Arthur L. Beaudet, M.D.
Henry and Emma Meyer Chair in Molecular Genetics and Professor, Department of Molecular and Human Genetics
Other Positions
Professor, Departments of Pediatrics and Molecular & Cellular Biology; Program in Cell & Molecular Biology
Education
B.S., College of the Holy Cross, 1963
M.D., Yale University School of Medicine, 1967
Resident, Pediatrics, John Hopkins Hospital, 1969
Postdoc, National Institutes of Health, 1971
Board Certifications
National Board of Medical Examiners
American Board of Pediatrics
American Board of Medical Genetics: Biochemical Genetics, Clinical Genetics, and Clinical Molecular Genetics
Professional Organizations
Member, Institute of Medicine of the National Academy of Sciences
Past President, American Society Human Genetics
Clinical Interests
Genetic and epigenetic causes of autism; Prader-Willi and Angelman syndrome; genetic diagnosis using array CGH; gene therapy for cystic fibrosis, Crigler-Najjar, and hemophilia
Research Interests
Our laboratory is studying the role of epigenetics and de novo mutations in human disease with particular emphasis on genomic imprinting and its role in Prader-Willi syndrome (PWS), Angelman syndrome (AS), and autism. Genomic imprinting is the phenomenon of differential expression of the two alleles at an autosomal locus based on their parent of origin; usually one allele is expressed and the other silenced. PWS and AS are distinct human disorders characterized by neurobehavioral abnormalities and mental retardation. They are caused by deficiency of paternally (PWS) or maternally (AS) expressed genes within chromosome 15q11-q13.
Our laboratory has contributed to identification of molecular defects causing PWS and AS, identified the UBE3A locus encoding E6-AP ubiquitin-protein ligase as the AS gene, and made numerous mouse models related to PWS and AS. The molecular findings in PWS and AS and evidence that genomic imprinting of 15q11-q13 also plays a role in autism have led us to propose a mixed epigenetic and genetic and mixed de novo and inherited (MEGDI) model for oligogenic inheritance of autism. This proposes a radically different model with recent or new mutations in one or a few major genes causing autism in any one individual. This is in contrast to the widely held hypothesis that many genes with ancient mutations cause autism through a multilocus epistasis model.
The lab is also focused on the use of array comparative genomic hybridization (aCGH) to detect novel mutations causing mental retardation (MR), autism, and schizophrenia. Recent results suggest that deletions of chromosome 15q13 cause a phenotype of MR, autism, schizophrenia, aggression, and violence. Examples of current projects are 1) unraveling the epigenetic and genetic basis of autism; 2) identifying the function of the HBII-85 snoRNAs whose deficiency causes PWS; 3) studying the role of deletions of chromosome 15q13 and other regions in aggression and violence; 4) identifying specific genes in 15q13 contributing to the deletion phenotype; and 5) developing a one million oligonucleotide array to determine copy number for all exons in the genome.
In collaboration with Dr. Philip Ng and Nicola Brunetti-Pierri, we are participating in preclinical studies of helper-dependent adenoviral (HD-Ad) vectors with the goal of initiating gene therapy clinical trials for hepatic delivery in hemophilia and for airway delivery in cystic fibrosis.
Selected Publications
- Dindot SV, Person R, Strivens M, Garcia R, Beaudet AL (2009). Epigenetic profiling at mouse imprinted gene clusters reveals novel epigenetic and genetic features at differentially methylated regions. Genome Res. 19(8): 1374-83. [Pub Med]
- Ben-Shachar S, Lanpher B, German JR, M Qasaymeh M, Potocki L, Nagamani SC, Franco LM, Malphrus A, Bottenfield GW, Spence JE, Amato S, Rousseau JA, Moghaddam B, Skinner C, Skinner SA, Bernes S, Armstrong N, Shinawi M, Stankiewicz P, Patel A, Cheung SW, Lupski JR, Beaudet AL, Sahoo T (2009). Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders. J. Med. Genet. 46(6): 382-8. [Pub Med]
- Brunetti-Pierri N, Stapleton GE, Law M, Breinholt J, Palmer DJ, Zuo Y, Grove NC, Finegold MJ, Rice K, Beaudet AL, Mullins CE, Ng P (2009). Efficient, long-term hepatic gene transfer using clinically relevant HDAd doses by balloon occlusion catheter delivery in nonhuman primates. Mol. Ther. 17(2): 327-33. [Pub Med]
- Sahoo T, del Gaudio D, German JR, Shinawi M, Peters SU, Person RE, Garnica A, Cheung SW, Beaudet AL (2008). Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster. Nat. Genet. 40(6): 719-21. [Pub Med]
- Beaudet AL, Belmont JW (2008). Array-based DNA diagnostics: let the revolution begin. Annu. Rev. Med. 59: 113-29. [Pub Med]
- Dindot SV, Antalffy BA, Bhattacharjee MB, Beaudet AL (2008). The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology. Hum. Mol. Genet. 17(1): 111-8. [Pub Med]
Awards and Honors
2007: Appointed, NIH Gene Therapy Resource Program Scientific Review Board
2007: Recipient, The American Society of Human Genetics Allen Award, October 2007
2002: Colonel Harland Sanders Award for Lifetime Achievement in Genetic Research and Education, March of Dimes
2001: The Dr. Claudia Benton Award for Scientific Research, Angelman Syndrome Foundation
2001: Baylor Medical Alumni Association Distinguished Faculty Award, 2001
1999: Michael E. DeBakey Excellence in Research Award
1999: Texas Genetics Society Barbara H. Bowman Award
1996-present: Henry and Emma Meyer Professor
Contact Information
Arthur L. Beaudet, M.D.
Henry and Emma Meyer Professor and Chair
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, MS BCM225
Houston, TX, 77030, U.S.A.
Phone: 713-798-4795
Fax: 713-798-7773
E-mail: