Tracking Genes That Cause Human Disease 
localized by a collaborative group, which in- 
cludes our laboratory. It is now known to lie in a 
region near the tip of the short arm of chromo- 
some 4, within an interval of approximately 2 
million base pairs. Using yeast artificial chromo- 
some cloning, we have generated an overlapping 
set of genomic clones from this region and are 
utilizing a variety of novel technologies to search 
for candidate genes. 
A new project in our laboratory this year is an 
intense effort to identify the gene responsible for 
early onset breast cancer, which has recently 
been mapped by Mary-Claire King and her col- 
leagues (University of California, Berkeley) to 
chromosome 17. Using genetic linkage analysis 
in families, as well as the analysis of tumors, we 
are narrowing down the responsible interval. Sig- 
nificant portions of the candidate interval have 
now been cloned in yeast artificial chromosomes. 
Utilizing the relatively new technology of physi- 
cal microdissection of chromosomes, we have 
been able to produce many new markers in this 
region of the long arm of chromosome 17; thus 
the opportunity to identify a major gene contrib- 
uting to this common and devastating disease in 
Western society is now quite real. 
•■.»• 
Colocalization of neurofibromin (the normal protein product of the neurofibromatosis gene) 
and microtubules. The same rodent cell has been double-labeled and visualized by fluorescence 
microscopy. Red shows staining with an antibody directed against tubulin, the major component 
of cytoplasmic microtubules. Green shows staining of neurofibromin that appears to decorate the 
microtubules. 
Research of Paula Gregory, David Gutmann, and Francis Collins. 
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