1989-90 Research Highlights 



Tlie first research and development projects supported by the Human Genome 

 Initiative were pilot projects in the national laboratories and in academia. 

 Subsequent projects have been initiated after evaluation by special peer review 

 panels in 1988 and 1989. Abstracts of all current projects are included in this report and 

 are supplemented by research narratives from national laboratories and by special 

 reports in the Appendices. There have been numerous incremental contributions to the 

 resource and technology development, in addition to significant progress toward the 

 major goals. Some highlights of the total DOE program include: 



The construction of libraries made up of DNA clones with large-capacity phage/ 

 cosmids containing human DNA is progressing within the National Laboratory Gene 

 Library Project. These libraries will represent the 24 distinct chromosomes (one 

 chromosome representing each of the 22 autosome pairs plus the X and Y 

 chromosomes) and. even now, are an extremely valuable resource for physical mapping 

 projects. Libraries representing chromosomes 4, 5. 8. II, 17, 21 , and 22 are being 

 offered for evaluation and cooperative use in 1990. 



Physical Mapping 



Cross-protection against Not\ sites in E. coli. 



Physical map construction is more efficient when 

 large DNA fragments are utilized. The restriction 

 endonuclease Not I cleaves the sequence 5'- 

 GCGGCCGC-3'; however, If DNA is first 

 methylated at "^CGCG with M»FnuD II or M»eep I, 

 a subset of the Not I sites cannot be cleaved; the 

 specificity of Not I Is effectively doubled. Shown In 

 the figure is a pulsed-field gel of E. coli RRI 

 genomic DNA treated as follows. Lanes 2 and 5: 

 Methylated at '^CGCG by M»FnuD II, then cut with 

 Not I. Lane 3: Unmethylated. cut with Not I. 

 Lanes 4 and 6: Methylated at "^CGCG by M»eep I, 

 then cut with Not I. Lane 1: Bacteriophage lambda 

 concatemer ladder, molecular weight marker, 

 48,502 bp per step. (Photograph provided by 

 Michael McClelland, California Institute of 

 Biological Research.) 



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