Merlin G. Butler, M.D., Ph.D., F.F.A.C.M.G

Director, Division of Research
Professor of Psychiatry, Behavioral Sciences and Pediatrics
Departments of Psychiatry & Behavioral Sciences and Pediatrics

M.D., University of Nebraska, 1978
Ph.D., Indiana University, 1984
Fellowship, Indiana University School of Medicine, 1980-1983

Genetics of obesity, autism and developmental disabilities; Prader-Willi syndrome.  Under the direction of Dr. Butler, the primary focus of the research program is understanding the cause and diagnosis of Prader-Willi syndrome (PWS), as the clinical genetic model of obesity and genomic imprinting, and for genotype-phenotype correlations by utilizing an NIH funded rare disease center for genetics and natural history studies in PWS and early onset morbid obesity.  PWS is the most commonly recognized cause of life-threatening obesity in children generally due to errors in genomic imprinting usually a 15q11-q13 chromosome deletion of paternal origin.  The 15q11-q13 region involves important genes for development of obesity, behavioral problems and autism. This research has led to the discovery of genomic imprinting and clinical differences in PWS subjects having either the larger typical type I or smaller type II chromosome 15q11-q13 deletion.  Greater maladaptive and abnormal behavioral scores are seen in those PWS subjects with the larger type I deletion and candidate genes identified.  Other obesity-related measures under study include body composition, energy balance, regional fat distribution, neuroimaging patterns and neuropeptides regulating eating behavior and comparison with PWS genetic subtypes. Furthermore, DNA, coding and non-coding RNA (microRNAs) studies are underway with targeted messenger RNAs from structural and regulatory genes involved in the pathogenesis of obesity, autism and neurodevelopment.  Analyzing and comparing coding and non-coding RNA patterns in individuals with Prader-Willi syndrome and those with simple obesity will allow for identification of disturbed obesity-related gene network pathways leading to potential treatment modalities applicable to the general population.  In collaboration with others, functional MRI scans and startle modulation responses in PWS and matched obese subjects using food picture stimulation paradigms during pre- and post-meal assessments are underway to better understand specific brain regions involved in eating behavior and satiation.  More recently, studies are underway to examine induced pluripotent stem cells in PWS and to characterize their cell biology which is required to learn more about pathophysiology and to develop potential therapeutic interventions.

Selected Publications

Butler, M.G., & Palmer, C.G.  (1983).  Parental origin of chromosome 15 deletion in Prader-Willi syndrome.  Lancet. 1285-1286.

Nicholls, R.D., Knoll, J.H.M., Butler, M.G., Karam, S., & Lalande, M.  (1989). Genetic imprinting suggested by maternal heterodisomy in non-deletion Prader-Willi syndrome.  Nature 342:281-285.

Mascari, M.J., Gottlieb, W., Rogan, P.K., Butler, M.G., Waller, D.A., Armour, J.A.L., Jeffreys, A.J., Ladda, R.L., & Nicholls, R.D.  (1992). The frequency of uniparental disomy in Prader-Willi syndrome.  New Engl. Journ. Med. 326:1599-1607.

Ohta, T., Gray, T., Rogan, P.K., Buiting, K., Gabriel, J.M., Saitoh, S., Muralidhar, B., Driscoll, D.J., Horsthemke, B., Butler, M.G., & Nicholls, R.D.  (1999). Imprinting mutation mechanisms in Prader-Willi syndrome represent a new paradigm for genetic disease.  Am. J. Hum. Genet. 64:397-413.

Butler, M.G., Bittel, D.C., Kibiryeva, N., Talebizadeh Z. & Thompson, T.  (2004).  Behavioral  differences among subjects with Prader-Willi syndrome and type I and type II deletions and maternal disomy.  Pediatrics 113: 565-574.

Talebizadeh, Z., Simon, S.D., & Butler, M.G.  (2006).  X chromosome gene expression in human tissues: Male and female comparisons.  Genomics 88:675-681.

Bittel, D.C., Kibiryeva, N., Sell, S.M., Strong, T.V., & Butler, M.G.  (2007).  Whole genome microarray analysis of gene expression in Prader-Willi syndrome.  Am. J. Med. Genet. A. 143:430-442.

Butler, M.G.  (2009).  Genomic imprinting disorders in humans: A mini-review. J. Assist. Reprod. Genet.9-10:477-486.

Bruce, A.S., Holsen, L.M., Chambers, R.J., Martin, L.E.,  Brooks, W.M., Zarcone, J.R., Butler, M.G., & Savage, C.R. (2010). Obese children show hyperactivation to food pictures in brain networks linked to motivation, reward, and cognitive control. Internat. J. Obes. (Lond). 34:1494-1500.

Burnside, R.D., Pasion, R., Mikhail, F.M., Carroll, A.J., Robin, N.H., Youngs, E., Gadi, I.K., Keitges, E., Jaswaney, V.L., Papenhausen, P.R., Potluri, R., Risheg, H., Smith, J.L., Schwartz, S., Tepperberg, J.H. & Butler, M.G.  (2011). Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2: A susceptibility region for neurological dysfunction including developmental and language delay. Hum. Genet. 130:517-528.

Butler, M.G.  (2011).  Prader-Willi syndrome: Obesity due to genomic imprinting. Curr. Genomics 12:203-223.

Butler, M.G. & Menitove, J.E.  (2011).  Umbilical cord blood banking: An update. J. Assist. Reprod. Genet.  28:669-676.

Last modified: Nov 16, 2012


Merlin G. Butler, M.D., Ph.D., F.F.A.C.M.G
Director, Division of Research
Professor of Psychiatry, Behavioral Sciences and Pediatrics