A.H. M. Mahbubul Huq, M.D., Ph.D.
Department of Neurology
Wayne State University
Dr. Huq is the recipient of a Cure Autism Now 2003 Pilot Grant Award, Candidate Genes for Autism on Chromosome 7q. In addition he has published 5 scientific publications using the AGRE resource over the last 2 years.
This Interview was provided by AGRE's Research Liaison, Vlad Kustanovich, Ph.D. For more information contact Dr. Kustanovich at 888-8AUTISM or email him at firstname.lastname@example.org
Q: How did you get started in autism research?
A: I am a child neurologist, trained in clinical genetics as well as molecular genetics. The genetics of a complex trait such as autism is an intellectual challenge. As a clinician, I see many patients with autism and want to do something that will one day make a difference for them. Moreover, my colleagues at Wayne State are involved in autism research so I am in a good environment to do this work.
Q: How would you characterize your approach to the study of autism genetics?
A: The general approach is to look for candidate genes based on chromosomal location. We also use information (already known from other research) about genes associated with "other disorders", such as Fragile X and Tuberous Sclerosis. For example, 70% of patients with Tuberous Sclerosis have autistic features. The same pathway may be somehow involved in the development of autism. This allows us to make more educated guesses and improve the odds of locating specific autism genes. Genes of known identity are tested directly for association with autism.
Q: I notice that in a number of your papers you focus on chromosome 7q. Would you talk about why that is?
A: Chromosome 7q is one of the areas that has been replicated by most groups in almost every genome scan. The strength of the linkage varies, but almost everyone has found some evidence for linkage on 7q, so it naturally became a major focus of our work.
Q: Has access to the AGRE resource been helpful in your research?
A: In our autism research for three years, we have only been able to recruit about 60 families and most of these families have only one child with autism. Without the samples from AGRE we would not have been able to carry out our studies since 60 families would not have been adequate to reach any significant conclusions. Offering DNA samples from well characterized families is incredibly helpful and a very effective way of stimulating research.
Q: Based on the result of your work, what biological pathways or systems do you think are affected in autism?
A: We are interested in the inositol signaling pathway, it is one of the pathways that is involved in cell growth. This is the pathway that is disrupted in Tuberous Sclerosis. Because it is involved in neuronal development, it may be helpful in explaining macrocephaly and abnormal brain development in autism. This pathway is also involved in neurotransmitter action. Whenever a growth factor or a neurotransmitter combines with a receptor, there is a signal for a protein or enzyme inside the cell. Those proteins activate other proteins. Eventually they control cell movement, cell growth, and other actions. These pathways are involved in brain development, neurotransmitter action and growth. We looked at some of the genes in about 200 families and we have evidence that this pathway could play a role in autism. Scientists know that autism is a disorder of brain development and we are interested in how the genes influence this process. We are also studying other genes that affect brain development and neurotransmitter pathways.
Q: What do you see as the role of environmental factors in the development and progression of autism?
A: We are looking at the involvement of immunological genes. We have some interesting data that we have not published yet. If there is an immunological abnormality, it may affect brain development because some genes play a role in both the immune system and brain development. Genetic variation in the immune system may also affect how a developing brain responds to viral infection.
Q: In addition to the AGRE biomaterials, what data do you find useful in the AGRE database?
A: I think that the phenotypic (clinical) data is very, very important. The more phenotypic data there is, the more useful the resource will be. You can think about autism in two different ways. One way perhaps is that autism is a collection of syndromes. Maybe different families have [autism] with a distinct cause. Just like Fragile X or Tuberous Sclerosis. There may be other disorders that we have still not identified, that are a collection of syndromes.
If it is not a collection of syndromes, it may be multiple risk factors that interact, including genetic and non-genetic factors. Either way, there is probably a lot of heterogeneity. The phenotypic data may be one of the ways to divide the whole collection of families into distinct subsets in which particular genes are involved. We are using the phenotypic characteristics as a covariate. By controlling for that phenotypic characteristic we will see whether we can distinguish between different subgroups. Phenotypic data also allow us to do a quantitative and a more powerful analysis.
Q: Any additional comments for the contributors, the families and friends of AGRE and Cure Autism Now?
A: We are very thankful for your help and contribution. With your help, I believe we will one day be able to find the causes of autism and how this process can be stopped or modified. Our group's research represents very challenging and stimulating work and it has been made easier and more effective by the contribution of AGRE families.