University of Washington
225 Fluke Hall
Genome Center, Box 352145
Seattle, WA 98195-2145
Phone: (206) 616-8425
FAX: (206) 616-5242
Dr. Kaul’s research interests span protein chemistry and enzymology, characterization of human genetic disorders, and application and development of high throughput technologies in genomics. He is the scientific coordinator of the University of Washington Genome Center. His laboratory was responsible for elucidation of the molecular basis of aspartoacylase deficiency in the neurodegenerative disorder Canavan disease. Aspartoacylase specifically hydrolyses the aspartate derivative N-acetyl aspartic acid, a compound synthesized exclusively in the brain, as compared to wide expression of the aspartoacylase gene in various other tissues and cell types.
Canavan disease is prevalent among people of Ashkenazi Jewish descent, although patients from other populations have also been diagnosed with it. Dr. Kaul’s laboratory determined that the E285>A missense mutation accounted for 85%, and the Y231>X nonsense mutation accounted for over 13% of the mutations among patients of Ashkenazi descent. These two are the only known mutations among Ashkenazi Jewish patients. A single A305>E missense mutation was determined to account for almost half of the mutant chromosomes from patients of West European descent. Fifteen additional mutations described in patients of non-Jewish background were either infrequent or private in nature. The loss-of-function phenotype for individual mutations was validated by in vitro expression analysis. It was also determined that the carrier frequency of two common Canavan alleles among Ashkenazi Jewish people was 1:38. Following these findings, Canavan disease was added to the panel of the most common diseases among Ashkenazi Jews, and this population is now routinely screened for this disease.
Dr. Kaul’s current research interests include large-scale DNA sequencing, and he has finished a significant fraction of the human genome and several microbial genomes. He is involved in developing novel technologies for understanding the genetic variations that underlie the phenotypic differences in members of any population. The goal is to carry out Mb range resequencing of targeted regions in genomes from multiple individuals and thereby address basic and clinically relevant biological questions.
Investigator: Dr. Kaul is a Research Associate Professor of Medicine (Medical Genetics).