Archive | Stephen Scherer RSS feed for this section

Why are autistic people mainly male?

17 Sep

Excluding the ever humorous ideas of the Geier’s and more serious ideas of Simon Baron-Cohen regarding testosterone, the reasons as to why there are (or seem to be) many more autistic males than females have not been adequately explained. However that might be about to change.

A new study gives the first starting point as to why this situation might come about.

As we all know, males have an X and a Y chromosome whereas females have two X’s. This new study postulatesthat this fact plays an important role.

If a boy’s X-chromosome is missing the PTCHD1 gene or other nearby DNA sequences, they will be at high risk of developing ASD or intellectual disability. Girls are different in that, even if they are missing one PTCHD1 gene, by nature they always carry a second X-chromosome, shielding them from ASD…

The PTCHD1 gene is responsible for determining the development of human embryo’s and is already associated with autism. Because males only have 1 X chromosome, if this is defective then they – obviously – don’t carry that secondary level of shielding that females – with 2 X chromosomes – do.

However, this is very much preliminary. It should be noted that:

The researchers found that about one percent of boys with ASD had mutations in the patched domain containing 1 (PTCHD1) gene on the X-chromosome.

1% is not a very high number but as LBRB interviewee Stephen Scherer says:

The male gender bias in autism has intrigued us for years and now we have an indicator that starts to explain why this may be…

In other words, no one is saying this is a done deal – merely that its a strong possibility with some decent science behind it.

Interview with Stephen Scherer

11 Jun

Stephen Scherer is co-author on the recent paper ‘Functional impact of global rare copy number variation in autism spectrum disorders‘. I caught up with him via email to ask a few questions:

1) What is the ‘bottom line’ message readers can take away from your work?

I am always frustrated when I hear at the end of most news stories…’and we don’t know what can cause autism’. Data from the past few years including our new study show alterations in genes can cause autism. We have not found all of the genes yet, and not all autism cases can be accounted for (the genetics can be complex) but genes can cause autism. For the specialists, through our new study we show either de novo or rare inherited copy number variations as one form of genetic alteration involved in autism. The genes affected are often linked together in a connected functional pathway and may of these molecules dictate how brain cells (neurons) develop and communicate. Some of the autism genes we found have already been found to cause intellectual disabilities, which is not entirely surprising since many individuals with autism also have these challenges.

2) How does your paper tie in with other gene/autism studies?

We validate many previous findings, but also find dozens and dozens of new autism risk genes. Our data furthers the hypothesis that rare genetic alterations contribute much more relative risk to developing autism than common genetic variations.

3) What should future researchers use your study for in terms of direction to take their own work?

I think one of the most important impacts of the study is the design itself. Nature really wanted us to include the Figure 1, which outlines the design and analysis. CNV studies are still quite tricky to do and the data has to be of the highest quality to make sense of it. I think our study on autism will set the standard for all other studies going forward, so they should follow it. Moreover, many of the functional pathway studies published before may have been either underpowered, flawed by low resolution arrays or high false discovery rates, or incomplete study designs. We spent alot of time thinking of how to best do this properly so if others are interested they should read the Supplementary Information carefully. Use it as a guide. Finally, for the functional biologists look at the long list of genes we present in the Supplementary Information since they may find their favorite gene to be an autism candidate gene!

4) How difficult was it managing the input from such a very large amount of co-authors?

The Autism Genome Project has some 120 scientists from 11 countries involved (see the authorship list). We selected a ‘writing team’ comprised of genome scientists, statisticians, medical geneticists, psychiatrists and developmental pediatricians. Interesting, everyone saw their own story in the data. I pretty much new in advance what I wanted to see in the final manuscript so much of my job was bring focus to the many other good ideas (note that there are five other papers spinning out of this larger study presenting some of these other data and interpretations). In took about 12 solid months of analysis of the data, three months of writing and editing, alot of cursing, and then submission to Nature (with even more cursing). The review time from submission to publication took ~six months. This was the hardest for me (except other than constantly changing the author list….and affiliations). The reviewers were very very thorough and Nature can (rightfully) be very demanding. In the end we are very proud of the manuscript. Dalila Pinto who is the first author and a post-doc in the lab was the driving force behind the analysis and deserved a lions-share of the credit. Would I do it again? I’ve had two Senior Author papers in Nature this year, which have been very draining. But I would do it again!