Merlin G. Butler, M.D., Ph.D.

Director, Division of Research
ABMG Certified Clinical Geneticist and Clinical Cytogeneticist
Department of Psychiatry and Behavioral Sciences; Pediatrics

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

Research Focus

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., Lee, J., Manzardo, A.M., Gold, J.A., Kimonis, V., Miller, J.L. & Driscoll, D.J. (2015).  Growth charts for non-growth hormone treated Prader-Willi syndrome. Pediatrics 135:e126-135.

Butler, M.G., Hossain, W., Rafi, S.K., Stephan, D. & Manzardo, A.M. (2015). Whole exome sequencing in females with autism implicates novel and candidate genes. Int. J. Mol. Sci. 16:1312-1335.

Cox, D.M. & Butler, M.G. (2015). Distal partial trisomy 15q26 and partial monosomy 16p13.3 in a 36 year old male with clinical features of both chromosomal abnormalities.  Cytogenet. Genome Res. 145(1):29-34.

Butler, M.G., McGuire, A. & Manzardo, A.M. (2015). Clinically relevant known and candidate genes for obesity and their overlap with human infertility and reproduction. J. Assist. Reprod. Genet. 32:495-508.

Manzardo, A.M., McGuire, A. & Butler, M.G. (2015). Clinically relevant genetic biomarkers from the brain in alcoholism with representation on high resolution chromosome ideograms. Gene 560(2):184-194.

Cox, D.M. & Butler, M.G. (2015). A case of the 7p22.2 microduplication: Refinement of the critical chromosome region for 7p22 duplication syndrome.  J. Ped. Genet. 4:34-37.

 Butler, M.G., Wang, K., Marshall, J.D., Naggert, J.K., Rethmeyer, J.A., Gunewardena, S. & Manzardo, A.M. (2015). Coding and noncoding expression patterns associated with rare obesity-related disorders: Prader-Willi and Alstrom syndromes. Adv. Genomics Genet. 5:53-75.

Butler, M.G., Hossain, W., Driscoll, D.J. & Manzardo, A.M. (2015). Increased plasma chemokine levels in children with Prader-Willi syndrome. Am. J. Med. Genet. 167:563-571.

Cox, D.M. & Butler, M.G. (2015). The 15q11.2 BP1-BP2 microdeletion syndrome: A review. Int. J. Mol. Sci. 16:4068-4082.

Genovese, A. Cox, D. & Butler, M.G. (2015).  Partial deletion of chromosome 1p31.1 including only the neuronal growth regulator 1 gene in two siblings. J. Ped Genet. 4:23-28.

Last modified: Jun 29, 2017


Merlin G. Butler, M.D., Ph.D.
Director, Division of Research
ABMG Certified Clinical Geneticist and Clinical Cytogeneticist