Whole exome and genome sequencing technologies are expected to change the way medicine will be practised in future. Several research projects are being conducted worldwide using these technologies. The primary focus of our group is to apply the exome sequencing to some specific disease areas such as:
1) Intellectual and developmental disabilities (including autism)
2) Tourette Syndrome
3) Infantile Spasms
Our goal is to not only discover novel disease-causing genes but also to relate the mutations in known disease-causing genes to imaging and clinical phenotypes.
We have systematically collected whole exome sequencing, SNP genotyping and neuroimaging data (MRI and Diffusion Tensor imaging) in these patient populations. Some of these studies have already been published and others are in different stages of acquisition and analysis. Some of our recent publications using these technologies are:
1. Sundaram SK, Huq AHM, Sun Z, Wilson BJ, Yu W, Chugani HT. Whole exome sequencing identifies novel, nonsynonymous variants in a large pedigree with Tourette Syndrome or chronic tic disorder. Annals of Neurology. 2011 May;69(5):901-4.
2. Sundaram SK, Huq AHM, Wilson B, Chugani HT. Tourette syndrome is associated with recurrent exonic copy number variants. Neurology, 2010 May 18;74(20):1583-90. Epub 2010 Apr 28.
3. Sundaram SK, Kumar A, Makki MI, Behen ME, Chugani HT, Chugani, DC. Diffusion Tensor Imaging of Frontal Lobe in Autism Spectrum Disorder. Cerebral Cortex. 2008.
4. Jeong JW, Sundaram SK, Kumar A, Chugani DC, Chugani HT. Aberrant Diffusion and Geometric Properties in the Left Arcuate Fasciculus of Developmentally Delayed Children: A Diffusion Tensor Imaging Study. AJNR Am J Neuroradiol. 2010 Dec 23.
5. Kumar A, Sundaram SK, Sivaswamy L, Behen ME, Makki MI, Ager J, Janisse J, Chugani HT, Chugani DC. Alterations in Frontal Lobe Tracts and Corpus Callosum in Young Children with Autism Spectrum Disorder. Cerebral Cortex 2010 Sep;20(9):2103-13. Epub 2009 Dec 17.
6.Sundaram SK, Sivaswamy L, Makki MI, Behen ME, Chugani HT. Absence of arcuate fasciculus in children with global developmental delay of unknown etiology: a diffusion tensor imaging study. Journal of Pediatrics. Epub Oct 24, 2007. 152:250-255, 2008.
Except under rare circumstances such as classical Mendelian disorders, identifying genetic causes/risk factors of diseases is associated with significant uncertainties. Hence, integrating the genome sequence data with expression, imaging and clinical data will become very important to decrease these uncertainties and increase our confidence in correctly identifying the causes and clinically important risk factors.
We would appreciate any comments.