Friday, February 12, 2010

Mark/Tom: Summary of gene discovery

Mark Bulger has sent me a summary of the paper. Thanks! Here it is (my extra comments are in italic.)

In an earlier study (Am J Hum Genet. 2005 Apr;76(4):647-51), the Drayna research group found a high likelihood that there was a gene or genes related to stuttering on chromosome 12 in a population of Pakistani families. In this study (February 2010), they used DNA sequencing and related technologies to identify the actual genes that produced the results in the earlier study.

Two paired groups were examined: Pakistani families in which stuttering is common together with a control group of Pakistani non-stutters, and American and British stutterers, with a similar control group of matched non-stutterers.

Three genes were found to have variants that occurred in the stuttering groups, but not (or rarely) in the non-stuttering control groups. The changes observed in the DNA code of these genes provide a different instruction for the cells to produce a protein and would be expected to result in a protein with a different function to the protein ordinarily produced without the change. Mutations in two of these genes have been shown to be associated with two rare diseases characterized by disorders of the joints, skeletal system, internal organs and motor development, and by developmental delay.

These three genes all code for (i.e. provide the cells with the instructions to build) proteins involved in lysosome function. The lysosome is a small body found inside animal cells that functions as a "garbage truck," or recycler, removing damaged molecules and even viruses from inside the cell. Without proper lysosome cleaning function, damage builds up inside the cell and interferes with proper cell function. Lysosomal diseases are rare, but well known.

The observed mutations in the three genes were found in 25 out of 786 stutterers (i.e. 3.2%), as opposed to only 4 out of 744 non-stutterers (i.e.0.54%). The team examined three of the stutterers with the variant genes, and none showed any evidence of the classic symptoms of the lysosomal disease cited above.

Research using mice has shown that two of these genes are expressed in the brain, in regions associated with emotion and motor function. All three genes are known to be expressed in many tissues in the body, and throughout life.

Summary: the genes found probably contribute to a small fraction of stuttering worldwide. The manner by which the proteins produced by these genes affect speech is unknown, but a search for a possible biological mechanism for the origin of stuttering in some cases can now be begun. Not all people who get these gene variants become stutterers, and only a small number of stutterers in this study have these gene variants. This condition is very common in such conditions, and is to be expected: stuttering is not a single, simple genetic trait. This study says nothing about possible non-genetic causes of stuttering, and does not rule out significant non-genetic influences on cases in which a genetic predisposition is present.

(Please note that Mark writes non-genetic influence and not environmental influence as many people and journalist write. Non-genetic does not imply a social influence like parental environment, but could be the results of random events within the body, random environmental events like being hit by a comet or virus, or/and systematic environmental influences like social environment (including parents, or peers) or physical (like weather).)


James said...


CNN have just published a video report about this breakthrough:

Ora said...

Mark - Do you consider this a "breakthrough"? It's an interesting result, certainly, but what does it break us through to?

Ka said...

I always thought that "stuttering genes" should be some genes expressed specifically in brain, or even in specific parts of brain. Then mutation of such genes would only result in disruption of some brain functions (speech).
But these lysosome-related genes function in many different tissues. Somehow mutations of these genes, in combination with other factors, lead to pathology only in parts of the brain responsible for speech, but not other parts of brain / body.

Kanstantsin said...

I think the real in genetics breakthrough will come soon. In next several years the technique called "full genome sequencing"
will become really affordable. Then we will be able to directly compare the chemical structure of
all 23000 human genes from, let's say, 100 PWS with all genes from 100 normal people. And we will get information of all mutations in all genes associated with stuttering. We just have to wait.

Tom Weidig said...

I agree with you Kanstantsin.

Mark B. said...

Ora - this is definitely a breakthrough. There are still people in the stuttering industrial complex insisting on a behavioral, non-organic origin of stuttering. For the first time, researchers will be able to ask a solid question - how the heck does a failure in a lysosomal transfer protein affect speech production? It's like wanting to find gold nuggets, but not knowing to look in river beds. Until now, stuttering was in a black box. We knew it was in there (the brain) somewhere, but we had no idea where to look at a biochemical, functional scale. New breakthroughs are still required, but that's for another day.

Mark B. said...


Genes can be turned on and off in different body tissues at different times in development, from the fertilized egg to the mature adult. There can also be different mutations of the same gene, resulting in products (often proteins) that show different results. In the case of the genes in this study, different mutations are already known to cause very serious diseases. The "stuttering variant" shows no such symptoms in other parts of the body.

Anonymous said...

Mark B. -

So does this gene discovery mean they have identified genes that are responsible for the production/infulencing/development of sound, syllable, whole word, and phrase repetitions in people? Is this what the word "stuttering" represents in the gene finding? Just wondering.

Mark B. said...


Yes, that's the idea. This kind of study looks at people with the trait - full-blown stuttering - as opposed to people without the trait. Then, they look for differences in the DNA between the two groups. If some DNA mutation in a gene "segregates" together with the trait (stuttering), more than you'd expect by random chance, then you suspect that the mutation causes the trait in some way.

So they found specific genes that differ between stutterers and non-stutterers. They also showed that the difference in DNA sequence would be expected to produce a real, biological effect - it's not a trivial difference. So the evidence looks good.