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‘The Waltons’ Meets ‘Modern Family’:

A Pew Research Center study, “The Return of the Multi-Generational Family Household,” published long before the most recent, even higher census figures, revealed that in 2008 a record 49 million Americans, or 16.1 percent of the country’s population, lived in a family household that contained at least two adult generations or a grandparent and at least one other generation.

Those figures, according to that Pew report, represented a significant trend reversal that started right after World War II. In 1940, about a quarter of the population lived in a multigenerational home (my mother-in-law, in fact, grew up sharing a house with her aunt, uncle and cousins), while in 1980, only 12 percent did.


One of the issues that occasionally crops up on this weblog is that some readers are surprised that that I would term myself conservative, since that position seems to only imply that one wishes to slow down the inexorable march toward the future. This is a particular view of progressive history, where the future always builds upon and extends the past. Another view is cyclical, or even declinist, and over the course of human history this has been a more common tendency. Instead of hewing toward these heuristics in their extreme and exclusive forms I believe it is more prudent to keep in mind that in our current time both dynamics are important.

For example, my “phone” today would be perceived as science fictional 10 years ago. It would be inconceivable 20 years ago. Though most people don’t utilize the feature, conversations with video are finally within the reach of an average person. But these changes have come so quickly that they’re now the “new normal,” barely worth commentary.

And yet there are social trends which go in cycles. One could argue that there has been a revival of the respectability of bourgeois values in the United States since the 1970s among upper middle class cosmopolitans. Despite the power of hormones it also seems that today’s teens are sexually less experienced, on average, than those of the 1970s or 1980s. The sexual revolution not only plateaued, but receded (the push for gay marriage may actually be part of this, as homosexual activists in the 1970s were often much more radical, and would have dismissed the acquisition of bourgeois institutions into the gay subculture).

These are contemporary examples, but a modest knowledge of history will also refute excessive Whiggishness. Some would argue that the Reformation brought on sexual conservatism, as we would understand such things, only for this ‘reformation of morals’ to recede in the 18th century. In the 19th century you saw the reassertion of sexual conservatism with the Victorians, and a slow recession up to the 1960s, when the dam literally broke. Waves of cultural change and cycles suggest that the lessons of the past are often useful for the future. Social arrangements which may seen outmoded or irrelevant may not always be.

The revival of extended families in contemporary America is clearly due to economics. Unless technology can boost productivity I don’t see this trend reversing in the next 20-30 years. The dependency ratio is such that in the next generation developed societies need to reduce fixed costs like housing, and co-living is the lowest hanging fruit (and, it is within living memory of even many Americans). The piece in The New York Times presents the situation through a rose-tinted lens. And that makes sense, most living arrangements have upsides and downsides, and if the proportion of people living in these extended family situations is increasing, obviously the upsides are more appealing in the current context than the downsides.

But this is also a case where we can look to the past and other societies for lessons in terms of how it will impact our society. Though I have never personally lived in this sort of family, except to some extent between the ages of two and four (and so my memories are minimal), I know of the downsides from family lore and gossip. Just watch a Bollywood film as ethnography. From what I can gather a linear increase in the number of family members within a household does not entail a linear increase in the family drama. On the contrary, there is a very rapid increase, as inter-personal relationships become much more elaborated (this especially is true when you multiply grades of relatedness). A far greater proportion of one’s life is taken up by maintenance of household relationships. The American nuclear family is to some extent on the atomized side, but extended families tend toward hyper-sociality.

And I believe that this has consequences. The shift back toward extended families is due to the exigency of post-bubble America. Bu we may be on the way to a more thoroughgoing shift in the nature of American society, and how we relate to each other. The hyper-mobile nuclear family in the post-World War II America produced a particular kind of culture. What it lacked in family values beyond the core nuclear unit, it made up for in a commitment to civil society which could fill the breach. In contrast, societies which are ‘familialist’ often lack civil institutions and organizations because tight clusters of families can provide what in other societies would be part of the public good.

What I am proposing here is that for most Americans multi-generational living is a means toward maintaining the lifestyle and values which they hold dear, but the shift itself may change that lifestyle and those values in deep and fundamental ways. The initial trigger here is economic, with the first-order causal effects sociological. But the downstream effects may also be economic, as Americans become less mobile and more familialist. What can we expect? Look abroad, and look to the past.

(Republished from Discover/GNXP by permission of author or representative)
 
• Category: Science • Tags: Culture, Family 
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Neuroskeptic has a post up, The Coming Age of Fetal Genomics:

So they don’t. Instead, they buy a $100 test kit, they each provide a small blood sample and send it off to one of the companies offering fetal genome testing. At the testing lab, they can separate out the mother’s DNA from that of the fetus, both of which are present in the mother’s blood. By comparing the fetal genome to the mother’s and father’s, it’s easy to spot de novo mutations. If a certain gene doesn’t match either the mother or the father’s sequence, it’s mutated.

A few days later the results are back. There are several mismatches detected. Most are benign – they’re not predicted to have any biological effects. But there’s one, a deletion of a few thousand bases in a gene involved in brain development. This deletion is predicted to raise the risk of epilepsy and autism from 1% to 10% apiece. The parents now have a decision to make. The mutation is a one off, it’s not inherited. If they conceive again… roll the dice again… and it’ll be gone. Do they terminate?

Like the adverts say, “Some people disagree with this, but we say there’s only one person who really matters: your baby.”


Probably not too surprising to readers of this weblog. Years ago I joked that Armand Leroi was a “demon geneticist” for broaching the topic of neo-eugenics. At this point his article isn’t really timely, it’s almost passé! Recently on Facebook an evangelical Christian friend from high school posted a photo of a child with Down Syndrome, making the case for the value of such a life. We’re beyond thought experiment stage, CVS and some of the non-invasive methods are “online.” If Armand was a dark creature, we live in the age of Gog and Magog already. The media just isn’t reporting it for whatever reason.

But I’m not here to scare you. Rather, there is a positive and ethically uncontroversial method by which we can reduce the expected mutational load of any future fetus for a wide swath of Americans. This applies particularly to people who are the core audience of this weblog. Not only am I going to put a proposition out here, but I considered the cost vs. benefit for myself (ultimately, I decided that it wasn’t worth it for various reasons). Let me go to the section of the post which highlights what I’m getting at:

….new mutations, out of the blue, they can affect any family. A clear family history is no protection. They don’t discriminate by race or lifestyle. It’s just the luck of the draw – except that older parents are at much higher risk, especially older fathers. In the case of our couple, she’s 28 and he’s 32. Perfectly normal for this day and age – but very old in biological terms. Humans evolved to be grandparents by 32, not parents….

Sperm are replicated throughout your life. There’s a hypothesis that it is through the male germline that genetic load tends to creep into the population (or, more positively, mutations which ultimately may be the source of variation which drives evolution). Circumstantial evidence implies the children of older males may have decreased quality of life (e.g., higher rates of cancer). I recently asked a researcher who has looked into the question of genetic load in humans, and he seems to lean toward the proposition that sperm quality does decrease as a linear function beyond one’s early 20s. If you are a forward thinking person I assume you’ll already have anticipated me: massive banking of the sperm of young men may result in greatly reduced later life aggregate morbidity on the social scale.

Obviously some of the same applies to eggs, but that’s a more difficult and expensive procedure. And, the storage conditions have to be optimal. But I don’t see this as an insurmountable engineering problem. You should extend this to pre-implantation genetic diagnosis as well, take the zygote(s) with the lowest mutational load values and implant them. But that would be more controversial, due to the expense and the ethics.

I began thinking of this only a year or two back when I was going about starting a family, relatively late in life. Since I’m already “in the game,” and I can’t go back into the past to get my young sperm, I didn’t do this. And long term storage isn’t available in all locales. But if you are a young man who lives in a large urban area and has a decent disposable income, why not? Your symmetrical children with low mutational load will thank you for it.

(Republished from Discover/GNXP by permission of author or representative)
 
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The Pith: In this post I examine how looking at genomic data can clarify exactly how closely related siblings really are, instead of just assuming that they’re about 50% similar. I contrast this randomness among siblings to the hard & fast deterministic nature of of parent-child inheritance. Additionally, I detail how the idealized spare concepts of genetics from 100 years ago are modified by what we now know about how genes are physically organized, and, reorganized. Finally, I explain how this clarification allows us to potentially understand with greater precision the nature of inheritance of complex traits which vary within families, and across the whole population.

Humans are diploid organisms. We have two copies of each gene, inherited from each parent (the exception here is for males, who have only one X chromosome inherited from the mother, and lack many compensatory genes on the Y chromosome inherited from the father). Our own parents have two copies of each gene, one inherited from each of their parents. Therefore, one can model a grandchild from two pairs of grandparents as a mosaic of the genes of the four ancestral grandparents. But, the relationship between grandparent and grandchild is not deterministic at any given locus. Rather, it is defined by a probability. To give a concrete example, consider an individual who has four grandparents, three of whom are Chinese, one of whom is Swedish. Imagine that the Swedish individual has blue eyes. One can assume reasonably then on the locus which controls blue vs. non-blue eye color difference one of the grandparents is homozygous for the “blue eye” allele, while the other grandparents are homozygous for the “brown eye” alleles. What is the probability that any given grandchild will carry a “blue eye” allele, and so be a heterozygote? Each individual has two “slots” at a given locus. We know that on one of those slots the individual has only the possibility of having a brown eye allele. Their probability of variation then is operative only on the other slot, inherited from the parent whom we know is a heterozygote. That parent in their turn may contribute to their offspring a blue eye allele, or a brown eye allele. So there is a 50% probability that any given grandchild will be a heterozygote, and a 50% probability that they will be a homozygote.

ResearchBlogging.org The above “toy” example on one locus is to illustrate that the variation that one sees among individuals is in part due to the fact that we are not a “blend” of our ancestors, but a combination of various discrete genetic elements which are recombined and synthesized from generation to generation. Each sibling then can be conceptualized as a different “experiment” or “trial,” and their differences are a function of the fact that they are distinctive and unique combinations of their ancestors’ genetic variants. That is the most general theory, without any direct reference to proximate biophysical details of inheritance. Pure Mendelian abstraction as a formal model tells us that reproductive events are discrete sampling processes. But we live in the genomic age, and as you can see above we can measure the variation in genetic relationships among siblings today in an empirical sense. The expectation, as we would expect, is 0.50, but there is variance around that expectation. It is not likely that all of your siblings are “created equal” in reference to their coefficient of genetic relationship to you.


We know now that the human genome consists of about ~3 billion base pairs of A, G, C, and T. In the oldest classical evolutionary genetic models each of these base pairs can be conceived to be inherited independently from the other. In other words, evolution is a game of independent probabilities. But this idealization is not the concrete reality. To the left is a visualization of a human male karyotype, the set of 23 chromosomal pairs which the human genome (excluding the mtDNA) manifests as. Because the ~3 billion aforementioned base pairs have a physical position within these chromosomes the reality is that some are inherited together. That is, their inheritance patterns are associated due to their physical linkage. The karytope you see is clearly diploid. Each chromosome is divided into two symmetrical homologs, inherited from each parent (except 23, the sex chromosomes). The chromosomal numbers also correspond roughly to a rank order of size. To give you a sense of the gap, chromosome 1 has 250,000,000 bases and 4,200 genes, while chromosome 22 has 1,100 genes and 50,000,000 bases (the Y chromosome has a paltry 450 genes, as opposed to the 1,800 on the X).

In the toy example above the eye color locus is on a chromosome. Specifically, chromosome 15. Each individual will inherit one copy of 15 from their parents. But, there is no guarantee that each sibling will inherit the same copy from the generation of the grandparents. Let’s illustrate this schematically. Below you see the four combinations possible in relation to the chromosomes inherited by an individual’s parents from their own parents. So “paternal” and “maternal” here is in reference from the parental generation, so there are two of each. The ones inherited from the parental mother I’ve italicized.


Possible outcomes of combinations from grandparents
Mother
Paternal Maternal
Father Paternal Paternal Paternal Paternal Maternal
Maternal Maternal Paternal Maternal Maternal

The outcome are as follows:

Top-left cell: paternal grandfather’s chromosome + maternal grandfather’s chromosome
Top-right cell: paternal grandfather’s chromosome + maternal grandmother’s chromosome
Bottom-left cell: paternal grandmother’s chromosome + maternal grandfather’s chromosome
Bottom-right cell: paternal grandmother’s chromosome + maternal grandfather’s chromosome

As an example, if on chromosome 15 two siblings were characterized by the top-left cell, we might say that they were 100% “identical-by-descent” (IBD). This just means that their genes came down from the exact same ancestors. On the other hand, if one sibling was characterized by the top-left cell, and another the bottom-right, then they would be 0% IBD! In other words, in theory with this model siblings could be 0% IBD on the autosomal chromosomes if they kept inheriting different homologs from their grandparents, chromosome by chromosome (This would not be possible for chromosome 23. Males by necessity inherit the same Y from their father. While two females must share the same X from their father).

If you have a background in biology, you know this is wrong, because there’s more to the story. Recombination means that in fact you don’t invariably inherit intact copies of your grandparent’s chromosome. Rather, during meoisis, an individual’s chromosomes often “mix & match” their strands so that new mosaics are formed. So instead of inheriting homologous chromosomes which resemble exactly those carried by their grandparents, individuals often have chromosomes which are a mosaic of maternal and paternal due to the two meoisis events which intervened (one during the formation of the gametes which led to one’s parents, and another during the formation of the gametes of their parents’). If you are still confused, the following 3 minute instructional video may help. The narration has information, so if you can’t listen, the blue = paternal chromosomal segments, and the red = maternal chromosomal segments. Focus especially on recombination, about half way through the video.

http://www.youtube.com/watch?v=kVMb4Js99tA&feature=related

This process works in contradiction to conditional dependence of inheritance of variants due to physical linkage on the same chromosomal regions. In other words, though still theoretically possible with no recombination for siblings to be very different, realistically recombination breaks apart many of the associations and reduces the realized variance. In the figure above the the low bound outliers in terms of genetic distance across sibling pairs are about mid-way between the coefficient of relatedness of half-siblings (0.25) and full-siblings (0.50), and fulling-sibling ~0.35 or so (the high bounds are 0.65).

Any any given locus the variance of IBD for siblings is 1/8. Since expectation is ~0.50, you can infer from this that on a specific gene there’s a lot of deviation across a cohort of siblings. This makes sense when you consider that siblings differ a great deal on single gene Mendelian traits. But what about the whole genome? Because now you have many more “draws” the “law of large nummbers” tends to reduce the variance. The figure to the right shows the standard deviation of IBD by chromosome. Remember that expectation is ~0.50. Observe that longer chromosomes have lower deviations. This is due to the variation of rates of recombination across the genome. We’ve come a long way from an abstract Mendelian model, to the point where one can integrate in an understanding of differences of rates of recombination across regions of the genome into the model. The total genome standard deviation of IBD turns out to be 0.036, which is close to older theoretical models which predicted ~0.04. This means that if you randomly drew two full-siblings and compared the extent of total genome IBD, the highest likelihood would be that they differed from 0.50 by 0.036. Assuming a normal distribution that means that 70% of siblings would fall within the interval 0.536 and 0.464 coefficient of relatedness. About 95% would fall with two standard deviations, 0.428 and 572. About 99.8% would fall within three standard deviations, 39.2 to 61.8.

The paper from which I’m drawing the figures and statistics is Assumption-Free Estimation of Heritability from Genome-Wide Identity-by-Descent Sharing between Full Siblings. The citations, as well as follow-up papers are very interesting. It shows how modern genomics is literally swallowing whole the insights of classical quantitative genetics. Nature is one, and abstractions ultimately map onto the concrete. I’d long thought I should review this paper and its insights, as comparisons across siblings are likely going to be a future avenue of understanding the genetic basis of many traits. But I have a more personal reason for looking into this issue.

This week many of my family members came “online” to the 23andMe system. To review:

RF = Father
RM = Mother
RS1 = Sibling 1 (female)
RS2 = Sibling 2 (male)

Later to come will be RS3, another male. But his data has not loaded….

23andMe has many features related to disease risk and ancestry information. The former was not of great interest to me, as my family is large enough that I had a good sense of what we were at risk for. 23andMe told me that I was at more risk for various ailments which are common across my extended pedigree. It also told me I was at more risk for ailments which are not known in my family. And, it told me I was at less risk for ailments common across my extended pedigree. Finally, it told me I was at less risk for ailments not common across my pedigree. You get the picture. For most people there isn’t much value-add here. I haven’t even touched the issue of “odds ratios”.

In regards to ancestry, I have received some value. I suspect I’m near the end of the line in this area, unless I get into some serious DYI genetics. My involvement in the Harappa Ancestry Project is more about understanding regional patterns of variation, than that of my own family.

So we’re at the next stage: looking at patterns in my own family. The screenshot you see above is from the ‘family inheritance’, and shows the IBD between RS2 and RF chromosome by chromosome. My male sibling and my father. As you can see they are “half-identical” across the whole genome, as they should be. Of each gene my father contributes one copy on the autosome. There’s no variance here. The total 2.86 GB value is also what you’d expect, there are ~3 billion base pairs, and you’re excluding the X and Y, as well as “no calls.” I can tell you that I exhibit the exact same relationship to my father as my brother. In contrast, my sister has more segments shared. That’s because she has an X chromosome from my father. The relationship to our mother is also as expected. We’re all equally related to our parents, once you account for sex differences on chromosome 23.

Below are the screenshots from family inheritance comparing the three siblings in terms of our genomes. Remember that half-identical (light blue) has half the weight as full-identical (dark blue).

[nggallery id=30]

Here’s the top-line. I share about the same length of segments that are half-identical to both RS1 and RS2, 2.26 and 2.27 GB. But, while I have 0.60 full-identical with RS1, I have 0.86 full-identical with RS2. And here’s the even more surprising part: RS1 and RS2 have much less in common than I do with either of them. 2.09 GB half-identical, and 0.5 full-identical.

But that’s not all. 23andMe has a “relative finder” feature. It’s main goal is to find relatives you don’t know about. I don’t have any non-close relative so far, in contrast to most others from what I have heard. It may be that most of the Bangladeshis in the database are from my own immediate family! (though there are some Indian Bengalis, I’ve found only one other Bangladeshi in the database to “share” genes with) You can though include your own family in the mix. You get two different values, % of DNA shared, and # of shared segments. The former basically seems to be a proxy for IBD. I have a person of European American ancestry on my account, and they have many “relatives” matched with whom they share 0.1-1% of their genome. One individual who asked for a contact did turn out to be a very distant cousin (his surname was the same as that of a grandparent). In any case, the matrix above shows the results so far for my family. My parents are not related; they share no segments or DNA IBD. In contrast, we are all about ~50% IBD with our parents (remember that father contributes no X chromosome to sons). But look at the sibling comparisons. In particular, RS1 & RS2 share only42% of their DNA! This aligns with the earlier results. RS1 and I are a bit closer than expectation. RS2 and I are a bit more distinct. Interestingly, while RS2 and I have 49 segments in common, RS1 and RS2 have 55 in common. Why the discrepancy? Presumably RS1 and RS2 load up on the number of segments on smaller chromosomes. This seems clear in the images above.

Where does this leave us? We know intuitively that siblings differ, and cluster, in their traits. These data and methods illustrate how in the near future how parents be able to determine which siblings cluster on the total genome content level! As I have stated before, RS2 and I in particular resemble each other physically, far more than either of us resemble RS1. Could this relate to what we’ve found genomically? I believe so. Physical appearance is controlled by many different variants across many different genes, so the phenotype may be a good reflection of the character of the total genome. This can be generalized to other quantitative traits.

Finally, this has clear implications for our study of genetic inheritance within families. Classical genetic techniques had to assume that the coefficient of relatedness between siblings was 0.50. The deviation from this expectation would have introduced errors into estimates of heritability and possibly masked the understanding of the genetic architecture of a trait. But now we can correct for deviations from the 0.50 value, and so better understand the genetic basis of complex traits such as behavior.

Citation: Visscher, P., Medland, S., Ferreira, M., Morley, K., Zhu, G., Cornes, B., Montgomery, G., & Martin, N. (2006). Assumption-Free Estimation of Heritability from Genome-Wide Identity-by-Descent Sharing between Full Siblings PLoS Genetics, 2 (3) DOI: 10.1371/journal.pgen.0020041

(Republished from Discover/GNXP by permission of author or representative)
 
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Razib Khan
About Razib Khan

"I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. If you want to know more, see the links at http://www.razib.com"