reversed in individuals with sickle cell anemia or 
thalassemia, their disease could be cured. The labo- 
ratory has been investigating DNA sequences in the 
promoter of the fetal globin gene in an effort to un- 
derstand this developmental switch. A series of 
seven nuclear protein factors that bind in a se- 
quence-specific manner to the promoter have been 
identified, and a number of these have been par- 
tially purified using affinity columns. The role of 
the transcription factor Spl in the -y-globin pro- 
moter has also been carefully investigated; Spl has 
been found to be responsible for much of the tran- 
scriptional activity associated with the CACCC se- 
quence, a control sequence common to nearly all 
globin genes. A different nuclear protein that binds 
to this CACCC sequence has recently been cloned 
and is under active investigation. Another approach 
is an evolutionary comparison of prosimian and pri- 
mate 7 promoter sequences, to address the ques- 
tion of how the 7-globin gene became recruited as a 
fetal gene, since it previously functioned in an em- 
bryonic pattern. Finally, the mutations identified in 
the 7 promoter that cause hereditary persistence of 
fetal hemoglobin are beginning to be understood; 
at least three of them show significant alterations in 
binding of one or more of the nuclear proteins 
identified, which suggests a mechanism for their 
phenotype. These studies should improve under- 
standing of the mechanism of fetal globin regula- 
tion and may lead to new ideas about therapy. 
Dr. Collins is also Associate Professor in the De- 
partments of Internal Medicine and Human Genet- 
ics at the University of Michigan Medical School. 
PUBLICATIONS 
Books and Chapters of Books 
Collins, F.S. 1988. Chromosome jumping. In Genome Analysis, A Practical Approach (Davies, K., Ed.). Lon- 
don: IRL Press, pp 73-94. 
Collins, F.S. , and Martin, J.B. 1989. Huntington's chorea. In 1989 yearbook of Science and Technology. New 
York: McGraw-Hill, pp 164-167. 
Prochownik, E.V, and Collins, F.S. 1989. cDNA and genomic cloning. In Methods of Hematology: Molecular 
Genetics (Benz, E., Ed.). New York: Churchill Livingstone, pp 72-87. 
Boehnke, M., Arnheim, N., Li, H., and Collins, F.S. 1989- Fine-structure genetic mapping of human chromo- 
somes using the polymerase chain reaction on single sperm: experimental design considerations. Am J 
Hum Genet 45:21-52. 
Collins, F.S., O'Connell, E, Ponder, B.A.J., and Seizinger, B.R. 1989. Progress towards identifying the neu- 
rofibromatosis (NFl) gene. Trends Genet 5:217-221. 
Collins, F.S., Ponder, B.A.J. , Seizinger, B.R., and Epstein, C.J. 1989. The von Recklinghausen neurofibromato- 
sis region on chromosome 17— genetic and physical maps come into focus. Am f Hum Genet 44:1-5. 
Diehl, S.R., Boehnke, M., Erickson, R.E, Ploughman, L.M., Seiler, K.A., Lieberman, J.L., Clarke, H.B., Bruce, 
M.A., Schorry, E.K., Pericak-Vance, M.A., O'Connell, P, and Collins, F.S. 1989. A refined genetic map of the 
region of chromosome 17 surrounding the von Recklinghausen neurofibromatosis (NFl) gene. Am J Hum 
Genet 44:33-37. 
Fountain, J.W, Lockwood, WK., and Collins, F.S. 1988. Transfection of primary human skin fibroblasts by 
electroporation. Gene 68:167-172. 
Fountain, J.W, Wallace, M.R. , Brereton, A.M., O'Connell, P , White, R.L. , Rich, D.C., Ledbetter, D.H., Leach, 
R.J., Fournier, R.E.K., Menon, A.G., Gusella, J.E, Barker, D., Stephens, K., and Collins, ES. 1989. Physical 
mapping of the von Recklinghausen neurofibromatosis region on chromosome 17. Am J Hum Genet 
44:58-67. 
Fountain, J.W, Wallace, M.R., Bruce, M.A., Seizinger, B.R., Menon, A., Gusella, J.F., Michels, VV, Schmidt, 
M.A., Dewald, G.W, and Collins, F.S. 1989. Physical mapping of a translocation breakpoint in neu- 
rofibromatosis. Science 244:1085-1087. 
Articles 
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