Written by Dr. Peter Szatmari
The genetic study is ploughing full steam ahead. We now have about 200 families with two affected children. As you know, we have joined forces with the team at Hospital for Sick Children in Toronto and are working closely there with Dr. Steve Scherer (a molecular biologist), Dr. Andrew Paterson (a statistician) and Dr. Wendy Roberts (a developmental pediatrician). This allows us to include more families and to work with world experts on finding genes. Dr Scherer is a leading authority on chromosome 7 and many of you may know that chromosome 7 is the most likely spot that contains at least one of the autism genes.
In terms of our molecular work, we are going full steam ahead on chromosome 7 and have looked very closely at specific genes in that region. As well, we have tried to pinpoint the exact location of the autism gene. The results we get are promising but still much more work needs to be done. Even with the number of families we have, it still may not be enough and we have to work hard at recruiting more families into the study. Our plans are to complete a full genome scan (that is to look at all the chromosomes) within the next 4 years (if our funding from the Canadian Institutes of Health Research holds up).
We are also very interested in looking at “modifier genes”. These are genes that do not necessarily cause autism but may modify the severity of clinical expression. Modifier genes have been discovered for many other complex genetic disorders and may influence age of onset, severity and so on. It is possible that modifier genes exist in autism as well and account for why some children have Asperger syndrome, others PDDNOS and still others have autism. We know that these different subtypes share a common genetic origin but why some children from the same family have one type of PDD and another sibling has a different type is unknown. We have some promising leads on this topic and hopefully will have more to say at our next conference.
In the meantime, we continue to recruit families and draw blood. We are a bit low on blood from several families; in particular, some children with autism were difficult to obtain blood from but also some grand parents and parents. If we are to continue to look at different chromosomes and genes it is essential to have enough blood to extract the DNA we need. Before now we did not have funds to set up “cell lines”. We now plan to set up these cell lines which means we can grow cells from an individual to give us a perpetual supply of DNA (so we will not have to bother you again!). But for some people, we do not have enough blood that is frozen to grow these cell lines. As a result, in the next little while we will be contacting some of you to see if we can come to your house and draw a bit more blood. I hope you will consider this request seriously as it would be a great help to us to keep this project going. Solving the puzzle of the genetics of autism is going to be a long term proposition, it is turning out to be more difficult than originally anticipated. But I am confident that what we are learning now in terms of what genes do and how subgroups of children with autism differ will be essential steps towards reaching that elusive goal.
What else is happening in the genetics of autism?
There are now seven genome scans published in autism. A genome scan covers all the chromosomes to see if there are regions that contain autism genes. It represents an enormous amount of work; for example, most teams use about 400 genetic markers on all family members and most studies have at least 100 families involved. (That makes our study with about 200 families probably the largest in the world at this point). The results of these 7 studies are mixed. On the one hand, no study can say they have found a region where it is very likely there is an autism gene. The signals are weak all across the different chromosomes. On the other, the largest signals from several different studies overlap. That means that different groups are getting weak but interesting signals from the same region. That is very encouraging as it suggests that there are autism genes in those regions but they may account for only a subgroup of families or else they are genes of weak effect. The regions that contain
these overlapping signals are on chromosome 2, 7 and 13. The problem is that the regions identified are very large, they contain hundreds and hundreds of genes within them. The distance is too large to look gene by gene. So narrowing down the region by increasing sample size or looking at subgroups of children with autism is an important strategy. Once the regions are narrowed, researchers can see which genes in that region are likely candidates for autism (based on whether or not, for example, they are involved in brain development). One can sequence the genes directly to see if the sequence is different in children with autism compared to the general population. So all in all, we are much farther ahead than we were three years ago, but there is a lot more work to be done.
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