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Hey Yin, we have a genome and a brain … what’s the relaionship?

I dunno Yang.  Lets focus on variation.  Genome sequence variation can vary with the brain  … and … gene expression can vary with the brain  … however … genome sequence variation can vary with gene expression … but … here’s a paper showing that gene expression is under the control of genome sequence variation. Purrrr.

Hey Yin, the correlation between genome sequence variation and gene expression confuses me.  I mean, gene expression can change if the environment changes right?  Doesn’t this confound research that uses genome sequence variation?

Meow.

thanks for the pic noyfb.

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I mean, how many people are really needed to run a sufficiently powered genome-wide association study?  Are there enough people on the planet?  Heather J. Cordell’s review, Detecting gene-gene interactions that underlie human diseases, seems optimistic, but, at this point, it seems a valid question … at least if you want to detect gene-gene interactions.

“The historical lack of success in genetic studies of complex disease can largely be attributed, not to ignored biological interactions, but rather to under-powered studies that surveyed only a fraction of genetic variation …”

thanks for the pic heckyeahart

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Methylation Sites on DNA

Image via Wikipedia

DNA methylation is THE key driver of epigenetic regulationWhere goest CpG methylation, then followest chromatin remodellingNOT the other way around.

“The heritability of genomic methylation patterns clearly shows that once established, DNA methylation is dominant over chromatin modifications.”

Some neurodevelopmental processes (here) seem to depend on DNA methylation, but, is this the main purpose of all this methylation?

Nope.

Our genome is a huge junk pile.  That’s right … we are built from a genome, of which some 40%, are old retroviruses, transposons and other broken legacies of foreign DNA that inserted themselves into the genomes of our mammalian ancestors.  These ancient viruses can be very dangerous and wreak havoc if they are allowed to be transcribed.  DNA methylation helps keep this from happening.  Its a HUGE job … some 60% of all CpG’s are methylated … likely THE main purpose of DNA methylation.

“The lack of cell-type-specific methylation at either enhancers or promoters indicates that DNA methylation is likely to have a negligible or very small role in development, and that the methylation changes seen at some low-CpG promoters are likely to be a result of transcriptional activation rather than a cause.”

“The data indicate that the bulk of the genome is methylated as the default state, and unmethylated regions are protected from a promiscuous DNA methylating system by a combination of very high CpG densities and histone modifications and variants that repel DNA methyltransferase complexes.”

So, we must keep in mind when reading the epigenetic literature (a methyl group here or there contributes to less anxiety) that there is a much more vital process happening (ie., lack of a methyl group here or there can lead to a lethal viral attack). Occasionally, in the process of keeping us alive, our physiological systems can make life difficult.  C’est la vie!

Also, it appears that methylation is like an enormous fire-hose spraying methyl groups everywhere in the genome to dampen the ground and prevent any small fires (viruses) from igniting. How much stock can you put in research findings that hinge on the appearance/disappearance of 1 or 2 errant methyl groups?

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Probably not … but perhaps genes that predispose to certain personality or cognitive traits that help/hinder our ability to form stable social bonds.

“Several demographic variables including marriage, having siblings and children and educational attainment explain part of the variance in loneliness. Genetic factors, both additive and non-additive, explain about 37% of the variance.”

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A LOT of genetic data is out there … and more coming all the time … easy to get excited about, but hard to make sense of.  Here’s an epic story of just one SNP.

One of the best research teams in the business performed a genomewide association study (GWAS) of neuroticism in 1,227 US Caucasion participants and found associations (P values of 10−5 to 10−6) with several markers – including rs7151262 in the MAMDC1 gene.  Later they replicated the finding in a German sample of 1,880 (P values in the same directions 0.006–0.025).

Very exciting to ponder the ways in which this SNP might relate to the development of brain systems that process emotional information!

More recently, they attempted another replication of the MAMDC1 gene for association with neuroticism in 2,722 US Caucasion participants.  This time they report, “the current analysis failed to detect a significant association signal“.

Some 5,829 people were involved in the research and the data suggest that rs7151262 may or may not contribute to one’s neurotic tendencies.  If you knew your rs7151262 genotype would it change the way you think about yourself?

I don’t know … the confusion over the (+) vs. (-) association data would make me … well, neurotic.

thanks for the photo jinxmesomethingcrazy.

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Is this what the genome has to say?

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The Jerk
Image via Wikipedia

If you’ve ever watched Steve Martin’s movie “The Jerk“, you may chuckle at the notion of having a “special purpose”.

Nevertheless, you may have wondered about your own special purpose … what are YOU meant to do?  What are some things that give meaning to YOUR life – you know – social connections (having friends and family)?, a sense of purpose (changing the world)?  a sense of self-control (earning a good wage, being healthy and having a modest home)?  satisfaction that comes from a sense of mastery (playing piano sonatas, perfecting yoga poses)?

Yes, yes, yes and yes … according to this research … these are avenues well worth exploring … keep going!!

Ask your genome, however, and it will surely give you a different answer.  By genome, I mean the long chemical strings of A, G, T, C’s that encode the machinery that constitute YOU – your brain and body.  It may have a different agenda.

The biochemical problem for the genome is that it is so damn unstable.  The long string of A, G, T, C’s has an unfortunate chemical tendency to want to break, slip, loop, slide and in so many other ways come unhinged.  We call this process mutation – and for the most part – its something that f**ks up the lives of perfectly good organisms.  Damn genome instability!

What’s a genome to do?  Apparently, one solution to this problem of mutation and the unfortunate load of mutations that can accumulate within an organism or population of organisms, is to exchange one’s DNA with other similar (but non-mutated) stretches of DNA.  Just ‘cut’ out one stretch and ‘paste’ in another, just like you might ‘cut and paste’ a revised paragraph into an essay you are writing.  No problemo!  Now all those deleterious mutations can no longer continue to pile up in the genome, since they can be cut out, and then new bits of DNA pasted in.  This process is known as genetic recombination.  In humans this process takes place in the reproductive system … its hypothesized to be the reason that sex evolved in the first place.

Yes, the genome loves genetic recombination (which necessitates having male and females who want to, um, get together) to lower the load of deleterious mutations.  What a selfish genome we have (although I’m not complaining)!

OK, so happiness research tells us that we need to have friends, self-direction, purpose, mastery etc …  and the genome tells us we need to have (ahem) sex.  So who’s right?

Check out this article  “Money, Sex and Happiness: An Empirical Study” (referencing “Measuring the Quality of Experience”, Princeton University, 2003).

… among a sample of 1000 employed women, that sex is rated retrospectively as the activity that produces the single largest amount of happiness. Commuting to and from work produces the lowest levels of happiness. These two activities come top and bottom, respectively, of a list of 19 activities.

Hmmm.  Are we a whole lot less sophisticated that we want to admit?  Perhaps.  Its not a simple answer, but interesting to think that amidst all the effort we make to attain health, close relationships, security, inner-peace, etc … at the end of the day … we just want to have sex.

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NYCSub 7 car exterior
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Playa with gold NY Yankees hat worn sideways:  Man, I’ve got mad feva for the flava of these chips.

Hipster girl with multicolor wool sherpa hat:  You better watch out playa, you’ll pass on some ill health to your kids.

Playa:  Kids! I ain’t tryin’ to have no kids.  Besides, that’s some Lamarckian shit you’re talkin’.  Dads can’t pass on stuff they get from eatin’ junk food … only girls can.

Girl:  You ever hear of epigenetic reprogramming?

Playa:  You buggin’ gurrrl.  How are my sperm cells supposed to carry all that “past history” and shit to my kids.  I mean the fucked up cheeto-eating fat cells are in my ass, not my balls.  My sperm cells ain’t got nuthin’ but some nekkid DNA coiled up in them – no room for the epigenome in MY sperm babe.  Did I say my DNA was naaaked?

Girl:  You’re balls ain’t as dumb as you think.

Playa:  Oooh Shit!  Say that again!  Please!  Tell me about my sperm cells too!

Girl:  Slow down playa.  Read the paper by Carone et al., “Paternally Induced Transgenerational Environmental Reprogramming of Metabolic Gene Expression in Mammals” [DOI 10.1016/j.cell.2010.12.008].  They show that mouse fathers can pass on all kinds of crazy changes to their offspring’s liver function depending on the dad’s diet.

Playa:  Damn!  So I have to think about what I’m eating now? what I’m puttin’ into my sperm cells?

Girl:  If you want your nekkid DNA to be with me … ha ha!

Playa: Shit, that re-programming shit is messed UP!

Girl:  Don’t hate the playa, just hate the game – the epigenetic game!

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Bronze Chola statue depicting Shiva dancing as...
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In the early 1900’s the world-famous sculptor Auguste Rodin was observed at a museum in Madras, India performing various yogic poses as he stood in front of a statue of Nataraja (Shiva performing a cosmic dance – shown here).  In fact, Rodin was nearly arrested for performing his strange contortions as the local Indian patrons and the museum guards looked on in horror, at the strange foreign man – who was moved to tears by the statue – deforming himself publicly.

This is the story told by V. S. Ramachandran in chapter 8 of his book,  The Tell-Tale Brain.  In this chapter, Ramachandran explores the brain systems that underlie our aesthetic experiences – the aesthetic jolt – as experienced by an enraptured Rodin, at the sight of the dancing Shiva.  There is much brain science and biology at work here (more posts to come).

For the moment though, just consider how deeply moved was Rodin by Shiva’s physical forms.  He wrote a poem, “The Dance of Shiva (covered here).  A master sculptor, and expert on human anatomy, Rodin’s poem reveals his deep sense of bones and musculature and is even echoed today by yoga instructors who prompt students to remain strong and poised while softening the face and emotions.  He declared the dancing Shiva, “the perfect embodiment of rhythmic movement”!

Wow!  Who would have thought that one’s ongoing voyage into yoga – often practiced as a slow rhythmic dance of shifting postures – could end up, not just in better physical and mental health, but as a living, breathing form of “high art”!  These are my favorite lines:

The human body attained divinity in that age, not because
we were closer to our origins … but because we believed in freeing ourselves completely
from the constraints of now, and we spun away into the
heavens.  It is a pleasure sorely missed…

Ramachandran explores the brain circuitry that we use when we feel the ecstasy of an aesthetic jolt – the kind that leaves us “spinning away into the heavens”.  Its an ability we all have – to feel free – & I hope I can learn to tap into it.  Yoga – with its bizarre and exotic forms – and meditation may provide a means to explore this aspect of life.

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Peanut M&M's
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The holiday foods are here – everywhere – and, even if you are steeped in a diet or other austerities, your friends and in-laws may not be.  The sights, the smells, the pleasures of sharing exotic tastes with your loved ones … I mean, if you can’t indulge now … when?  What’s a mindful person to do?

A timely article appeared in this week’s issue of Science Magazine entitled,  Thought for Food: Imagined Consumption Reduces Actual Consumption [doi: 10.1126/science.1195701]  by researchers from Carnegie Mellon University & the title says it all.  Imagined consumption, where experimental volunteers were asked to imagine consuming an M&M candy – not just the visualization of the M&M itself, but the actual eating of it – either 3 or 30 times.  The researchers then let the volunteers dig into a bowl of real M&Ms and recorded how much they ate.  The article reports that volunteers who imagined eating an M&M 30 times, when offered a bowl of real M&Ms to snack on, actually ate fewer M&Ms (about 43% less) than volunteers who imagined consuming 3 M&Ms.

This finding, wherein “imagined consumption” either 30 or 3 times resulted in less “actual consumption”, held up when investigators manipulated the food in question (M&Ms or cheese blocks),  the order in which volunteers experienced different experimental trials, and across a control trial where volunteers were asked to imagine placing quarters into a laundry machine 3 or 30 times (resulted in no differences in actual M&M consumption).  Perhaps most striking was a comparison of “imagined moving” either 3 or 30 M&Ms into a bowl (folks who imagined moving 30 M&Ms actually ate MORE afterwards) in contrast to the trials where volunteers “imagined consuming” either 3 or 30 (the group that imagined consuming 30 M&Ms actually ate LESS).  This result verified the commonly-held notion that the sight of food whets the appetite and creates an incentive to consume.

Man, M&Ms are my favorite!  The veritable gateway drug of all holiday cakes, cookies, pies and candies.  Just reading about this research has me craving a handful of those holiday red and green M&Ms right now.

OK, I will use what yogic training I have to slow down my thought processes, to increase my self-awareness and to visualize – not just the treats themselves (lest I end up eating more) but the act of eating them, savoring them and feeling the pleasure of the experience.  I’ve learned – through yoga – that this pleasure, and all the wonderful pleasures in life, are really just inside me – all part of a deep-seated inner peace and joy.  I don’t need to seek pleasures ravenously in the outside world.  The wonderful pleasures of taste, smell, texture, appearance etc. lie within me, and are accessible through my imagination, breathing and meditation.

Enjoy your holidays!  And when you find yourself alongside the desert table, realize that YOU are an amazing being – delicious on the inside – much moreso than cookies and cake.

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I probably deserve a punch in the head (see video). I will try harder to emphasize that this blog is NOT about “genes cause this” and “genes cause that”, but rather about the way we can use our genetic information as a tool – just one of many – to explore our relationships with each other, our past, other species and the environment. Still, you are welcome to punch me in the head (see video) if you like.

 

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Was checking out the new Body Browser by Google.  Yogis seem to be very knowledgeable about anatomy and physiology, so perhaps this might be a useful instructional tool.  My favorite item to view is the vagus nerve, which – as I’ve blogged about here, here and here – is nothing short of a real live Kundalini serpent inside your body (well, perhaps a little short, insofar as the nerve does not extend all the way to the sacrum and muladhara, but rather just to the swadhisthana chakra).  Seriously though, clinical studies have shown that stimulation of this nerve, brings a relief from anguish, and many a yogi knows how to activate this nerve via breathing and other bodily maneuvers.  Here’s a screenshot from the body browser.

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Playing with Google’s Ngram site … exploring the usage of words & phrases in the zillions of books currently digitized by Google.  Here are a few charts showing the frequency of a few popular yoga words published between 1808 and 2008.

There seems to have been a spike of mentions in the early 1900’s followed by a wave in 1980 and a recent wave in 2000.  Vipassana meditation and the term “namaste” seemed only to catch the 2000 wave, but not the earlier yoga wave … seems it was yoga that caught on first and then finer aspects of the practices followed later?

yogaearliest blips in 1810 then a spike in 1980

 

ashtanga mentioned in the early 1800’s!?

bhagavad – its spikes seem to presage the spikes in yogic terms?

 

anusaramentioned in the very early 1900’s!?

vipassanano wave in 1980, but tracks the 2000 wave

meditationalways a commonly used term in many non-yogic contexts

 

namaste caught on only in the recent wave

what other words might be of interest???

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Anguish
Image by matt.doane via Flickr

Do folks who experience LaLa Land get hooked on it?  Do they desire to get back there, again and again and again?  Is this why yoga teachers say that – if you let go – yoga will transform your life?  I want to let go.  I want to advance in my practice and let the transformation happen – to spend as much time in LaLa Land as possible.  I do!  I do!

But I’m torn.

my full article appears in Elephant Journal

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Your brain is a beautiful universe!  Enjoy it via meditation. Love it & spend time getting to know it.  Its a wonderful place!

 

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I feel so I can see

from ॐ // vintage psychedelics


 

 

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Sole reveals the soul

from Narkissa

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musing on mindfulness

Pommes Et Serviette. Painting.
Image via Wikipedia

(click here for posts on mindfulness)

From an essay written in 2005 by HH the 14th Dalai Lama of Tibet:

“The radical advances that took place in neuroscience and particularly in genetics towards the end of the twentieth century have led to a new era in human history. Our knowledge of the human brain and body at the cellular and genetic level, with the consequent technological possibilities offered for genetic manipulation, has reached such a stage that the ethical challenges of these scientific advances are enormous.”

Even while a great many heritability studies (some covered here) show that the brain and the mind are greatly influenced by genes, the data show that the firing of each and every neuron in the brain is also heavily influenced by one’s expectations and experiences. Even while this blog covers certain aspects of genetic biology that seem somewhat deterministic, we know that the genome does not determine one’s thought processes per se, but rather may influence the the way the brain’s neural systems interact with the environment.

One of the main purposes of this blog is to build a resource that supports the development of so-called P4 medicine” (Predictive, Preventive, Personalized, and Participatory) in the area of mental health. It has been a joy to use my genetic data as a mere starting point to reflect (ie. participate) inwardly on my own mental life – my own expectations, thought processes and emotions etc.. As I’ve noted in many posts, my genome doesn’t tell me anything definitive, but rather just prompts me to look more closely at how I think and feel and how I might be similar or different to others.

As a means to improve this ability to look inwardly, I have been practicing yoga, meditation and other types of activities that help me relax and pay attention to my thought processes. So far it has been a lot of fun and I’ve met many great folks at my yoga shala and meditation group. I think the methods used in these practices are helping a lot, but, certainly, one can develop an inward looking awareness via many, many other activities where one simply makes an effort to pay attention to the present moment. For instance, the great painter Paul Cezanne once suggested that, “Right now a moment of time is passing by! We must become that moment.” which echoes the ancient yoga sutras, “Study of the silent moments between rising and restraining subliminal impressions is the transformation of consciousness towards restraint” (III.9). So, with this personal effort underway, I hope to explore the basic biology – and perhaps even genetics – of these self-reflective forms of activity in the blog.

To follow this theme, just click on the lower right margin “TOPICS” mindfulness. These posts address the basic biology of meditation and various mental states associated with inward awareness and relaxation. Again, this is just a means to facilitate a bit of inward self-exploration. Meditating on genes and the role of genes in meditation, etc., etc.!

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Great commentary by neuroscientist Dorothy Bishop on the limits of personal genomics …

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cold outside warm inside

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