David L. Nelson (born 1956) is an American human geneticist, currently an associate director at the Intellectual and Developmental Disabilities Research Center (1995), and professor at the Department of Molecular and Human Genetics at Baylor College of Medicine BCM since 1999. Since 2018, he is the director at the Cancer and Cell Biology Ph.D program, and the director of Integrative Molecular and Biomedical Sciences Ph.D since 2015 at BCM.[1][2]
Nelson joined the MIT Center for Cancer Research (CCR) group of David Housman at the Massachusetts Institute of Technology as a postdoctoral trainee (1986–1989). Nelson's work using introduced selectable genes expanded approaches to whole human genome mapping. From 1984 to 1985, in an intramural National Institutes of Health program at the laboratory of Robert Lazzarini, Nelson studied neuroscience and defined genes encoding neurofilament proteins. In 1986 he joined the C. Thomas Caskey laboratory at the Institute of Molecular Genetics, Baylor College of Medicine.[3]
Applying PCR, a technique that allows rapid gene mapping and isolation of specific chromosomal regions, Nelson et al. identified chromosomal locations of large fragments of the human X chromosome;[4] Nelson contributed to the human, mouse and fly reference sequences and was a co-discoverer of the mutation that causes Fragile X syndrome as an expansion of a trinucleotide repeat in the FMR1 gene.[5] Nelson's contributions have led to the description of Lowe syndrome,[6] and the identification of FMR2 for FRAXE syndrome.[7]
Nelson's molecular techniques led to the development of genome mapping and sequencing and discovery of disease genes, contributing efforts to map and sequence of the human X chromosome. He was a leader in genetic and genomic analyses across all species.[4][8][9][10]
With a group of international collaborators, Nelson's research group was able to identify a recurrent, homology-driven deletion in the NEMO gene in Incontinentia pigmenti (IP), an X-linked genetic disease.[11][12][13][14][15]
By studying humans, mice, flies and yeast Nelson's research group has characterized the origins of instability in the repeat, the consequences of "premutation" length expansions, and the function of FMR1 and related FXR1 and FXR2. Nelson and his research group have defined roles for FMR1 and paralogs in circadian rhythm, energy metabolism, neuronal stem cell development, and microRNA function. Their research results are being used in research to define the role of FMR1 in development and potential treatment for these diseases in adulthood.[19][20][21][22][23]
FXTAS individuals are cognitively unaffected until they reach their 60 or 70, when they show neural degeneration and nuclear inclusions during autopsy. Nelson's research group has used flies and mice to identify and characterize modifiers that showed that the CGG repeat is necessary and sufficient to affect mammalian neurons. Models developed by Nelson's research group have improved the understanding of mechanisms of this disease, including a role for RNA-binding functions such as TDP-43 and alterations in 5-Hydroxymethylcytosine.[24][25][26][27]
Nelson is a member of the Board of Directors of the American Society of Human Genetics, was its President in 2018, and served as Secretary from 2003 to 2009.
Nelson has served in many advisory boards and committees, including FRAXA Research Foundation Advisory Board (1999–present), National Fragile X Foundation Advisory Board (1999–present), March of Dimes Grants Review Board (2010–2015), Hungtinton Disease Society of America Steering Committee (1999–2010), United States NIH/NICHD Mental Retardation Review Committee (1998–2002), and US DOE Joint Genome Institute Advisory Board (1997–2000).
^ abVerkerk, Annemieke J.M.H.; Pieretti, Maura; Sutcliffe, James S.; Fu, Ying-Hui; Kuhl, Derek P.A.; Pizzuti, Antonio; Reiner, Orly; Richards, Stephen; Victoria, Maureen F.; Zhang, Fuping; Eussen, Bert E.; van Ommen, Gert-Jan B.; Blonden, Lau A.J.; Riggins, Gregory J.; Chastain, Jane L.; Kunst, Catherine B.; Galjaard, Hans; Thomas Caskey, C.; Nelson, David L.; Oostra, Ben A.; Warren, Stephen T. (May 1991). "Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome". Cell. 65 (5): 905–914. doi:10.1016/0092-8674(91)90397-H. PMID1710175. S2CID21463845.
^Attree, Olivier; Olivos, Isabelle M.; Okabe, Ichiro; Bailey, L. Charles; Nelson, David L.; Lewis, Richard A.; Mclnnes, Roderick R.; Nussbaum, Robert L. (July 1992). "The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase". Nature. 358 (6383): 239–242. Bibcode:1992Natur.358..239A. doi:10.1038/358239a0. PMID1321346. S2CID4246631.
^Gu, Yanghong; Shen, Ying; Gibbs, Richard A.; Nelson, David L. (May 1996). "Identification of FMR2, a novel gene associated with the FRAXE CCG repeat and CpG island". Nature Genetics. 13 (1): 109–113. doi:10.1038/ng0596-109. PMID8673086. S2CID6781698.
^Adams, Mark D., George L. Gabor Miklos, Angela Center, Robert D. C. Saunders, Susan E. Celniker, Robert A. Holt, Cheryl A. Evans, et al. 2000. "The Genome Sequence of Drosophila melanogaster". Science. 287 (5461): 2185–2195. DOI: https://doi.org/10.1126/science.287.5461.2185
^Ross, Mark T.; Grafham, Darren V.; Coffey, Alison J.; Scherer, Steven; McLay, Kirsten; Muzny, Donna; Platzer, Matthias; Howell, Gareth R.; Burrows, Christine; Bird, Christine P.; Frankish, Adam; Lovell, Frances L.; Howe, Kevin L.; Ashurst, Jennifer L.; Fulton, Robert S.; Sudbrak, Ralf; Wen, Gaiping; Jones, Matthew C.; Hurles, Matthew E.; Andrews, T. Daniel; Scott, Carol E.; Searle, Stephen; Ramser, Juliane; Whittaker, Adam; Deadman, Rebecca; Carter, Nigel P.; Hunt, Sarah E.; Chen, Rui; Cree, Andrew; et al. (March 2005). "The DNA sequence of the human X chromosome". Nature. 434 (7031): 325–337. Bibcode:2005Natur.434..325R. doi:10.1038/nature03440. PMC2665286. PMID15772651.
^Julia E. Parrish, Angela E. Scheuerle, Richard A. Lewis, Moise L. Levy, David L. Nelson (1996). Selection Against Mutant Alleles in Blood Leukocytes is a Consistent Feature in Incontinentia Pigmenti Type 2. Human Molecular Genetics, 5 (11):1777–1783. DOI: https://doi.org/10.1093/hmg/5.11.1777
^Smahi, Asmae; Courtois, G.; Vabres, P.; Yamaoka, S.; Heuertz, S.; Munnich, A.; Israël, A.; Heiss, Nina S.; Klauck, S. M.; Kioschis, P.; Wiemann, S.; Poustka, A.; Esposito, Teresa; Bardaro, T.; Gianfrancesco, F.; Ciccodicola, A.; d'Urso, M.; Woffendin, Hayley; Jakins, T.; Donnai, D.; Stewart, H.; Kenwrick, S. J.; Aradhya, Swaroop; Yamagata, T.; Levy, M.; Lewis, R. A.; Nelson, D. L. (May 2000). "Genomic rearrangement in NEMO impairs NF-κB activation and is a cause of incontinentia pigmenti". Nature. 405 (6785): 466–472. Bibcode:2000Natur.405..466T. doi:10.1038/35013114. PMID10839543. S2CID4416325.
^Swaroop Aradhya, Hayley Woffendin, Tracy Jakins, Tiziana Bardaro, Teresa Esposito, Asmae Smahi, Christine Shaw, Moise Levy, Arnold Munnich, Michele D’Urso, Richard A. Lewis, Sue Kenwrick, David L. Nelson (2001). A recurrent deletion in the ubiquitously expressed NEMO (IKK-γ) gene accounts for the vast majority of incontinentia pigmenti mutations, Human Molecular Genetics. 10(19):2171–2179, https://doi.org/10.1093/hmg/10.19.2171
^Swaroop Aradhya, Tiziana Bardaro, Petra Galgóczy, Takanori Yamagata, Teresa Esposito, Henry Patlan, Alfredo Ciccodicola, Arnold Munnich, Sue Kenwrick, Matthias Platzer, Michele D’Urso, David L. Nelson (2001). Multiple pathogenic and benign genomic rearrangements occur at a 35 kb duplication involving the NEMO and LAGE2 genes. Human Molecular Genetics 10(22):2557–2567. DOI: https://doi.org/10.1093/hmg/10.22.2557
^Pieretti, Maura; Zhang, Fuping; Fu, Ying-Hui; Warren, Stephen T.; Oostra, Ben A.; Caskey, C.Thomas; Nelson, David L. (August 1991). "Absence of expression of the FMR-1 gene in fragile X syndrome". Cell. 66 (4): 817–822. doi:10.1016/0092-8674(91)90125-I. PMID1878973. S2CID31455523.
^Fu, Ying-Hui; Kuhl, Derek P.A.; Pizzuti, Antonio; Pieretti, Maura; Sutcliffe, James S.; Richards, Stephen; Verkert, Annemieke J.M.H.; Holden, Jeanette J.A.; Fenwick, Raymond G.; Warren, Stephen T.; Oostra, Ben A.; Nelson, David L.; Caskey, C.Thomas (December 1991). "Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox". Cell. 67 (6): 1047–1058. doi:10.1016/0092-8674(91)90283-5. PMID1760838. S2CID21970859.
^Eichler, Evan E.; Holden, Jeanette J.A.; Popovich, Bradley W.; Reiss, Allan L.; Snow, Karen; Thibodeau, Stephen N.; Richards, C. Sue; Ward, Patricia A.; Nelson, David L. (September 1994). "Length of uninterrupted CGG repeats determines instability in the FMR1 gene". Nature Genetics. 8 (1): 88–94. doi:10.1038/ng0994-88. PMID7987398. S2CID20075057.
^Jin, Peng; Zarnescu, Daniela C; Ceman, Stephanie; Nakamoto, Mika; Mowrey, Julie; Jongens, Thomas A; Nelson, David L; Moses, Kevin; Warren, Stephen T (4 January 2004). "Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway". Nature Neuroscience. 7 (2): 113–117. doi:10.1038/nn1174. PMID14703574. S2CID1146182.