James C. Mullikin, Ph.D.

Associate Investigator
Genome Technology Branch

B.S. Purdue University, 1982
M.S. Purdue University, 1984
Ph.D. Delft University of Technology, Holland, 1993

(301) 496-2416 (301) 480-0634 mullikin@nhgri.nih.gov		Building 50, Room 5318 50 South Drive, MSC 8004 Bethesda, MD 20892-8004
Selected Publications

I am involved in a number of bioinformatics projects, which include SNP detection, the Haplotype Map project and whole genome sequence assembly. I will expand my research into the areas of comparative genomics to identify functional elements in genomes; genomic duplication analysis; evolutionary variation analysis; and by working with others here at the National Institutes of Health (NIH) to become involved in identification of the genetic contributions to cancer and disease.

Single Nucleotide Polymorphisms (SNPs) occur at a rate of about one SNP per 1000 bases when comparing any two unrelated human DNA sequences. These variations are useful as markers across the genome for disease association studies. I have been involved in SNP discovery since the beginning of The SNP Consortium (TSC) project. A large fraction of publicly available SNPs are due to the efforts of TSC and subsequent SNP mining efforts using my program, ssahaSNP.

I am now involved with the Haplotype Map (HapMap) project, and am currently focusing on determining the number of SNPs needed for the first phase of this project. This has involved SNP discovery modeling to determine how many additional SNPs should be discovered by random shotgun sequencing vs. directed sequencing. Current models indicate that we will need about 3 million more SNPs - or about 6 million in total - which will be discovered using ssahaSNP from additional random whole genome shotgun-reads currently being generated by the large-scale sequencing centers. I also continue to improve ssahaSNP with the goal of generating more SNPs from existing data.

Comparative genomics is an exciting field of study which is receiving much attention, as reflected in the recent publications related to the mouse genome: Nature, December 5th, 2002 and Genome Research, January 2003. By comparing mouse and human genomes, much more of the genomic landscape is resolvable, i.e., regions of functional importance are better conserved by purifying selective pressures, thus these regions stand out from the bulk of the sequence not under these constraints. Vertebrate genomes that have been sequenced and used for comparative analysis include human (for intra species variability), rat, fugu and tetraodon. More genomes are in the process of sequence generation, which currently includes zebrafish, chimpanzee and chicken. Using a targeted approach, NISC has been sequencing tens of species specifically for comparative analysis.