an international and interdisciplinary journal of postmodern cultural sound, text and image

 Volume 13, June - October 2016, ISSN 1552-5112

 

 

Postmodern Autism, or the Call of the Orangutan: Meet 13q12

 

 

Nick Ruiz

 

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And the only dramatic event in this circular maze is the unexpected about-face, (a distant reminder of Orpheus and Eurydice), which risks shattering the fantastic illusion of a double life.

Jean Baudrillard, Please Follow Me (1983)          

 

 

 

Introduction: Meet 13q12

13q12 is a stretch of DNA on chromosome 13 in the human genome. To date, its linkage with autism is exceedingly rare. In an article from 2002, reporting an observed sporadic case of autism involving 13q12, it was stated that only two previous reports of autism associated with chromosome 13 were known.[1] Subsequently, additional cases have been identified in Utah and elsewhere.[2] Currently, the Simons Foundation Autism Research Initiative (SFARI) Gene database shows that dozens of cases have now been identified involving 13q12. In fact, as of September 2016, a total of two thousand, one hundred and sixty-three genetic variations across the entire human genome have been linked to autism on the SFARI site.

SFARI shows that where 13q12 is linked to autism, it is generally identified in terms of a copy number variation (CNV) such as a chromosomal deletion, which is to say part of the chromosome is missing; or alternatively, as a chromosomal duplication, where the chromosome has two copies of a particular section of DNA, where it most often only has one. Newman et al. report that CNV duplications most often occur in tandem (some studies state the opposite; see Marques-Bonet et al.), and that some create ‘fusion’ genes at breakpoints.[3] Further, CNVs are now understood to play an important role in genetic evolution; duplicated sequences in particular, may be responsible for large scale genomic changes that offer the potentially selective advantage of new gene creation, while at the same time presenting the liability of a high mutation rate, which may lead to disease not limited to neuropsychiatric and neurodevelopmental illness.[4]

We call observable individual characteristics ‘phenotypes’; and novel phenotypes may emerge under such scenarios. Much of genetic research is focused upon the discovery of the ‘genotype’, or genetic constitution, of already established clinical phenotypes, such as autism spectrum disorder (ASD), or breast cancer, for example.

 

     Human Chromosome 13

 

 

 

 

The Scream of the Butterfly: 13q12 Duplication

 

All naturally-occurring living things, such as the family Hominidae (i.e. hominids, including the great apes), exist within a perpetual state of flux, always in a state of evolution; even if much of the ‘change’ goes unnoticed or undetected by humans. For example, Homo neanderthalensis and Homo sapiens have mated in the past, and evidence of past mating between the two species reveals itself within Homo sapiens; this startling fact, is a relatively recent observation. For example, its been discovered that heightened risk for nicotine addiction, strokes and even depression, all appear to be have been inherited by many Homo sapiens that share Neanderthal ancestral history. In other words, humanity, in its most ‘modern’ sense, presents with the symptomatology of a surprisingly ambiguous ancient admixture.[5] In another example, it has been reported (and DNA studies confirm) that chimpanzees have mated with bonobos, and that in the wild, genetic admixture “appears to have been widespread during hominid evolution.”[6]

Thus, in many ways known but poorly understood (e.g. the variable genetic process of malaria adaptation that Homo sapiens appear to share with some primates,[7] and the MHC II genes that Homo sapiens share with some primates, etc.[8]), Hominidae genetic history is intertwined to an extent the ramifications of which remain remarkably unknown and unexplored. What we do know is that while we, the extant great apes, are each remarkably different species (i.e. the four genera including: Pongo (Orangutans), Gorilla (gorillas), Pan (chimpanzees and bonobos) and Homo (humans)), we share a sort of hybridized constitution, far more closely related than most human beings probably recognize and understand. And since we share such an intimately close ancestral genetic heritage, we also share observable characteristics. Some of these traits are ordinary and normalized (e.g. variable bipedalism), while other characteristics may be recognizable as a clinically diagnosed illness (e.g. ASD). It is a link to ASD that I wish to illustrate here.

 

The Call of the Orangutan

What is a hominid? Scientifically, we all share much of the same genome, with human/ape similarity reaching its total peak at the human/chimpanzee nexus, which reaches a ~96% homology. Philosophically, the difference among the great apes appears enormous, though it is not my aim to discuss that topic here. In any event, when examining differences among individual members of just one of the great apes, Homo sapiens for example, the differences at the genotypic level may be tiny, while phenotypically-speaking differences can be quite extraordinary, as we all have probably experienced just how different human beings may be, relative to ourselves and others. And when it comes to human illness, race, sexual orientation, etc., the variation seems almost infinite. But it’s medical difference that we’re interested in here, specifically with regard to autism, or ASD, as it is now so often called.

 

Many researchers of ASD, parents of children with ASD, clinicians and even autistic patients advocate for increasing the awareness of a concept called ‘neurodiversity’, where ASD is understood as a unique feature of one’s identity, rather than an illness per se. Where genetic markers for ASD are concerned, some in the neurodiversity advocacy community may see the rapidly increasing discovery of gene markers for ASD as a furthering of the ‘autism as a disease’ agenda. It may all be a matter of one’s point of view, depending upon how comfortable one is with understanding genetics as a feature of human identity, philosophically speaking. For example, in breast cancer research, the BRCA1 and BRAC2 genes have been linked to the disease (or identity, if you choose), and many more genetic markers have been suggested.[9] Moreover, research indicates that many breast cancer patients are ambivalent about their identity and human social status after being diagnosed with the disease.[10]

     But what if human neurodiversity came to be understood in terms of our shared Hominidae heritage? What if our shared genotypic heritage began to reveal that we ‘act’ and ‘behave’ as we do, in many cases because our shared genetic heritage? One might say such a thought is unremarkable, but let’s take that line of inquiry a bit further, to ask the question: what if some human diseases, such as some cases of human ASD, are caused by our shared Hominidae ancestry?[11] I believe new evidence shows us exactly that fact.

 

I discovered the relationship between human autism and duplicative 13q12 orangutan DNA insertions quite by accident, while researching ASD. The relationship between these genetic duplications and their impact on ASD remains little researched as of today, most likely because of the grounding of such inquiry in the exploration of basic science, with little hope for corollary pharmaceutical reward in the near future. While the scientific literature shows that 13q12 duplications have been identified in orangutans, and that orangutan duplication insertions also map to human 13q12, no association has been declared between ASD and duplicative orangutan DNA insertions. And yet, the association exists.[12]

As we’ve already discussed, 13q12 duplications have been rarely identified in autistic children. This is not to suggest that 13q12 duplications will always cause ASD, but rather to identify that in an otherwise healthy child that presents with a diagnosis of ASD, with genetic testing revealing no other genetic abnormality other than a 13q12 duplication, that the 13q12 genetic duplication is highly suspect as the cause of ASD. In other words, while the genetic expression of duplicated 13q12 in orangutans has no reported deleterious effect on that member of the Hominidae family, and appears to be quite commonplace, in stark contrast, something extraordinary may occur when the very same genetic duplication occurs in humans: the birth of an autistic child. What remains to be explored now, is the incidence of 13q12 duplications in the general population of Homo sapiens, with an analysis of the increased risk for ASD such a genetic abnormality may pose to humans that possess the genetic marker.

 

Conclusion: Evolution and the Human Condition

We will continue to imagine what is true about the human condition and what may be meaningfully said about it. Buried deep in the circular maze of our souls, and our cells, remain vast tracts of what we understand to be constitutive of Homo sapiens. Though it may seem ordinary now, to talk of what is or is not in our DNA, the truth is that the lion’s share of impulses that drive us and shape our character and fate remains ambiguous, and even unknown. Perhaps unknown, forever, because the prescient blind spot of self-analysis is the largest impediment humanity has always faced. However little at a time, if we may, let us advance unmasked, no?

 

 

              

an international and interdisciplinary journal of postmodern cultural sound, text and image

 Volume 13, June - October 2016, ISSN 1552-5112

 

 

Notes



[1] Smith et al., “Molecular genetic delineation of a deletion of chromosome 13q12àq13 in a patient with autism and auditory processing defects” Cytogenetic Genome Research, 2002; 98 (4): p233-239.

[2] Allen-Brady et al., “Genome-wide linkage in Utah autism pedigrees”, Molecular Psychiatry, May 19, 2009, Vol. 15, p1006-1015

[3] Newman et al., “Next-Generation Sequencing of Duplication CNVs Reveals that Most Are Tandem and Some Create Fusion Genes at Breakpoints”, American Journal of Human Genetics, Feb. 5, 2015, 96(2); p208-220

[4] Marques-Bonet et al.,“The Evolution of Human Segmental Duplications and the Core Duplicon Hypothesis”, Cold Spring Harb Symp Quant Biol. 2009; 74: 355–362.  

[5] Simonti et al., “The phenotypic legacy of admixture between modern humans and Neanderthals”, Science, Feb. 12, 2016, Vol. 351, Issue 6274, p737, 5p

[6] Manuel et al., “Chimpanzee genomic diversity reveals ancient admixture with bonobos”, Science, Oct. 28, 2016, Vol. 354, Issue 6311, p477-481

[7] Tung et al., “Evolution of a malaria resistance gene in wild primates”, Nature, Jul 16, 2009, Vol. 460: p388-391

[8] Bontropp et al., “Major histocompatibility complex class II polymorphisms in primates”, Immunological Reviews, Feb. 1999, Vol. 167, Issue 1, p339-350

[9] Nik-Zainal et al., “Landscape of Somatic Mutations in 560 Breast Cancer Whole-Genome Sequences”, Nature, June 2, 2016, Vol. 534

[10] Johnston, Dawn. “Renegotiating the self: how eight women diagnosed with breast cancer re-shaped a sense of self-identity”, Dissertation, University of British Columbia. April 18, 2013

[11] I say ‘diseases’ because the example of autism is still largely understood in that context.

[12] Johnson et al., “Recurrent Duplication-Driven Transposition of DNA During Hominoid Evolution” Proceedings of the National Academy of Sciences, Vol.103 No.47, Nov. 21, 2006