Arthur Beaudet

Last updated
Arthur L. Beaudet
Born1942 (age 81–82)
Woonsocket, Rhode Island, U.S.
Alma mater College of the Holy Cross (BS)
Yale University (MD)
Awards William Allan Award (1997) [1]
Scientific career
Fields Molecular genetics
Institutions Baylor College of Medicine
Thesis Differences in RNA codon recognition as a function of cellular tRNA content  (1967)
Notable students Huda Zoghbi [2]

Arthur L. Beaudet (born 1942) is an American physician-scientist who is the Henry and Emma Meyer Professor of Molecular and Human Genetics at Baylor College of Medicine, where he was the chairman of the Department of Molecular and Human Genetics.

Contents

Beaudet was inducted into the Institute of Medicine in 1995, [3] the Society of Scholars in 2008, [4] and into the National Academy of Sciences in 2011. He was previously the president of the American Society of Human Genetics.

Early life and education

Beaudet was born in Woonsocket, Rhode Island. [5] He was educated at the College of the Holy Cross, where he received a Bachelor of Science (B.S.) in biology, magna cum laude , in 1963. He then earned a Doctor of Medicine (M.D.), cum laude, from Yale Medical School in 1967. [6]

Beaudet completed a residency in pediatrics at Johns Hopkins Hospital in 1969 and a postdoctoral fellowship at the National Institutes of Health two years later. After his NIH fellowship ended in 1971, Beaudet began his affiliation with Baylor. [5] He retired from Baylor in January 2020.

Research

Beaudet began his research in the 1960s with studies on protein synthesis. [1] In the 1970s, Beaudet et al. demonstrated mutations in cultured somatic cells; he has also conducted much research on inborn errors of metabolism, particularly urea cycle disorders. [7] In 1988, Beaudet's laboratory published a paper regarding the mechanism by which uniparental disomy might cause certain types of human genetic disease. [8] This paper proposed four mechanisms for uniparental disomy, each of which has since been shown to occur. [5] His group co-discovered that the UBE3A gene was inactivated as the cause of Angelman syndrome, [9] and that deletion of the snoRNAs likely contributes to the Prader-Willi phenotype. [10] In collaboration with Isis (now Ionis) Pharmaceuticals he demonstrated that oligonucleotides could be used to activate the paternal allele of Ube3a in the mouse as a possible therapeutic correction in Angelman syndrome. [11]

Beaudet has published research on the possible association between the deficiency of a carnitine biosynthesis gene and risk of autism in boys, [12] and has contended that some of these cases of autism may be preventable through carnitine supplementation. [13] Beaudet has also developed a test which enables doctors to detect whether or not a child was conceived as a result of incest without testing either parent. [14] [15] Beaudet has worked for over a decade trying to develop a commercial form of cell-based noninvasive prenatal testing using fetal cells in the mother’s blood during the first trimester. [16] [17]

Beaudet has been a principal investigator at the Howard Hughes Medical Institute. [18]

Related Research Articles

<span class="mw-page-title-main">Prader–Willi syndrome</span> Rare genetic disorder involving an imprinted genomic region

Prader–Willi syndrome (PWS) is a rare genetic disorder caused by a loss of function of specific genes on chromosome 15. In newborns, symptoms include weak muscles, poor feeding, and slow development. Beginning in childhood, those affected become constantly hungry, which often leads to obesity and type 2 diabetes. Mild to moderate intellectual impairment and behavioral problems are also typical of the disorder. Often, affected individuals have a narrow forehead, small hands and feet, short height, and light skin and hair. Most are unable to have children.

<span class="mw-page-title-main">Chromosome 15q partial deletion</span> Medical condition

Chromosome 15q partial deletion is a rare human genetic disorder, caused by a chromosomal aberration in which the long ("q") arm of one copy of chromosome 15 is deleted, or partially deleted. Like other chromosomal disorders, this increases the risk of birth defects, developmental delay and learning difficulties, however, the problems that can develop depend very much on what genetic material is missing. If the mother's copy of the chromosomal region 15q11-13 is deleted, Angelman syndrome (AS) can result. The sister syndrome Prader-Willi syndrome (PWS) can result if the father's copy of the chromosomal region 15q11-13 is deleted. The smallest observed region that can result in these syndromes when deleted is therefore called the PWS/AS critical region. In addition to deletions, uniparental disomy of chromosome 15 also gives rise to the same genetic disorders, indicating that genomic imprinting must occur in this region.

<span class="mw-page-title-main">Uniparental disomy</span> Inheritance of two copies of one parents chromosome

Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or of part of a chromosome, from one parent and no copy from the other. UPD can be the result of heterodisomy, in which a pair of non-identical chromosomes are inherited from one parent or isodisomy, in which a single chromosome from one parent is duplicated. Uniparental disomy may have clinical relevance for several reasons. For example, either isodisomy or heterodisomy can disrupt parent-specific genomic imprinting, resulting in imprinting disorders. Additionally, isodisomy leads to large blocks of homozygosity, which may lead to the uncovering of recessive genes, a similar phenomenon seen in inbred children of consanguineous partners.

<span class="mw-page-title-main">UBE3A</span> Protein-coding gene in Homo sapiens

Ubiquitin-protein ligase E3A (UBE3A) also known as E6AP ubiquitin-protein ligase (E6AP) is an enzyme that in humans is encoded by the UBE3A gene. This enzyme is involved in targeting proteins for degradation within cells.

<span class="mw-page-title-main">Chromosome 15</span> Human chromosome

Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 99.7 million base pairs and represents between 3% and 3.5% of the total DNA in cells. Chromosome 15 is an acrocentric chromosome, with a very small short arm, which contains few protein coding genes among its 19 million base pairs. It has a larger long arm that is gene rich, spanning about 83 million base pairs.

<span class="mw-page-title-main">Medical genetics</span> Medicine focused on hereditary disorders

Medical genetics is the branch of medicine that involves the diagnosis and management of hereditary disorders. Medical genetics differs from human genetics in that human genetics is a field of scientific research that may or may not apply to medicine, while medical genetics refers to the application of genetics to medical care. For example, research on the causes and inheritance of genetic disorders would be considered within both human genetics and medical genetics, while the diagnosis, management, and counselling people with genetic disorders would be considered part of medical genetics.

<span class="mw-page-title-main">Topotecan</span> Chemical compound

Topotecan, sold under the brand name Hycamtin among others, is a chemotherapeutic agent medication that is a topoisomerase inhibitor. It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. It is used in the form of its hydrochloride salt to treat ovarian cancer, lung cancer and other cancer types.

Trisomic rescue is a genetic phenomenon in which a fertilized ovum containing three copies of a chromosome loses one of these chromosomes to form a diploid chromosome complement. If both of the retained chromosomes come from the same parent, then uniparental disomy results. If the retained chromosomes come from different parents then there are no phenotypic or genotypic anomalies. The mechanism of trisomic rescue has been well confirmed in vivo, and alternative mechanisms that occur in trisomies are rare in comparison.

<span class="mw-page-title-main">GABRB3</span> Protein-coding gene in the species Homo sapiens

Gamma-aminobutyric acid receptor subunit beta-3 is a protein that in humans is encoded by the GABRB3 gene. It is located within the 15q12 region in the human genome and spans 250kb. This gene includes 10 exons within its coding region. Due to alternative splicing, the gene codes for many protein isoforms, all being subunits in the GABAA receptor, a ligand-gated ion channel. The beta-3 subunit is expressed at different levels within the cerebral cortex, hippocampus, cerebellum, thalamus, olivary body and piriform cortex of the brain at different points of development and maturity. GABRB3 deficiencies are implicated in many human neurodevelopmental disorders and syndromes such as Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. The effects of methaqualone and etomidate are mediated through GABBR3 positive allosteric modulation.

<span class="mw-page-title-main">Marcus Pembrey</span> British clinical geneticist

Marcus Edred Pembrey FMedSci is a British clinical geneticist with a research interest in non-Mendelian inheritance in humans. He is Emeritus Professor of Paediatric Genetics at UCL Great Ormond Street Institute of Child Health and Visiting Professor of Paediatric Genetics, University of Bristol. He featured in a 2005 'Horizon' program on BBC television called 'the Ghost in Your Genes'.

<span class="mw-page-title-main">Small nuclear ribonucleoprotein polypeptide N</span> Protein-coding gene in the species Homo sapiens

Small nuclear ribonucleoprotein-associated protein N is a protein that in humans is encoded by the SNRPN gene.

<span class="mw-page-title-main">Angelman syndrome</span> Genetic disorder caused by a mutation of chromosome 15

Angelman syndrome (AS) is a genetic disorder that mainly affects the nervous system. Symptoms include a small head and a specific facial appearance, severe intellectual disability, developmental disability, limited to no functional speech, balance and movement problems, seizures, and sleep problems. Children usually have a happy personality and have a particular interest in water. The symptoms generally become noticeable by one year of age.

Potocki–Lupski syndrome (PTLS), also known as dup(17)p11.2p11.2 syndrome, trisomy 17p11.2 or duplication 17p11.2 syndrome, is a contiguous gene syndrome involving the microduplication of band 11.2 on the short arm of human chromosome 17 (17p11.2). The duplication was first described as a case study in 1996. In 2000, the first study of the disease was released, and in 2007, enough patients had been gathered to complete a comprehensive study and give it a detailed clinical description. PTLS is named for two researchers involved in the latter phases, Drs. Lorraine Potocki and James R. Lupski of Baylor College of Medicine.

<span class="mw-page-title-main">Silver–Russell syndrome</span> Medical condition

Silver–Russell syndrome, also called Silver–Russell dwarfism, is a rare congenital growth disorder. In the United States it is usually referred to as Russell–Silver syndrome, and Silver–Russell syndrome elsewhere. It is one of 200 types of dwarfism and one of five types of primordial dwarfism.

<i>Ube3a-ATS</i> Non-coding RNA in humans

UBE3A-ATS/Ube3a-ATS (human/mouse), otherwise known as ubiquitin ligase E3A-ATS, is the name for the antisense DNA strand that is transcribed as part of a larger transcript called LNCAT at the Ube3a locus. The Ube3a locus is imprinted and in the central nervous system expressed only from the maternal allele. Silencing of Ube3a on the paternal allele is thought to occur through the Ube3a-ATS part of LNCAT, since non-coding antisense transcripts are often found at imprinted loci. The deletion and/or mutation of Ube3a on the maternal chromosome causes Angelman syndrome (AS) and Ube3a-ATS may prove to be an important aspect in finding a therapy for this disease. While in patients with AS the maternal Ube3a allele is inactive, the paternal allele is intact but epigenetically silenced. If unsilenced, the paternal allele could be a source of active Ube3a protein in AS patients. Therefore, understanding the mechanisms of how Ube3a-ATS might be involved in silencing the paternal Ube3a may lead to new therapies for AS. This possibility has been demonstrated by a recent study where the drug topotecan, administered to mice suffering from AS, activated expression of the paternal Ube3a gene by lowering the transcription of Ube3a-ATS.

Autism spectrum disorder (ASD) refers to a variety of conditions typically identified by challenges with social skills, communication, speech, and repetitive sensory-motor behaviors. The 11th International Classification of Diseases (ICD-11), released in January 2021, characterizes ASD by the associated deficits in the ability to initiate and sustain two-way social communication and restricted or repetitive behavior unusual for the individual's age or situation. Although linked with early childhood, the symptoms can appear later as well. Symptoms can be detected before the age of two and experienced practitioners can give a reliable diagnosis by that age. However, official diagnosis may not occur until much older, even well into adulthood. There is a large degree of variation in how much support a person with ASD needs in day-to-day life. This can be classified by a further diagnosis of ASD level 1, level 2, or level 3. Of these, ASD level 3 describes people requiring very substantial support and who experience more severe symptoms. ASD-related deficits in nonverbal and verbal social skills can result in impediments in personal, family, social, educational, and occupational situations. This disorder tends to have a strong correlation with genetics along with other factors. More research is identifying ways in which epigenetics is linked to autism. Epigenetics generally refers to the ways in which chromatin structure is altered to affect gene expression. Mechanisms such as cytosine regulation and post-translational modifications of histones. Of the 215 genes contributing, to some extent in ASD, 42 have been found to be involved in epigenetic modification of gene expression. Some examples of ASD signs are specific or repeated behaviors, enhanced sensitivity to materials, being upset by changes in routine, appearing to show reduced interest in others, avoiding eye contact and limitations in social situations, as well as verbal communication. When social interaction becomes more important, some whose condition might have been overlooked suffer social and other exclusion and are more likely to have coexisting mental and physical conditions. Long-term problems include difficulties in daily living such as managing schedules, hypersensitivities, initiating and sustaining relationships, and maintaining jobs.

Chromosomal deletion syndromes result from deletion of parts of chromosomes. Depending on the location, size, and whom the deletion is inherited from, there are a few known different variations of chromosome deletions. Chromosomal deletion syndromes typically involve larger deletions that are visible using karyotyping techniques. Smaller deletions result in Microdeletion syndrome, which are detected using fluorescence in situ hybridization (FISH)

<span class="mw-page-title-main">Microdeletion syndrome</span> Syndrome caused by chromosomal deletion

A microdeletion syndrome is a syndrome caused by a chromosomal deletion smaller than 5 million base pairs spanning several genes that is too small to be detected by conventional cytogenetic methods or high resolution karyotyping. Detection is done by fluorescence in situ hybridization (FISH). Larger chromosomal deletion syndromes are detectable using karyotyping techniques.

Intragenomic and intrauterine conflicts in humans arise between mothers and their offspring. Parental investment theory states that parents and their offspring will often be in conflict over the optimal amount of investment that the parent should provide. This is because the best interests of the parent do not always match the best interests of the offspring. Maternal-infant conflict is of interest due to the intensity of maternal investment in her offspring. In humans, mothers often invest years of care into their children due to the long developmental period before children become self-sufficient. 

Merlin G. Butler is an American physician scientist and professor at the University of Kansas Medical Center's Departments of Psychiatry & Behavioral Sciences and Pediatrics. He is board-certified in Clinical Genetics and Clinical Cytogenetics and was inducted into the American College of Medical Genetics and Genomics in 1993 as a founding fellow. He has over 500 publications in peer-reviewed journals, numerous book chapters.

References

  1. 1 2 Lupski, J. R. (2008). "Allan Award Introduction: Arthur L. Beaudet". The American Journal of Human Genetics. 82 (5): 1032–1033. doi:10.1016/j.ajhg.2008.04.011. PMC   2427270 . PMID   18610510.
  2. ↑ Researchers Toil With Genes on the Fringe of a Cure
  3. ↑ "Arthur L. Beaudet, M.D." Institute of Medicine . Archived from the original on 19 February 2014. Retrieved 19 February 2014.
  4. ↑ Society of Scholars Inducts New Members
  5. 1 2 3 Lupski, J. R. (2002). "Introduction of Arthur L. Beaudet, Harland Sanders Award Recipient". Genetics in Medicine. 4 (5): 396–398. doi: 10.1097/00125817-200209000-00012 . PMID   12394354.
  6. ↑ "Beaudet, Arthur". Pri-Med. Retrieved 2024-06-30.
  7. ↑ Arthur Beaudet Archived December 6, 2013, at the Wayback Machine
  8. ↑ Spence, J. E.; Perciaccante, R. G.; Greig, G. M.; Willard, H. F.; Ledbetter, D. H.; Hejtmancik, J. F.; Pollack, M. S.; O'Brien, W. E.; Beaudet, A. L. (1988). "Uniparental disomy as a mechanism for human genetic disease". American Journal of Human Genetics. 42 (2): 217–226. PMC   1715272 . PMID   2893543.
  9. ↑ Matsuura, T; Sutcliffe, JS; Fang, P; Galjaard, RJ; Jiang, YH; Benton, CS; Rommens, JM; Beaudet, AL (January 1997). "De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome". Nature Genetics. 15 (1): 74–7. doi:10.1038/ng0197-74. PMID   8988172. S2CID   22923869.
  10. ↑ Sahoo, T; del Gaudio, D; German, JR; Shinawi, M; Peters, SU; Person, RE; Garnica, A; Cheung, SW; Beaudet, AL (June 2008). "Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster". Nature Genetics. 40 (6): 719–21. doi:10.1038/ng.158. PMC   2705197 . PMID   18500341.
  11. ↑ Meng, L; Ward, AJ; Chun, S; Bennett, CF; Beaudet, AL; Rigo, F (19 February 2015). "Towards a therapy for Angelman syndrome by targeting a long non-coding RNA". Nature. 518 (7539): 409–12. Bibcode:2015Natur.518..409M. doi:10.1038/nature13975. PMC   4351819 . PMID   25470045.
  12. ↑ Celestino-Soper, P. B. S.; Violante, S.; Crawford, E. L.; Luo, R.; Lionel, A. C.; Delaby, E.; Cai, G.; Sadikovic, B.; Lee, K.; Lo, C.; Gao, K.; Person, R. E.; Moss, T. J.; German, J. R.; Huang, N.; Shinawi, M.; Treadwell-Deering, D.; Szatmari, P.; Roberts, W.; Fernandez, B.; Schroer, R. J.; Stevenson, R. E.; Buxbaum, J. D.; Betancur, C.; Scherer, S. W.; Sanders, S. J.; Geschwind, D. H.; Sutcliffe, J. S.; Hurles, M. E.; Wanders, R. J. A. (2012). "A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism". Proceedings of the National Academy of Sciences. 109 (21): 7974–7981. doi: 10.1073/pnas.1120210109 . PMC   3361440 . PMID   22566635.
  13. ↑ Beaudet, AL (August 2017). "Brain carnitine deficiency causes nonsyndromic autism with an extreme male bias: A hypothesis". BioEssays. 39 (8). doi: 10.1002/bies.201700012 . PMC   5642934 . PMID   28703319.
  14. ↑ Schaaf, C. P.; Scott, D. A.; Wiszniewska, J.; Beaudet, A. L. (2011). "Identification of incestuous parental relationships by SNP-based DNA microarrays". The Lancet. 377 (9765): 555–556. doi: 10.1016/S0140-6736(11)60201-8 . PMID   21315943. S2CID   31316085.
  15. ↑ Vergano, Dan (11 February 2011). "DNA tests could reveal unknown proof of incest". USA Today . Retrieved 19 February 2014.
  16. ↑ Bi, W; Breman, A; Shaw, CA; Stankiewicz, P; Gambin, T; Lu, X; Cheung, SW; Jackson, LG; Lupski, JR; Van den Veyver, IB; Beaudet, AL (January 2012). "Detection of ≥1Mb microdeletions and microduplications in a single cell using custom oligonucleotide arrays". Prenatal Diagnosis. 32 (1): 10–20. doi:10.1002/pd.2855. PMID   22470934. S2CID   43511221.
  17. ↑ Vossaert, L; Wang, Q; Salman, R; McCombs, AK; Patel, V; Qu, C; Mancini, MA; Edwards, DP; Malovannaya, A; Liu, P; Shaw, CA; Levy, B; Wapner, RJ; Bi, W; Breman, AM; Van den Veyver, IB; Beaudet, AL (5 December 2019). "Validation Studies for Single Circulating Trophoblast Genetic Testing as a Form of Noninvasive Prenatal Diagnosis". American Journal of Human Genetics. 105 (6): 1262–1273. doi: 10.1016/j.ajhg.2019.11.004 . PMC   6904821 . PMID   31785788.
  18. ↑ Institute of Medicine (US) Roundtable on Research and Development of Drugs, Biologics; Yaffe, Sumner (2000), "Biographies", Rational Therapeutics for Infants and Children: Workshop Summary, National Academies Press (US), retrieved 2024-06-30
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