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Posts Tagged ‘Twin’

Genetics is a lot like politics.  Mainly, a whole lotta fuss about sex & selfishness.  Take it from the Economist:

“Deciding whether or not to be part of a particular group, whom else to admit to your group, how to keep or share resources, and how much sexual freedom to afford oneself, one’s neighbors and one’s children are all, and always have been, lively matters of political debate.  But they are also matters that have an impact on the crucial Darwinian business of getting genes into the next generation.”

thanks Amanda-Edwards for the pic

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If I pay to have my house fire-proofed, it creates a free economic benefit for my next-door neighbors.  If I smoke and barbecue all day long, the smoke creates an economic risk or cost for those same folks.  These are examples of what economists call “externalities … a cost or benefit, not transmitted through prices, incurred by a party who did not agree to the action“.

So, what happens if I publish my genome sequence online … does anyone else get a benefit? or incur a cost?  My children?  My siblings?  What if I were an identical twin?

Do twins favor being more similar? … in which case, maybe, they might see positive externalities?

Are the epigenomes of identical twins similar?

How does your genome influence your economic behavior?

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Television icons
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just a pointer to a great SciVee episodeGenetic Contribution To Variation In Cognitive Function In Twins

Their data suggest that genetic influences on cognitive function act outside of the brain areas most commonly activated during cognitive tasks.  The areas where genes seem to exert influence on brain activity are quite variable from person to person (which is why they don’t show up in group-level analyses).  Thus folks with different genetic variability use slightly different brain areas to accomplish the same cognitive task.

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Twin studies have long suggested that genetic variation is a part of healthy and disordered mental life.  The problem however – some 10 years now since the full genome sequence era began – has been finding the actual genes that account for this heritability.

It sounds simple on paper – just collect lots of folks with disorder X and look at their genomes in reference to a demographically matched healthy control population.  Voila! whatever is different is a candidate for genetic risk.  Apparently, not so.

The missing heritability problem that clouds the birth of the personal genomes era refers to the baffling inability to find enough common genetic variants that can account for the genetic risk of an illness or disorder.

There are any number of reasons for this … (i) even as any given MZ and DZ twin pair shares genetic variants that predispose them toward the similar brains and mental states, it may be the case that different MZ and DZ pairs have different types of rare genetic variation thus diluting out any similar patterns of variation when large pools of cases and controls are compared …  (ii) also, the way that the environment interacts with common risk-promoting genetic variation may be quite different from person to person – making it hard to find variation that is similarly risk-promoting in large pools of cases and controls … and many others I’m sure.

One research group recently asked whether the type of common genetic variation(SNP vs. CNV) might inform the search for the missing heritability.  The authors of the recent paper, “Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls” [doi:10.1038/nature08979] looked at an alternative to the usual SNP markers – so called common copy number variants (CNVs) – and asked if these markers might provide a stronger accounting for genetic risk.  While a number of previous papers in the mental health field have indeed shown associations with CNVs, this massive study (some 3,432 CNV probes in 2000 or so cases and 3000 controls) did not reveal an association with bipolar disorder.  Furthermore, the team reports that common CNV variants are already in fairly strong linkage disequilibrium with common SNPs and so perhaps may not have reached any farther into the abyss of rare genetic variation than previous GWAS studies.

Disappointing perhaps, but a big step forward nonetheless!  What will the personal genomes era look like if we all have different forms of rare genetic variation?

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Church Steeple
Image by muffintoptn via Flickr

Humans are spiritual creatures – there’s no denyin’.  How & why we got this way is one of THE BIG questions of all time.  Since our genome shapes the development of our brain and its interaction with our culture, its not a surprise to see that, from time to time, folks will look for and find genetic links to various forms of spiritual and religious behavior.  Here’s a recent paper from Kenneth Kendler’s research team at the Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine entitled, “A Developmental Twin Study of Church Attendance and Alcohol and Nicotine Consumption: A Model for Analyzing the Changing Impact of Genes and Environment” [link to abstract].  An analysis of more than 700 pairs of twins found that the correlation between alcohol and nicotine consumption and church attendance (more church predicts less smokin’ and drinkin’) is more than 50% influenced by genetic factors – in adults.  In children and teens, the genetic contribution to the correlation is much less and the strength of the correlation stems more from shared environmental factors (parents, school etc.).  Is there a gene for going to church? Nope.  Are there genes that shape a person’s inclination toward novelty or conscientiousness? More likely so.  Are they distributed across all races and cultures? Yep.  Lots to ponder next Sunday morning.

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Just a pointer to onetime University of Edinburgh Professor C.H. Waddington’s 1972 Gifford Lecture on framing the genes vs. environment debate of human behavior.  Although Waddington is famous for his work on population genetics and evolutionary change over time, several of his concepts are experiencing some resurgence in the neuroimaging and psychological development literatures these days.

One term, CHREOD, combines the Greek word for “determined” or “necessary” and the word for “pathway.” It describes a system that returns to a steady trajectory in contrast to homeostasis which describes a system which returns to a steady state.  Recent reviews on the development of brain structure have suggested that the “trajectory” (the actual term “chreod” hasn’t survived) as opposed to any specific time point is the essential phenotype to use for understanding how genes relate to psychological development.  Another term, CANALIZATION, refers to the ability of a population to produce the same phenotype regardless of variability in its environment or genotype.  A recent neonatal twin study found that the heritability of grey matter in neonatal humans was rather low.  However it seems to then rise until young adulthood – as genetic programs presumably kick-in – and then decline again.  Articles by neurobiologist Jay N. Giedd and colleagues have suggested that this may reflect Waddington’s idea of canalization.  The relative influence of genes vs. environment may change over time in ways that perhaps buffer against mutations and/or environmental insults to ensure the stability and robustness of functions and processes that are both appropriate for survival and necessary for future development.  Another Waddington term, EPIGENETIC LANDSCAPE, refers to the limitations on how much influence genes and environment can have on the development of a given cell or structure.  Certainly the environment can alter the differentiation, migration, connectivity, etc. of neurons by only so much.  Likewise, most genetic mutations have effects that are constrained or compensated for by the larger system as well.

Its amazing to me how well these evolutionary genetic concepts capture the issues at the nexus of of genetics and cognitive development.  From his lecture, it is clear that Waddington was not unaware of this.  Amazing to see a conceptual roadmap laid out so long ago.  Digging the book cover art as well!

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