Genome Organization and Function 



Robert K. Moyzis. Julie Meyne, and Robert Ratliff 



Life Sciences Division. Los Alamos National Laboratory, Los Alamos, NM 87543 



(5031 667-3912, FTS 843-3912 



The ultimate objective of this program is to determine the molecular mechanisms by 

 which higher organisms organize and express their genetic information. Applications of 

 these basic investigations will include the development of novel approaches for (a) 

 detecting of human genetic diseases and (b) measuring the effects of low-level ionizing 

 radiation and/or carcinogen exposure. A combination of biochemical, biophysical, and 

 recombinant DNA techniques is being used to identify, isolate, and determine the roles 

 of DNA sequences involved in long-range genomic order. Currently, major efforts are 

 focused on determining the organization and function of human repetitive DNA 

 sequences. Major findings in the last year included (a) the use of synthetic repetitive 

 DNA oligomers to target in situ hybridization to specific human chromosomes and (b) 

 the isolation of the human telomere. Future studies will be directed toward (a) the 

 further definition and isolation of "functional"" repetitive DNA regions and (b) the 

 cloning, in yeast artificial chromosome vectors, of human telomere adjacent DNA 

 fragments. Defining the mechanisms responsible for organizing the mammalian 

 genome, as well as determining the genetic and nonmutational alterations 

 accompanying abnormal phenotypic change, is important to identifying the effects of 

 environmental contaminants from energy-related technologies. Determining the genetic 

 variability in these mechanisms provides a rational basis for establishing thresholds for 

 toxic substance exposures, for making valid cross-species extrapolations, and, 

 ultimately, for identifying individuals at risk. 



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