launch in here, Bridget. Is both Bridget and I were away last week. We got back, I guess you probably got back yesterday afternoon. >> Yesterday afternoon. >> I got back late last night. We were at the Behavioral Genetic Association meetings. >> Mm-hm. >> Which is where this year, we're in Charlottesville, Virginia. And it was really pretty exciting. >> It was a great conference >> It was real good conference and Bridget gave her first oral presentation. >> Oh, I did, I did. >> A behavioral genetic analysis of relational aggression. There were some exciting results on schizophrenia that >> Oh yeah. >> People who follow this literature you'll, I would think in the next month or two you'll hear about a new even larger GWAS. >> Mm-hm. >> of schizophrenia. Where they've now, I think the, the GWAS we discuss in this course they had identified 20 or so hits. >> Mm-hm. >> It's now over, over 100. So real progress is being made there. And there was a lot of discussion also about intelligence, another topic that we've talked a lot about in this course. >> Mm-hm. >> So, it, it was a lot of fun. >> Yeah. >> It was fun to go there. Bridget did a great job. So and, and what we talked about in, and then actually, some of the people at the conference knew about this course as well. >> Oh, yeah. >> So they weren't taking it because they're experts but, but they knew about it. >> Plenty of people were signed up so they could see how you were teaching it. >> Oh, Okay. [CROSSTALK] So, anyway. So it was fun. And progress continues to be made. So. >> Yes. >> That's good. >> Great. Well, we actually have a lot of questions for this week. People are really interested in the topics that we've covered the last couple weeks. So why don't we jump right in. >> Mm-hm. >> Our first questions are about shared environment and non-shared environment. Our first one comes from Adam. And he says, It seems the definition of shared environment is almost, almost unquant-quantifiable. How can we know if an environmental influence is having the same subjective impact on two individuals? Could the nebulous definition have an impact on the studies that show a negligible effect of shared environment? >> Okay. Adam, right? >> Adam. >> So, that's a, that's a great question and I, and I think we'd have to agree that the, the definition of shared environment is a li, somewhat ambiguous. It, it is defined in terms of it's effect rather than objectively and I think that's what Adam's getting to here in the question. And that is ambiguous nebulous as he puts it. A couple of things about it though and then I'll try to answer his specific question about well could we ever tell if a specific factor affected individuals differently? Really throughout most of div psychological history psychologists, when they studied children in the families studied one child per family. And this is a point that the eminent behavioral geneticist Robert Plomin makes. And kind of the, the implicit assumption there was that other children in the family were being socialized in a similar way, and so there was almost no need. And it was logistically difficult to do that. And it really wasn't until behavioral geneticists came along, where they found that, gee, things are actually quite different for different children in the family. And, maybe to, to my mind the easiest way to understand what shared environment is getting at, is to think about those adopted siblings. >> Mm-hm. >> Individuals who are not genetically related, that grow up together in the same home. How similar are they psychologically? Well, turns out that for most psychological traits they're not very, similar. But, and this gets more into Adams point, is that okay so that's defining shared environment by its effect. Does the environment of growing up together affect psychological similarity in these two genetically unrelated individuals? And for, the answer to that is for the most part, no. >> Mm-hm. >> It is for IQ, but that looks to wear off with time. What if we tried to look at objective indicators in the environment and tried to see? Certainly people try to do that in adoption studies. What's the impact of being reared in a home where you have parents who are divorced? But what Adam wants to get to is not just whether or not you have parents who are divorced, but maybe that divorce affects some children differently than others. How can we begin to unpack that? Well actually the way to begin to unpack that is really the, the notion, what he's getting at I think is the other gene environment interplay, process, and that's gene environment interaction. If the same environment event, environmental event is impacting children differently it may be because they have different genetic constitutions that make them more or less susceptible to that environmental event. The way that researchers, is it, I think Adam is right. It's a difficult concept to, to really design studies to explore. But the way researchers are trying to do this is to classify children phenotypically. High sensation seekers, or individuals with ADHD versus their siblings who don't have ADHD. If you look at children that are classified differently, when there is an event in the family, do they react to that event differently? So there is, kind of, growing research on that. That's how, the way that, that people would do it. >> Okay. Our next question comes from Ralph. And Ralph says siblings reared together strive to create individual identities so that they will stand out. Is it possible that shared environment is actually causing differences in personalities that are being attributed to the non-shared environment? >> yeah. Well, that's possible. So, right. You try to find your niche if, in, in a sibship. So if my brother's dominant maybe I, I try to be a little bit more retiring or less of a leader because he's dominant in my sib-ship. Does that go on? I'm sure some of that goes on. How important it is I'm, I, I confess I'm really not sure Bridget. I think one thing that I would point to though and it's kind of at a general level. If that were really, really a powerful force then we might expect reared together twins to be less similar than reared apart twins. They certainly aren't less similar. They're about equally similar in, in personality factors. So although I think there probably some of that niche selection that goes on where each child in a family is trying to find his or her niche. >> Mm-hm. >> I don't, I, I really don't think it's, it's that powerful in the, in the total population. >> Okay, so our next questions have to do with gene environment interactions. And the first one comes from Maria, and she said, I would like to know if there's a possible but reversed GYE for antisocial and rule-breaking behavior versus GCA, or general cognitive ability. That is, does the heritability of anti social and rule breaking behavior increase in poor dis, and disadvantaged homes? Because adoption often involves moving from a disadvantaged rearing environment to a better one, the adoption studies would be pointless in this case as a methodological tool, to answer the question. Do we have reasons to assume that a set of genetic factors influencing antisocial and rule breaking behavior are not fully expressed in advantaged homes? >> Okay, so, processing that. Maria, was that it? >> Maria. Mm-hm. >> So, an interesting good question. the, the questions are getting better. >> They are. >> Obviously, as we're going through it a little more challenging. so, with general cognability, which is what we saw in unit seven, the one we're talking about here. What you see is that in disadvantaged environments, the general consensus, and actually there's a lot of research also. >> Mm-hm. >> Reported at the conference on this particular phenomenon. >> There was. >> That in disadvantaged environments the heritability, or the genetic influence on general cognitive ability is diminished. And, and a way of thinking about it is that those, those impoverished environments don't provide the opportunities for an individual to fully realize his or her genetic potential. >> MM-hm. >> So, Maria's asking about the compliment. Antisocial behavior. And actually, if we go back, we, we too, we had an example of this. And, so, the one thing that I might quibble with Marie on is, I think adoption studies, they're not ideal. But I think they are a way to begin to explore this. The reason they're not ideal is, precisely for, for the reason that she points out. Is that on average adopted families are advantaged. >> Mm-hm. >> There is variability in adopted families. And if we go back to unit two we did see what Chu's really predicting here and that is if we look at the Kata Ray study we found that in a advantage, a highly advantage a nurturing adoptive home, the genetic effect, which in that study was, was indicated by having a, a birth family background of antisocial behavior. The genetic effect on childhood aggression was greatly diminished. And so the genetic effect is actually only seen in disadvantage or relatively disadvantage [UNKNOWN]. So she's right that you kind of get a complementary forum of GE interaction. You get the diet that's assess, a stress form. When you're talking about an undesirable trait like. Anti Social Behavior and I think she's largely right that, maybe the adoption isn't the ideal way of looking at this. But it isn't a bad one either. >> Mm-hm. >> And we saw an example of this early on in this course. >> Our next question comes from Anna. And Anna asks, if the Faulkner Model assumes that there's no gene environment interaction or correlation. How can we be, or how can it be used to access gene interaction? so, that's a good question as we get towards the end of the course. The standard Faulkner model assumes no gene environment interaction. And, now we've really, you know, we spent a lot of time, we've kind of moved beyond the Falcon model in the course. At. >> Mm-hm. >> At least I hope we have. And we've spent a lot of time talking about gene environment interaction correlation, but yet the Falcon, and, and discussing whether important phenomenon, but the Falcon/ model doesn't deal with that. I think. It's well to point out again that that's one of the reasons why we should always take with a, a, a small grain of salt anyway, the estimates that come out of the Faulkner model, they're approximations. So it is just a limitation of that standard Faulkner AC model. Can the Faulkner model be, as, an as, it, suggesting here. Can it be extended to incorporate these other, more complex forms of gene environment interplay, like correlations, interactions. Yes. As you know, it, it can, the biometrics and the quantitative genetics. Gets more complicated but certainly people do, do that and in fact the Turkheimer result which we saw I think in this, in week seven, where the heritability of IQ increase with social economic status of the rearing home. That really was observed by taking the, the basic Faulkner model and enhancing it. To see whether or not those ACE estimates, AC and E estimates actually varied as a function of rearing and social class. So, yes, it can be done. It is being done and in fact we've seen some illustrations of that in this course. Okay. Our next questions comes from Patricia and she says, Serotonin provides the individual with a sense of well being. So it's beneficial to have it persisting in the synaptic cleft for longer, a longer period of time. SSRI drugs that inhibit the reuptake of Serotonin help to alleviate the symptoms of depression by allowing Serotonin to remain the synaptic cleft longer. Very good, so far so good, but having the short form of the allele causes less transcription of the reuptake transporter; which would allow serotonin to remain in the synaptic cliff longer. And yet these individuals are more at risk for having depress, depression. Can you explain this paradox? >> Okay, it's very, it's a very insightful. Patricia? >> Patricia. Mm-hm. >> Patricia, very insightful question. And, you know, actually I, Patricia, I think I'm going to begin just by trying to restate because otherwise I'm going to get confused because [LAUGH] >> [LAUGH] >> You keep track of a lot of things here. So a standard treatment for depression- >> Mm-hm. >> Is SSRIs. >> Mm-hm. >> Selective seratonin reuptake inhibitors. What do they do, they block the serotonin transporter. The serotonin transporter transports serotonin into the presynaptic neuron. So it takes it out of the the synaptic clefted essentially down it, it down regulates serotonin. >> Mm-hm. >> It, it, it, it reduces its availability. Okay, that's' fine. So we have this polymorphism. In the gene that codes for the serotonin transporter. And the polymorphism that's been most widely study, in fact, I think it's the most widely studied polymorphism in psychology, is in the promoter region of the gene. It's actually an insertion, deletion, but, the alleles are called the short and the long allele. So, the shorter [INAUDIBLE] which is the one she's referring to here is a [INAUDIBLE] that produces less of the serotonin transporter. So you might think you produce less of the serotonin transporter, isn't that kind of like SSRI's? >> Mm-hm. >> In that SSRI's block the serotonin transporter. So if you have less of the serotonin transporter, more serotonin availability, less risk of depression. The paradox, as Patricia's pointing out, is uh-uh, that isn't the way it works. The, if there's a risk allele here, it's the short allele. The one that, a priori, you might think is protective because it seems like it mimics SSRIs. >> Mm-hm. >> Why is that? Well, if she'd asked me that question two weeks ago, I would have thrown up my head. I don't know. >> [LAUGH]. But actually, within two weeks, there was a paper published. And I put, I put a link to the paper. >> Mm hm. >> At least the abstract of the paper, on the thread, in answering her question. A paper published in Molecular Psychiatry, which is a very good journal. And basically, it's a paper that they're studying. I believe it's mice, it could be rats. It's rodents of some type. Is, that there's a developmental phenomenon going on here, is what they argue. And with some. Evidence, there's some good evidence in the paper. And that is that if you block the serotonin transporter early in the development of the rodent. >> Okay. >> Then the rodent gets exposed to high levels of serotonin. That, apparently in, if, if that occurs early in development. It has this other effect later in development of making them at greater risk for, what's the animal analogue of depression or anxiety. And, it may be that early exposure to high levels, I'm not a neuroscientist. And, I don't think you are either but there are probable some out there. It, it may be that high exposure early on. In development, desensitizes the post-synaptic, synapses or something. Something must happen. So, yes it's paradoxical, but maybe the resolution of the paradox is that, what's going on is bringing in development, which is something we did talk about, this time. >> And, correct me if I'm wrong, but looking at the short and long alleles, is it- The long allele that's actually more receptive to SSRI drugs? >> Yes. [INAUDIBLE] the, if, yeah. If there is, if there's an interaction between whether or not SSRIs are more effective, depending upon your genotype. It appears to be the long allele. The reason I'm equivocating a little bit on that, is that. I don't think there's a lot of studies at this time, so. There's certainly multiple studies, there's maybe three or four, maybe more than that, but, but the samples aren't large and so I'm not sure that it's, it's an absolute solid result. But if there is an interaction, it, it, you're right. I think the s's or i's look to be more effective. With individuals having depression with the long allele, i.e., producing more serotonin transport. So, that's not apparent, that would fit with the model she's giving us here yeah. >> Our next question comes from Marshall and he says, if certain individuals develop a tolerance to a certain environmental influence. Thereby minimizing their likelihood of suffering negative consequences. Does this mean that genes are mutable by design? For example, a cousin has a serious allergy to bee stings and underwent controlled exposure to bee toxin to develop resistance. After a while, he was no longer susceptible to bee sting reaction. If his genes somehow changed, would he pass his newly developed resistance on to his future children? It de, it depends on what he means by if his genes were changed. His nephew or cousin. >> Cousin. >> Cousin. so, it, it's a pretty complicated question but. I guess there's a couple parts to it. One is, does repeated exposure affect our genes, I guess, is part of it. In a way that kind of makes them less sensitive to that exposure. Well, that's kind of like what we just talked about with the serotonin transporter. It may be that repeated exposure affects how genes are expressed. I'm sure there are probably examples of that. >> Oh, sure. >> And it could affect it in multiple ways but it might have affect it epigenetically. I don't think it affects it, and this is where it's a little un, I'm a little unclear as to what it what Marshall's asking. I'd only think it affects the sequence of the gene. But it might affect methylation marks or whatnot. >> I think he was asking about if they were mutable. So I think he is getting at this more methylation patterns or. >> Okay. So there might be some epigenetic phenomena. Then the second part is, so that may happen. Do I have examples of it? I don't personally have examples of it, but there may be examples in, out there at this point, I'm just not familiar with them. The second part of his question, could these [UNKNOWN] be transmitted across generations, we've talked about several times here. I won't go into great detail. That's epigenetic inheritance. Can you transmit the epigenetic markings across the generations. That, I think, is more debatable. >> Jury's still out, right? >> Yeah, I, you know, there's certainly examples of that in other organisms other than humans. And I think there are certainly some very good scientists who believe. >> Mm hm. >> There are examples in humans. But I think, I think it's, I think we're still learning about it. So. >> Our next question comes from Debra. And she says, I'm a little confused about what the environment might do to affect eye color. I though eye color was a Mendelian trait, at the remarks about the genes carrying blue pigment. Which seemed to be presented as a joke, made by my confu-, made my confusion worse. What sort of impact can the environment have? >> Okay. Sorry to confuse Debra. It wasn't a joke though. [LAUGH] It's okay, maybe I laughed, I guess. >> [LAUGH] >> I shouldn't do that. >> So, yeah, Debra's, I hope I didn't suggest. I don't think it would've said that eye color is a Mendilion trait. Its, it, although a lot of people do believe. >> I think it's commonly thought of as a mandilion trait. >> Yeah, in the but is it, mandilion in the sense like there's one eye color gene. >> Mm-hm. >> And you know, I don't know blue eyes are, are thought to be recessive and what not. That isn't. Quite true. I don't know all the genes involved, but there are certainly multiple genes involved in, in terms of eye pigmentation. So if, if I had suggested it's Mendelian, then I was wrong, that certainly isn't the case. The reason I was using eye color, though, as an example is to try to differentiate this notion where some people say well, it does, what behavioral geneticists do don't matter because every behavioral trait we have depends both on our genes and our environment and so it's kind of silly to ask well, what about our genotypes is important and what about our environment is important? If we think about our eye color, you, we don't have eye color just because our genes, because our genes are just a sequence, of nucleotide bases. There's nothing but, it, it provides a code. The pigmentation comes from our environment. So at the individual level, both the genes and the environment are operating. But when we compare individuals, we, one individual might have brown eyes and the other blue eyes because of their genes. Or, actually, there are some environmental events, like a head trauma that could change your eye color. So there are environmental things that can create differences as well. So I was trying to make that distinction between the biometricians' focus on individual differences. Why some people have blue eyes, other people have brown eyes. Versus the developmental interactionists, who argue: well, blue eyes obviously depends on both your genes and environment when you talk about the development of a given individual. And, to, to try to draw that distinction. >> So let's switch gears a little bit, and go back to the topic of general cognitive ability. Our first question comes from Edwin, and he asks. Both d-z twins and parent-offspring are first-degree relatives. Yet general cognitive ability correlation for them are 0.6 and 0.42. What accounts for this huge difference? >> Well, that's a good, a good observation by Edwin. It One possibility, although I don't think it's actually the reason but, just to kind of reflect back on, I don't know what it'd be, week three I suppose in the course, it could be non-additive genetic effects. Right, genetic dominants contributes to sibling and dizygotic twins are siblings, sibling similarity but doesn't contribute to parent offspring. I doubt that's the explanation here though, but it could be. More likely, are two factors. One is the shared environment. >> Mm-hm. >> Most of those sibling studies, or the Dysegar twin studies, I should say. That were in that aggregation, are based on children in adolescence. so. They, they're sharing an environment. The parent offspring are not sharing an environment. So that's probably a very important factor there. >> Mm-hm. >> The other factor is that parents and, and offspring are at different developmental stages. And we've seen in this unit that development can have an impact, on the importance of genetic and environmental factors. Whereas siblings are at this, even if, in fact, it may have an impact just on the importance of genetic factors. So, that their, the parents and offspring are at different developmental stages, the effect of genotype for the two might not be the same. Whereas, dizygotic twins are the same age, they're at the same developmental stage. Okay, our next question comes from Thomas. And he says that there's a famous case study of a girl called Isabel who was raised by her deaf-mute mother in total isolation from the rest of the world. She lived in a dark attic room with her mother and did not have any toys or books or other sources of recreation and education. When she was found by the authorities and placed in a normal environment at age six,. She was unable to speak among other disables. >> She was, I'm sorry to interrupt. >> Unable to speak. >> Unable to speak when, when she was placed, okay. >> When she was placed. >> Mm-hm. >> Among other disabilities, and was found to have an IQ of 30. However, once, once she was away from the terrible environment and received special training, she started to develop at a very fast rate and by age eight. She was able to read and had an IQ of about 100. And was attending an ordinary school. My question is that if Isabel had been found only years later, would she still have recovered? Is there a consensus that such recovery from childhood deprivation is not possible after a certain age? That's an interesting, I'm actually not familiar with this case but there are, >> You've heard of similar ones? Yeah. >> Yeah, there are other ones in the literature. There are these case histories in the literature of these sadly deprived, severely deprived, children, and the impact, on their development. Is there a critical period. When developmentalists talk about critical period in this context. Generally and, and probably, was there Isabel, was that her name? >> Isabel was her name. >> Yeah, in her case. There probably, the focus would be on language. There is another case that I'm more familiar with and it speaks directly to Moss's question. Genie spelled "genie" like genie in the bottle. G, E. N, I, E. And Jeanne was also reared in isolation, actually in a small room, she was tied to a chair. Not spoken to. I think, I think she lived in L.A, and she was not found until 13. She never developed. A normal language or her, her intellectual development was impaired. What language theorists have, or at least some of them, is that there is a critical period of the acquisition of language and if you're not exposed, I think what it, the thought is, if you're not exposed. Pre-puberty, then you will not develop normal language. And so in Isabelle's case, right? You, I guess she was found at age six. >> Six. Mm-hm. >> She then was exposed. In Jenny's, Jean, Jeannie's case, she wasn't found till 13. She never developed. She had very, very rudimentary. Language. And that actually relates to other aspects of language. I believe that the notion is if, if children are exposed to other languages prior to puberty, they can develop facility to that language without an accent. But if you wait until after puberty, they can never quite get the accent right. It's difficult. Even in the case of Genie it's, these case histories are kind of difficult to unpack, because you really don't know what Genie was like prior. >> Mm-hm. >> To being, clearly being severely deprived affected her, but what was she like before? Was she intellectually disabled before? You don't know, so. In general I think there is this notion that there's a critical period for language acquisition that in terms of intellectual development, certainly factors that are important is the duration and the severity. >> Um-hm. >> And for other behavior and you're, you're probably familiar with the, the studies of the Romanian. Adopted children that, even those children, I don't know about their intellectual development, but their behavioral development. Even when they're taken from what, what, what was a deprived environment growing up in the Romanian orphanages, at age two and a half and three, they sh, still show deficits later. >> Mm-hm. >> So, even children. Placed in different, enriched homes at age three. Can carry a burden from these early exposures. So it's kind of a complicated question. >> It is, but a good one. Very interesting. Okay, our next question comes from Edwin, and he says in lecture six B Professor Miguel talked about general cognitive ability correlations for biological relatives. Weird together versus weird part, and he says I can understand monozygotic twins and full siblings weird together or apart. But there's a column for parent offspring, how is that done? What is the sample size, how is that different from general correlation step, correlation study and adoption studies? >> I guess I'm not a, complete sure of the what Edwin is asking here, is. Maybe he's asking well how do you ever get these, >> Parent offspring [INAUDIBLE] together, veered apart? >> Parent offspring but, veered apart. Most of these studies come out of, you know maybe it's the question is, well how do you get the birth parents if somebody is adopted. So I'll pretend that's a question, even if it isn't. Cause otherwise I don't understand the question, I'm, I'm sorry. A lot of them come out the, the, the registries. >> Mm-hm. >> The Scandinavian registries, which is a limitation of course. because Scandinavia isn't like necessarily like the rest of the world. But in the Scandinavia countries, the, the parents are registered in the system and, the, it, in there, and they, there academic scores might be registered as well or other things. >> Mm-hm, mm-hm. And so you can actually do these studies without ever seeing the birth parents. There are studies like the Colorado Adoption Project that you're very familiar with because you're in Colorado. Where they actually contacted the birth parents at the time the birth parents were placing their child for adoption. And asked if they would undergo assessment and, and they a pretty good percentage of them agreed to do that. >> Yeah. >> So sometimes it's possible. It's not easy but it is possible sometimes to get information about the birthday. >> Let's switch gears again a little bit and move on to the the discussion of GWAS, or Genome-Wide Association Studies. Our first question comes from Linda. And she says: In the units on schizophrenia and IQ, you stress the huge sample sizes needed to identify candidate genes with very small effects. Could you comments on the work of David Piffer, where he describes using a factor analysis for detecting. Signals of polygenic sections of genes with overlapping phenotypes, but located on different chromosomes, potentially decreasing the number of snips that are included in a genome-wise association study. Reducing the multiple testing and required sample sizes and consequently financial costs. Are you familiar with this paper at all? I'm not familiar, but, em, maybe what I could do is, is discuss the question in, in, in, in general terms and actually, maybe relate it back to the conference that we just attended. Linda's, you know, right to point out that, wow, I mean, you need gigantic samples here. >> Yeah. >> One of the things that we heard about. And, the conference was the consortium to look for genetic variance for height- >> Mm-hm. >> Which is, appropriately called the giant consortium. Now has a half million people. participants. Genotypes on a half million people. All these consortia, the sample sizes keep growing and growing. And I think what Linda's getting at, without. My knowing this specific work here, is could there be an alternative statistical way of, of, of doing something with data on smaller samples. There's a lot of work that tries to increase the signal in various ways, and again not knowing this one but, it sounds like what they're doing here is maybe building haplotypes. >> Yes. >> Rather than testing individual snips. Other things is to. Try to look at multivaria, multiple phenotypes at one time. I, this is no better than my opinion. I think at this particular point in time, a lot of people are thrilled that we actually have a vehicle for making progress. Where we didn't have a vehicle before, with the candidate gene approach. So most of the resources, I think. Even though it seems very inefficient, probably, to many people, most of the effort now is going into building these very large consortia, identifying the variants. The goal, the ultimate goal here, isn't to identify every variant but is to identify a sufficient number of variants. So that the pathophysiological pathways can be identified. >> Mm hm. >> And given that. I think, probably, there's, there's always going to be efforts to try to improve on just the standard, one snip at a time. But we know the one snip at a time can work. And, and people cooperate quite a bit as we're learning at these- >> Yeah. >> At the meetings. And so, scientists cooperate in, in sharing their data. And so, we know we can build large samples and I think over the next, maybe about five years, a lot of the effort's going to go in just trying to get very, very big samples. >> Yes, it does sound that way. Our next question comes from Sandra. And, she's interested in what you're doing, Matt. She says, what are your current research projects? Also, what is the maximum sample size for suitable living twins that could be studied, and about which new data could be collected? With the current. Need that has been identified for larger sample sizes in many areas of behavioral genetics. Does this raise any concern regarding the validity of twin and adoption studies or force any new approaches? >> Okay. So what was? I'm sorry. >> The first part was your research. >> Now, now. I'm not going to answer that one actually. I apologize. It threw me off so much that I will, I lost track of the name so much. I apologize. So what's ? >> Sandra. >> Sandra. Okay. So Sandra, I wont bore you about my research. Thank you for asking, but, but I do research on twins and substance abuse and aging, actually. >> So she. >> But it actually kind of related back, the other part of her question, I will try to address. It related back to the previous question in, which I think. In a, in a kind of an insightful way, I think, is, is what she's raising is an important question that researchers do discuss now. So if you want to get bigger and bigger samples, what's the downside of doing that. And there are some downsides to doing it and, and maybe I'll just mention a couple. One is that. One is that you end up, if you, if you want 20,000 individuals who have schizophrenia, you tend to then depend, it, it's, it would be very hard to interview that many people. >> Mm-hmm. >> So you te, te, tend depend upon what assessment exist in administrative databases. That may or may not, I, I, mean it's probably not the best phenotype in the world. So, so maybe the phenotypes in these large scales, there's probably some loss of fidelity in measuring the phenotype. So that's one downside of getting these, ever, ever, larger samples. Is that there's less effort in being placed on getting a very good measure of the phenotype. But again something I, maybe you've heard this at the conference. One thing that was pointed out in this very large, giant consortium on height, that it's been very succesful. Well, how do they measure height? Well, sometimes people just tell them their height. Sometimes they're actually measured. So it's maybe not the best way to measure height if you are actually setting out to measure it. But it seems to work. >> Mm-hm. >> So, but that's one downside. Another downside that people have been concerned about. Is is that you tend to go to certain countries. And, and a lot of those countries are Western European or really, Northern European, Scandinavian countries, because that's where you have these large registries. And in doing that, that might really significantly. Limit the environmental variability, people are, are studying. I think, the researchers doing this. I'm sure they're very sensitive to this issue. >> Absolutely. >> And maybe the hop is, and probably the expectation is. At this stage of discovery, that's the resources we have. Let's use those. And then, eventually shift to where we focus on it. Or at least, we, we, remove that focus, and study. More diverse populations. The last thing that actually came up in the conference is, well, what does this mean for young people, like you? >> Yeah. >> You know, if you need a sample of 100,000 individuals what do you do? I mean, that's a really hard thing to do. And it's something that I think the funding institutions, the training institutions, the research. Institutions are, are discussing now >> Mm-hm. >> is how to make sure their opportunities for, to not only develop young scientists, in this era of big science, >> Mm-hm. >> but also to give them the opportunity to develop their own career, so that they will be the leaders. Ten, twenty years down the road. And I think there's a lot of effort now going into this. Recognizing that it's going to be hard, at least in behavioral genetics, at this time stage, the development of the field. For one person doing his or her own twin study at the University of Minnesota to have much of an impact. >> Yes. Because it pic, has become big science. >> It is. >> Yeah. >> Our next question comes from Dupali, and this is switching gears a little bit. But it says in one of the lectures of week five, there was a mention about psychiatric phenotypes. What is the difference between a psychiatric phenotype and psycho psychological phenotype? >> Yeah, the, the difference is, is probably subtle. In that psychologists', study of broader array of phenotypes, the way I've been trying to use the terms is psychiatric phenotypes deal with mental health issues, whereas psychological phenotypes even though psychologists certainly study schizophrenia and substance abuse, psychological phenotypes are, are focused on normal range variations. Okay. And, our last question comes from Tys. And, it says, in Unit 4, Professor McGue said that, in every cell, one chromosome is one inactivated. So, I didn't understand how males would have more vulnerability to intellectual disability if the recessive gene, if that causes the disease, for example, will be more likely to occur in males. Okay so this I, I think we've had this question before. But it's a good question. It's, it's, it's well to point out. Which is, if females have one x chromosome, in, inactivated, then aren't they effectively like a male with one x chromosome? And therefore why is it that males are more susceptible? To X-linked recessive conditions, like intellectual disability. I'm going to give a short answer to this but I think it's an important question. I, I don't want to short it for that reason but we've talked about it in detail before. The short answer is because, in different cells, different X is inactivated in a woman. If a woman is a heterozygote, take a population of neurons, in some, and let's say there, she's heterozygote for a condition that in the recessive state would lead to intellectual disability. In some of her neurons. The mutant allele, the one's that associated with intellectual disability will be expressed, will be, that will be the active x. In other of her neurons, the other x, the other x will be active and the non-mutant allele will be expressed. It probably is that she has enough neurons with quote-unquote the good gene being expressed to compensate for those neurons where the bad gene is being expressed. So that's why women are protected. Okay. Perfect. Well that was our last question for this week. Good luck with your last week here for unit eight. And, again, don't forget to fill out that post-course survey and also get on the forums and let us know what you thought of the course. Thank you. >> Thank you. Thanks.
