Gholson J. Lyon
M.D., Weill Cornell Medical College, 2004
Ph.D., Rockefeller University, 2003
Human genetics, neuropsychiatric diseases, whole genome sequencing, ethics
The Lyon laboratory focuses on analyzing human genetic variation and its role in severe neuropsychiatric disorders. We do this by studying large pedigrees living in the same geographic location, where one can study the penetrance and segregation of variants in a similar environmental background and with fewer population stratification concerns. Toward this end, we collect pedigrees in Utah and elsewhere, and then utilize exome and whole genome sequencing to find mutations that segregate with syndromes in the pedigrees. We focus on the discovery of families with rare diseases and/or increased prevalence for syndromes such as Tourette Syndrome, ADHD, obsessive compulsive disorder (OCD), mental retardation, autism and schizophrenia. Proving the biological relevance for newly discovered mutations is the major problem, so having access to research participants and derived tissues will be critically important, hence the need to engage directly with families.
A second focus of the laboratory is to elaborate the mechanistic basis of a new rare disease that we described in 2011. This is the first human disease involving a defect in the N-terminal acetylation of proteins, a common (yet vastly understudied) modification of eukaryotic proteins carried out by N-terminal acetyltransferases (NATs). We are currently calling this new disease Ogden Syndrome, in honor of where the first family resides. We are using several different cellular model systems to better understand the disease pathophysiology and the basic processes of N-terminal acetylation.
Please visit Gholson's Lab home page.
Lyon, G.J., and Wang, K. Identifying disease mutations in genomic medicine settings: current challenges and how to accelerate progress. Genome Med. 2012. 4: 58.
Lyon, G.J. 2012. Personalized medicine: Bring clinical standards to human-genetics research. Nature 482: 300–301.
Lyon, G.J. 2011. Interview, Personal account of the discovery of a new disease using next-generation sequencing. Pharmacogenomics 12: 1519–1523.
Lyon, G.J. Jiang, T., Van Wijk, R., Wang, W., Bodily, P., Xing, J., Tian, L., Robison, L., Clement, M., Yang, L., Zhang, P., Liu, Y., Moore, B., Glessner, J., Elia, J., Reimherr, F., van Solinge, W., Yandell, M., Hakonarson, H., Wang, J., Johnson, W.E., Wei, Z. and Wang, K.. 2011. Exome Sequencing and Unrelated Findings in the context of Complex Disease Research: Ethical and Clinical Implications. Discov. Med . 12: 41–55.
Rope, A.F., Wang, K., Evjenth, R., Xing, J., Johnston, J.J., Swensen, J.J., Johnson, W.E., Moore, B., Huff, C.D., Bird, L.M., Carey, J.C., Opitz, J.M., Stevens, C.A, Jiang, T., Schank, C., Fain, H.D., Robison, R., Dalley, B., Chin, S., South, S.T., Pysher, T.J., Jorde, L.B., Hakonarson, H., Lillehaug, J.R., Biesecker, L.G., Yandell, M., Arnesen, T., and Lyon, G.J. 2011. Using VAAST to Identify an X-Linked Disorder Resulting in Lethality in Male Infants Due to N-Terminal Acetyltransferase Deficiency. American Journal of Human Genet. 89: 28–43.