Archive for the ‘Actin’ Category

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One of the mental functions many of us take for granted is memory – that is – until we’re at the grocery store.  If you’re like me, you dart out of the house confident that you don’t need a list since you’re just going to “pick up a few things” – only to return home and discover (hours later when you’re comfortably ensconced on the couch) that you forgot the ice cream.  Damn, why can’t I have a more efficient working memory system ?  What’s the matter with my lateral frontal cortex ?  Can I (should I) blame it on my genes ? What genes specifically ?

One group recently reported the use of the so-called BOLD-response (blood oxygen level dependent) as a means to sift through the human genome and identify genes that mediate the level of brain activity in the lateral frontal cortex that occur during a working memory task – somewhat akin to remembering a list of groceries.  Steven Potkin and associates in their paper, “Gene discovery through imaging-genetics: identification of two novel genes associated with schizophrenia” [doi: 10.1038/mp.2008.127] examine the level of brain activity in 28 patients with schizophrenia (a disorder where mental function in the lateral frontal cortex is disrupted) and correlate this brain activity (difference between short and long list) with genetic differences at 100,000 snps spread across the autosomes.

They identify 2 genes (that pass an additional series of statistical hurdles designed to weed-out false positive results) RSRC1 and ARHGAP18, heretofore, never having been connected to mental function.  Although neither protein is neuron or brain-specific in its expression, ARHGAP18 is a member of the Rho/Rac/Cdc42-like GTPase activating (RhoGAP) gene family which are well known regulators of the actin cytoskeleton (perhaps  a role in synaptic plasticity ?) and RSRC1 is reported to bind to actin homologs. Also, RSRC1 may play a role in forebrain development since it is expressed in cdc34+ stem cells that migrate under the control of TGF-alpha (As an aside, yours truly co-published a paper showing that TGF-alpha is regulated by early maternal care – possible connection ? Hmm).  A last possibility is a role in RNA splicing which many SR-proteins like RSRC1 function in – which also could be important for synaptic function as many mRNA’s are stored in synaptic terminals.

The authors’ method is completely novel and they seem to have discovered 2 new points from which to further explore the genetic basis of mental disability.  It will be of great interest to see where the research leads next.

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I was irked to see, in today’s New York Times, a picture of a young child having his cheek swabbed so that his parents could ascertain his status at the rs1815739 C/T variant .  T-alleles at this site give rise to a premature stop codon in the alpha 3 actinin (ACTN3) gene while the C-allele encodes a full-length protein that contributes to the fast twitching of muscle fibers.  Not surprisingly, it was found [PubMed Central ID: PMC118068] that folks who have achieved status as Olympic caliber sprinters are more likely to carry the C-allele than ethnically matched controls. The company, Atlas Sports Genetics is now marketing the test, for $149 as a means to “predict a child’s natural athletic strengths”.  Holy Crap !

Its sad to think of the myriad of ways in which genetic information can be misused and misrepresented – sadder still to think of using genetic tests to deny kids the simple joy of playing with each other.  Parents may be intersted to know that among europeans and asians, the C-allele is present at about 50%, making 75% of the population either a C/C or a C/T … which, taken alone, explains very little of why a handful of individuals achieve athletic success. Parents considering paying the $149 might also wish to read a recent article by Dr. Jerome Kagan, a well-regarded developmental psychologist on recent trends in overparenting.

My 23andMe profile shows a middling C/T which is on par with my middling soccer skills.  Nevertheless, I had a great experience learning and building relationships with my pals on the soccer field, many who remain friends decades hence.

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