Introduction to the DOE 

 Human Genome Program 



The structural characterization of genes and the elucidation of their encoded 

 functions have become a cornerstone of modem health research, biology, and 

 biotechnology. A genome program is an organized effort to characterize all the 

 genetic material — DNA — of an organism. The human genome encodes 50.000 to 

 100.000 genes on its 24 distinct chromosomes, but only some 2000 genes are now 

 available for study in the forni of identified cloned DNAs. To accelerate effective 

 access to all human genes and eventually togenerate reference DNA sequences of the 

 chromosomes, the U.S. Department of Energy (DOE) began a Human Genome 

 Initiative in 1986. Intensive studies of the needs and promise of genomics research then 

 ensued. The value of a broad, supportive infrastructure for genomics has now been 

 recognized in the United States and abroad. Genome projects on several important 

 organisms are now planned or are progressing. Two federal agencies are now 

 supporting an expanded national human genome project, and the coordination of 

 human genome research has become international in scope. 



Sequencing Technologies 



Resonance ionization mass spectrometer. Investigators are 

 shown with the resonance ionization mass spectrometer that is 

 used to measure stable isotopes of a variety of elements that 

 are attached to DNA. Since 50 or more stable isotopes are 

 available for such DNA labeling, a multiplex procedure is 

 available in which either the single radioisotope or the four 

 fluorescent labels are replaced. When performing sequence 

 analysis by using four stable isotopes simultaneously on the 

 four dideoxynucleotide-terminated DNA fragments, the gel 

 lanes needed for electrophoresis can be reduced from the 

 usual four lanes to one lane. Many such elements can be used 

 simultaneously in the same electrophoresis lane since the 

 resonance ionization mass spectrometer will sort out the 

 elements and all their isotopes. Even greater multiplexing 

 would occur when Church probes are used to locate DNA 

 fragments, since all hybridization could be performed 

 simultaneously. Studies are under way to label DNA with a 

 variety of elements that have multiple stable isotopes and to 

 detect the DNA so labeled. These studies are being carried out 

 at the Oak Ridge National Laboratory in collaboration with 

 Atom Sciences. Inc., where this mass spectrometer has been 

 developed to its present state. (Photograph provided by Bruce 

 Jacobson, Oak Ridge National Laboratory, and Heinrich 

 Arlinghaus, Atom Sciences, Inc.) 



