The Basic Biology of Aging at the University of Washington
Debbie Nickerson

Biosketch Information
Email: debnick@u.washington.edu

As our knowledge of the baseline reference sequence between genotype and phenotype increases, so will our need to define the level of natural variation in human populations. In this regard, single nucleotide substitutions and unique insertions and deletions are the most common form of sequence variation and disease-causing mutation in the human genome. We have focused our efforts on developing approaches to improve the sensitivity, accuracy, and speed of identifying and typing these potentially functional genomic variations. We have applied automated fluorescence-based sequencing to this problem and are developing new computer tools to automatically detect and analyze the functional relevance of DNA variations. We are also developing new approaches to type these variations in human populations once they are identified, in an effort to multiplex (perform many assays at a single time) and miniaturize these systems.

Current projects include identification of SNPs in genes and pathways that underlie inflammatory responses in humans, including the T-cell receptor beta locus, affecting cardiovascular disease, and the NIEHS Environmental Genome Project, focused on examining the relationships between environmental exposures, inter-individual sequence variation in human genes and disease risk in US populations. The current project that has perhaps the greatest relationship to aging is the study of sequence variation in Apolipoprotein E (APOE), a gene for which allelic variation is associated with substantially increased or decreased risk for Alzheimer's disease. We believe that with time, determination of sequence variation will have a great impact in the understanding of variation in human lifespan and age-related disease susceptibility.

Dr. Nickerson is Associate Professor of Genome Sciences and Adjunct Associate Professor of Bioengineering. She is internationally recognized for her leading role in the study of DNA sequence variability.

Selected Relevant Publications
Nickerson DA, Taylor SL, Weiss KM, Clark AG, Hutchinson RG, Stengård J, Salomaa V, Vartianinen E, Boerwinkle E, Sing CF. DNA sequence diversity in a 9.7 kb region of the human lipoprotein lipase gene. Nature Genet 19:233-240, 1998.

Dietrich WE, Weber JL, Nickerson DA, Kwok P-Y. Isolation and Analysis of DNA Polymorphisms. In: Genome Analysis, Vol. 4. Birren et al., eds., 1998. pp. 135-186.

Picoult-Newberg L, Ideker TE, Pohl MG, Taylor SL, Donaldson MA, Nickerson DA, Boyce-Jacino M. Mining SNPs from EST databases. Genome Res 9:167-174, 1999.

Rieder MJ, Taylor SL, Clark AG, Nickerson DA. Sequence diversity in the human angiotensin converting enzyme (ACE). Nature Genet 22:59-62, 1999.

Garg K, Green P, Nickerson DA. Identification of candidate single nucleotide polymorphisms (cSNPs) in 165 human genes using assembled expressed sequence tags. Genome Res 9:1087-1092, 1999.

Templeton AR, Clark AG, Weiss KM, Nickerson DA, Boerwinkle E, Sing CF. Recombinational and mutational hotspots within the human lipoprotein lipase gene. Am J Hum Genet 66:69-83, 2000.

Nickerson DA, Taylor SL, Fullerton SM, Weiss KM, Clark AG, Stengård J, Boerwinkle E, Sing CF. Sequence diversity and large-scale typing of SNPs in the human apolipoprotein e gene. Genome Res 10:1532-1545, 2000.

Zhu X, McKenzie CA, Forrester T, Nickerson DA, Broeckel U, Schunkert H, Doering A, Jacob HJ, Cooper RS, Rieder MJ. Localization of a small genomic region associated with elevated ACE. Am J Hum Genet 67:1144-1153, 2000.

Kruglyak L, Nickerson DA. Variation is the spice of life. Nature Genet 27:234-236, 2001.

Subrahmanyan L, Eberle M, Clark AG, Kruglyak L, Nickerson DA. Sequence variation and linkage disequilibrium in the human T cell receptor Beta (TCRB) locus. Am J Hum Genet 69:381-395, 2001.