Current Research Interests:
Current research has focused primarily on the use of human mitochondrial DNA in forensic applications and disease diagnostics. In addition, we are developing Standard Reference Materials for improved mitochondrial DNA sequencing (SRM 2392 and SRM 2392-I), for detection of low-frequency heteroplasmic mutations (SRM 2394), and for accurate detection of the correct number of triplet repeats in Fragile X patients and their relatives (SRM 2399).
Our overall goal is to detect DNA damage and the chemical alterations of DNA bases following exposures to chemical (e.g., environmental toxicants) and physical (e.g., radiation) agents. In individuals with specific diseases, actual DNA base pair sequence changes have been observed in both mitochondrial and nuclear DNA. When all of the cells have the same altered genotype, these changes or mutations are fairly easy to determine using the polymerase chain reaction and sequencing. However, little research has been conducted to examine the mitochondrial DNA damage from environmental exposures or the specific mutations (actual base pair changes) that such exposures can cause. The need for this information comes from the knowledge that such mutations can lead to diseases including cancer. We are currently examining the low-frequency heteroplasmic single nucleotide polymorphisms (SNPs) and mutations found in mitochondrial DNA (especially those associated with diseases) and allele frequencies of SNPs in nucleic DNA of pooled samples from populations. The aim of this latter research project is to enable the screening of populations with and without specific diseases and to detect associated SNPs that may have a causal relationship with the disease. An interactive web site has been developed to allow investigators to search for information (e.g., what gene is affected, whether it causes an amino acid change, the nature of that change, the position in the protein, and the amino acid sequence of the new protein and if the change has been associated with a disease) on the mitochondrial mutations found in their samples (http://www.cstl.nist.gov/biotech/strbase/mitoanalyzer.html). In the area of homeland security, we have been trying to standardize the use of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) for the identification of bacteria.
Standard Reference Materials:
| SRM 2392-I: |
Mitochondrial Amplification and Sequencing Standard, 2003. Described in:
Levin, B.C., Holland, K.A., Hancock, D.K., Coble, M., Parsons, T.J., Kienker, L.J., Williams, D.W., Jones, MP, and Richie, K.L., “Comparison of the Complete mtDNA Genome Sequences of Human Cell Lines - HL-60 and GM10742A - from Individuals with Promyelocytic Leukemia and Leber Hereditary Optic Neuropathy, Respectively, and the Inclusion of HL-60 in the NIST Human Mitochondrial DNA Standard Reference Material - SRM 2392-I.” Mitochondrion 2:386-399 (2003).
Levin, B.C., Hancock, D.K., Holland, K.A., Cheng, H., and Richie, K.L. Human Mitochondrial DNA: Amplification and Sequencing Standard Reference Materials - SRM 2392 and SRM 2392-I. NIST SP 260-155. National Institute of Standards and Technology, Gaithersburg, MD (2003).
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| SRM 2392: |
Mitochondrial DNA Sequencing Standard, 1999. Described in:
Levin, B.C., Cheng, H., and Reeder, D.J., A Human Mitochondrial DNA Standard Reference Material for Quality Control in Forensic Identification, Medical Diagnosis, and Mutation Detection. Genomics 55:135-146 (1999).
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| SRM 1049: |
University of Pittsburgh Smoke Toxicity Method for Assessing the Acute Inhalation Toxicity of Combustion Products. Described in:
Levin, B.C., Alarie, Y., Stock, M.F., and Schiller, S.B., The Development of a Standard Reference Material for Calibration of the University of Pittsburgh Smoke Toxicity Method for Assessing the Acute Inhalation Toxicity of Combustion Products. J. Res. Natl. Inst. Stand. Technol. 97:245-252 (1992).
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| SRM 1048: |
Cup Furnace Smoke Toxicity Method for Assessing the Acute Inhalation Toxicity of Combustion Products. Described in:
Levin, B.C., Paabo, M., and Schiller, S. B., A Standard Reference Material for Calibration of the Cup Furnace Smoke Toxicity Method for Assessing the Acute Inhalation Toxicity of Combustion Products. J. Res. Natl. Inst. Stand. Technol. 96:741-755 (1991) |
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Representative Publications:
Kazumasa Sekiguchi, Kentaro Kasai and Barbara C. Levin, Intergenerational Transmission of a Human Mitochondrial DNA Heteroplasmy among Thirteen Maternally-Related Individuals and Differences between and within Tissues in Two Family Members. Mitochondrion 2:400-413 (2003).
Levin, B.C., Holland, K.A., Hancock, D.K., Coble, M., Parsons, T.J., Kienker, L.J., Williams, D.W., Jones, MP, and Richie, K.L., “Comparison of the Complete mtDNA Genome Sequences of Human Cell Lines - HL-60 and GM10742A - from Individuals with Promyelocytic Leukemia and Leber Hereditary Optic Neuropathy, Respectively, and the Inclusion of HL-60 in the NIST Human Mitochondrial DNA Standard Reference Material - SRM 2392-I.” Mitochondrion 2:386-399 (2003).
Benner, B.A. Jr., Goodpaster, J.V., DeGrasse, J.A., Tully, L.A., and Levin, B.C, “Characterization of Surface Organic Components of Human Hair by On-Line Supercritical Fluid Extraction - Gas Chromatography/Mass Spectrometry: A Feasibility Study and Comparison with Human Identification using Mitochondrial DNA Sequences.” J. Forensic Sciences 48:554-563 (2003).
Shin, M.G., Kajigaya, S., Levin, B.C., and Young, N.S., “Mitochondrial DNA Mutations in Patients with Myelodysplastic Syndromes.” Blood First Edition Paper, Prepublished online Nov. 21, 2002. Blood 101:3118-3125 (2003).
Hancock, D.K., Schwarz, F.P., Song, F., Wong, L-J.C., and Levin, B.C., “Design and Use of a Peptide Nucleic Acid for Detection of the Heteroplasmic Low-Frequency Mitochondrial Encephalomyopathy, lactic Acidosis, and Stroke-like Episodes (MELAS) Mutation in Human Mitochondrial DNA.” Clin. Chem.48:2155-2163 (2002).
Lee, M.S. and Levin, B.C. “MitoAnalyzer, a Computer Program and Interactive Web Site to Determine the Effects of Single Nucleotide Polymophsms and Mutations in Human Mitochondrial DNA.” Mitochondrion 1:321-326 (2002).
Levin, B. C., Cheng, H., Kline, M. C., Redman, J. W., and Richie, K. L., “A Review of the DNA Standard Reference Materials Developed by the National Institute of Standards and Technology.” Fresenius’ J. Anal. Chem. 370:213-219, 2001.
Levin, B. C., “Smoke and Combustion Products.” Patty’s Toxicology, Fifth Edition, Volume VIII, Chapter 108, ed. by Eula Bingham, Barbara Cohrssen and Charles H. Powell, John Wiley & Sons, Inc. New York, pp. 648-668, 2001.
Levin, B. C. and Reeder, D. J., “Reference Materials for DNA Analysis.” In “Reference Materials for Chemical Analysis - Certification, Availability and Proper Usage” ed. by M. Stoeppler, W. R. Wolf and P. J. Jenks, Wiley-VCH, Weinheim, New York, Chichester, brisbane, Singapore, Toronto. pp.160-170, 2000.
Tully, L. A. and Levin, B. C., “Human Mitochondrial Genetics.” Biotechnology and Genetic Engineering Reviews, Vol. 17. Ed. by S. E. Harding, U. Nottingham, Sutton, Bonington UK), Chapter 6, pp. 147 - 177, 2000.
Levin, B.C., Combustion Toxicology, Encyclopedia of Toxicology, Ed. by P. Wexler, Academic Press, New York, 1998, p. 360 – 374, 1998.
NRC Committee (B.C. Levin, member), “Fire- and Smoke Resistant Interior Materials for Commercial Transport Aircraft.” National Research Council, National Materials Advisory Board, Publication Number NMAB-477-1, Washington, DC: National Academy Press, 1995.
Babrauskas, V., Harris, R.H., Jr., Gann, R.G., Levin, B.C., Lee, B.T., Peacock, R.D., Paabo, M., Twilley, W., Yoklavich, M.F., and Clark, H.M., “Fire Hazard Comparison of Fire-Retarded and Non-Fire-Retarded Products.” Technomic Publishing Co., Lancaster, PA (1990).
NRC Committee (B.C. Levin, member), “Complex Mixtures: Methods for In Vivo Toxicity Testing.” National Research Council, National Academy Press, ISBN 0-309-03778-6, 375p. (1988).
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