The term PDD and Genetic mutation

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I was wondering how you all view the term PDD including the word disorder. Also how do you feel about our neurological condition(ASDs/PDDs) as genetic mutations. The reason I ask this is because a response I was given to giving my opinion on the cause of PDDs.

Here is my initial response:

I am leaving the member's name out to help keep their privacy(even tho you can very easily find who posted it).

Here is their response:


Was I in the wrong for voicing my opinion? I understand how this may upset some people(the big neurodiversity supporters) but I feel like their response was a bit premature and did not fully understand what I was trying to convey. What I was trying to say is my theory(one of the many) and used the general terms Pervasive Developmental Disorder and genetic mutation.

EDIT: Not to satisfied with how I wrote this. If the question is too vague please tell me as I will do my best to fix this the next time I make a thread.

All human genes are the result of genetic mutation. Describing something as mutated is akin to saying it has evolved. This is true of all living things. To confuse the idea of mutation with the idea of malfunction is to completely misunderstand genetics and evolution.

There is nothing wrong with the concept of or acronym PDD.

I think you may have misunderstood recent reports in the news about UBE3A, the subject of a recent paper in Cell.

The mechanism discussed in the paper involves UBE3A's role in chromosome 15q11.2-13.1 duplication syndrome (Dup15q), a genetic anomaly observed in a recent study in 3%-5% of individuals with autism. This means that in 95%-97% of individuals with ASD (a form of PDD) Dup15q and UBE3A was not a causative factor in their autism. This is sufficient evidence to refute the idea that all PDDs are caused by UBE3A.

The study suggests that UBE3A is one of about a thousand genes that may cause autism. This does not mean that every autistic person has UBE3A or any one combination of those thousand genes.

http://www.dup15q.org/understanding-dup ... -syndrome/

[fixing typos!]

interested

I find PDD offensive and vague. (I don't like the word 'disorder', and MR is more pervasive than autism is.)

Genetic mutation is not offensive in my opinion, but it's inaccurate for most autism cases. A genetic mutation is a genetic variation that is present in the offspring but in neither parent. Most autism is caused by a combination of genes inherited from both parents, not by mutations. This is especially true for higher functioning individuals, since syndromal autism (autism as a result of a single-gene anomaly, chromosomal condition or copy number variant) is much more likely to be a mutation and tends to be low functioning. (Most of those conditions cause moderate-to-severe MR as well as autism.)

As for the role of UBE3A, I know some autism is linked to it. Angelman Syndrome, caused by absence of functional UBE3A, overlaps somewhat with autism and increases likelihood of autism. Prader-Willi Syndrome caused by uniparental disomy (which has overactive UBE3A) has a higher rate of autism than Prader-Willi Syndrome caused by a deletion (which does not affect UBE3A activity, since the deleted UBE3A would have been inactive anyway). And in isodicentric 15 (where they have an extra chrosomosome made up of two copies of 15q11-q13), autism is higher if the extra chromosome is made up of the maternally inherited 15 (and therefore has two active UBE3A genes, plus the one on the normal maternal 15) than if it's made from the paternally inherited 15 (which has inactive UBE3A genes).

Also, the MECP2 gene is known to control UBE3A activation (mutations in it can cause Angelman Syndrome), and it's been associated with autism as well. (And of course Rett Syndrome, though I don't consider RS an autism spectrum condition.)

So clearly problems with UBE3A, especially UBE3A overactivation, can cause autism. However, I don't think we can attribute all autism to it, because most autism is polygenetic (controlled by many different genes) and most of the genes identified appear to show no interaction with UBE3A. (And if that many genes interacted with UBE3A, Angelman Syndrome would not be a rare condition.)

I suppose it's possible, but I think it's unlikely. In my opinion, the genetics of autism are kind of like the genetics of IQ - many genes exert a small impact in most people and a large impact if deleted, duplicated or mutated. (Just because trisomy 21 can cause MR doesn't mean genes on chromosome 21 cause all MR.)

There seems to be some regional/cultural variation in the understanding of the word mutation. In some cultures it simply means change. The word derives from the Latin mutare which means change, move, exchange.

There is a kind of retrograde genetic thinking that sees "mutation" as synonymous with "destructive change causing defect" and suggests "faulty gene" is a more precise expression for the same thing:
http://www.genetics.edu.au/Publications ... FactSheet4

This seems a bit primitive and anachronistic to me, being based in the idea that there is some sort of ideal blueprint for an organism and changes in that blueprint result in manufacture of a defective product. In reality, living things are complex systems continually undergoing change. There is constant exchange of genetic information with other genetic systems in the ecosystem an organism inhabits through retroviral activity and other mechanisms.

There also seems to be some idea that genetic variation can be simplistically divided into good/bad or normal/faulty categories, despite the long awareness that few genetic traits are that simple, as revealed for example in HBB variations and hemoglobin: http://ghr.nlm.nih.gov/condition/sickle-cell-disease

When it comes to genetics, oversimplification is not your friend.
http://ghr.nlm.nih.gov/handbook/mutatio ... nemutation

Given the possible stigma attached in some cultures to the word "mutation" it might be better just to talk about genetic changes and variations. The meaning is identical, so nothing is lost if one chooses not to use the sometimes loaded term.

I guess the closest thing to an objective definition of a 'faulty gene' is a gene with a nonsense mutation. (Mutated to have a STOP codon early in the protein production, so it doesn't really do anything.)

However, some nonsense mutations are normal - all known humans have a nonsense mutation in the gene that codes for jaw muscles, which causes us to have a weaker bite force than other apes. A nonhuman ape with a weak bite force might be considered to have a disability (they'd be less effective in fights, and have a harder time eating certain foods) but when it's the norm, it's not a disability.

Look in the mirror.

Everything you see in the mirror is the result of a "mutation" ( a gene that got miscopied and changed) that occurred some time in the past.

Most mutations are harmful, some are neutral, a few are beneficial. The latter get selected for and spread in the population.

But regardless of whether the mutation is benficial or not there is nothing offensive about the word "mutation". Its like saying the word "typo" is profane.

Some AS disorders might be caused by mutations. Others by normal genes coming together the wrong way (though those 'normal genes' were themselves originally 'mutations' at some point millions of years ago).

That takes care of "mutation".

On the other issue you kinda lost me as to what the issue IS.

Is it "PDD" that you're worried about? Or is the term "disorder" that you're worried about?