Professor, Department of Molecular and Human Genetics; Program in Cell & Molecular Biology

B.A., University of Virginia, 1978
Ph.D., Massachusetts Institute of Technology, 1984
Postdoc, National Institute for Neurological, Communicative Disorders and Stroke, NIH, 1985
Postdoc, Baylor College of Medicine, 1986

RESEARCH INTERESTS:

One of the most exciting recent developments in human genetics has been the identification of unstable trinucleotide repeats involved in high frequency mutations leading to more than one dozen genetic disorders, including myotonic dystrophy and Huntington's disease. With collaborators, Dr. Nelson described the first of these unstable DNA sequences, a CGG trinucleotide repeat in the FMR1 gene and responsible for the fragile X site and mental retardation found in people with Fragile X syndrome. This is the most common form of inherited mental retardation, with a frequency of ~1/2000 males in the general population. The mechanism by which this mutation leads to disease is through loss of function of the FMR1 gene product due to diminished expression resulting from aberrant methylation of the gene. Recent evidence suggests that the gene product of FMR1 interacts with complexes of RNA and ribosomes, implying a role in regulation of translation. Efforts in the Nelson group are focused on dissecting this pathway and understanding the development of DNA instability at this locus. Two additional fragile sites are found in the vicinity of the FMR1 gene on the X chromosome. The Nelson laboratory described one of these at the molecular level (FRAXF) and has identified a second gene involved in mental retardation expressed from the FRAXE fragile site (FMR2). Efforts to understand the function of FMR2 are underway.

The group has recently identified the gene defect in the X-linked disorder Incontinentia Pigmenti. This mutation is lethal in males, and leads to a spectrum of effects in females. Mutations are found in an essential modulator of NF-kB activity (NEMO), and the role of loss of function for this protein in the disease is under investigation.

The Nelson group has been involved in numerous aspects of the Human Genome Project, with key input into the mapping and sequencing of the human X chromosome, and participation in several other sequencing projects, from fly to Rhesus monkey. Dr. Nelson also has interest in the genetic contribution to common disorders such as cancer, and has investigated the potential role of common variants in genes involved in DNA repair in human disease.

SELECTED PUBLICATIONS:

1. Zhang J, Fang Z, Lee CC, Albrecht U, Oostra B, Nelson DL (2008). Members of the Fragile X protein family regulate mammalian circadian behavior. Am. J. Hum. Genet. 83: 43-52.

2. Sofola OA, Jin P, Botas J, Nelson DL (2007). Argonaute-2-dependent rescue of a Drosophila model of FXTAS by FRAXE premutation repeat. Hum. Mol. Genet. 16: 2326-2332.

3. Sofola OA, Jin P, Qin Y, Duan R, Liu H, de Haro M, Nelson DL, Botas J (2007). RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS. Neuron 55: 565-571.

4. Spencer CM, Serysheva E, Yuva-Paylor LA, Oostra BA, Nelson DL, Paylor, R (2006). Exaggerated behavioral phenotypes in Fmr1/Fxr2 double knockout mice reveal a functional genetic interaction between Fragile X-related proteins. Hum. Mol. Genet. 15: 1984-1994.

5. Ross MT, Grafham DV, Coffey AJ, Scherer S,… Nelson DL,… et al. (2005). The DNA sequence of the human X chromosome. Nature 434: 325-337.

6. Koekkoek SK, Yamaguchi K, Milojkovic BA, Dortland BR, Ruigrok TJ, Maex R, De Graaf W, Smit AE, VanderWerf F, Bakker CE, Willemsen R, Ikeda T, Kakizawa S, Onodera K, Nelson DL, Mientjes E, Joosten M, De Schutter E, Oostra BA, Ito M, De Zeeuw CI (2005). Deletion of FMR1 in Purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in Fragile X syndrome. Neuron 47: 339-352.

7. Mientjes EJ, Willemsen R, Kirkpatrick LL, Nieuwenhuizen IM, Hoogeveen-Westerveld M, Verweij M, Reis S, Bardoni B, Hoogeveen AT, Oostra BA, Nelson DL (2004). Fxr1 knockout mice show a striated muscle phenotype: Implications for Fxr1p function in vivo. Hum. Mol. Genet. 13: 1291-1302.

8. Morales J, Hiesinger PR, Schroeder AJ, Kume K, Verstreken P, Jackson FR, Nelson DL, Hassan BA (2002). Drosophila Fragile X protein, DFXR, regulates neuronal morphology and function in the brain. Neuron 34: 961-972.

9. Gu Y, McIlwain KA, Weeber EJ, Yamagata T, Xu B, Antalffy BA, Reye C, Yuva-Paylor L, Armstrong D, Zoghbi H, Sweatt D, Paylor R, Nelson DL (2002). Impaired conditioned fear and enhanced long-term potentiation in Fmr2 knockout mice. J. Neurosci. 22: 2753-2763.

For more publications, see listing on Pub Med.

CONTACT INFORMATION:

David L. Nelson, Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza
Houston, Texas 77030, U.S.A.
Mail Stop: BCM225

Phone: 713-798-4787
Fax: 713-798-1116
E-mail:

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