gene is mapped to chromosome 7q. Extensive stud- 
ies of a North American population demonstrated 
strong hnkage disequilibrium with the markers KM- 
19 and XV-2c, such that individuals of the highest 
risk genotype are 80 times more likely to carry the 
CF mutation than individuals of the lowest risk ge- 
notype. The laboratory has described detailed 
methods for use of linkage disequilibrium for diag- 
nosis of genetic diseases, using CF as a model. The 
laboratory extended the application of the poly- 
merase chain reaction for rapid molecular analysis 
of samples for prenatal diagnosis and carrier detec- 
tion by establishing this method for polymorphisms 
detected by the KM- 19, XV-2c, and J3.ll probes. 
More recently the laboratory has analyzed hun- 
dreds of samples using direct detection of the most 
common mutation causing CF, in collaboration 
with Drs. Francis S. Collins (HHMI, University of 
Michigan Medical School) and Lap-Chee Tsui (To- 
ronto), who cloned the gene for CF. Direct analysis 
for the most common mutation identifies the defect 
in 70-75% of CF chromosomes, represents a major 
advance for prenatal diagnosis and carrier detec- 
tion, and makes it possible to begin population- 
based carrier screening for CF. 
IV Molecular Studies of Cell Adhesion Molecules. 
Numerous adhesion molecules on the surface of 
leukocytes and endothelial cells are being identi- 
PUBLICATIONS 
fied as the result of work in many different labora- 
tories. The leukocyte- integrin complex is a major 
cell adherence molecule on the surface of granulo- 
cytes and other leukocytes, and genetic defects in 
the P-subunit of this integrin cause human leuko- 
cyte adhesion deficiency, a fatal granulocyte dis- 
order. The mutation in one patient with leukocyte 
adhesion deficiency was identified as an ATG to 
AAG change in the initiation codon. A major goal of 
work in the laboratory is to develop mouse mu- 
tants for numerous leukocyte and endothelial 
cell adhesion molecules using homologous recom- 
bination in ES cells. Toward this end, the cDNA for 
the P-subunit of the murine leukocyte integrin and 
the cDNA for the murine intercellular adhesion 
molecule- 1 (ICAM-1) were cloned and sequenced. 
Murine genomic clones for both genes were iso- 
lated, and recombinant DNA constructs suitable for 
homologous recombination in ES cells are being 
prepared. It is expected that genetic variation in the 
leukocyte and endothelial cell adhesion molecules 
will be of major importance in the pathogenesis of 
inflammatory disorders and vascular disorders such 
as vasculitis and atherosclerosis. 
Dr. Beaudet is also Professor in the Institute for 
Molecular Genetics and the Departments of Pe- 
diatrics and of Cell Biology at Baylor College of 
Medicine. 
Books and Chapters of Books 
Beaudet, A.L., Scriver, C.R., Sly, WS., Valle, D., Cooper, D.N., McKusick, V.A., and Schmidke, J. 1989- Genetics 
and biochemistry of variant human phenotypes. In The Metabolic Basis of Inherited Disease (Scriver, C.R., 
Beaudet, A.L. , Sly WS., and VaUe, D. , Eds). New York: McGraw-Hill, pp 1-164. 
Beaudet, A.L., and Thomas, G.H. 1989. Disorders of glycoprotein degradation: mannosidosis, fucosidosis, 
sialidosis, and aspartylglycosaminuria. In The Metabolic Basis of Inherited Disease (Scriver, C.R., Beaudet, 
A.L. , Sly WS., and Valle, D. , Eds). New York: McGraw-HiU, pp 1603-1621. 
Boat, T.F., Welsh, M.J., and Beaudet, A.L. 1989. Cystic fibrosis. In The Metabolic Basis of Inherited Disease 
(Scriver, C.R., Beaudet, A.L. , Sly WS.,"and Valle, D. , Eds.). New York: McGraw-Hill, pp 2649-2680. 
Articles 
Ballantyne, CM., O'Brien, WE., and Beaudet, A.L. 1989. Nucleotide sequence of the cDNAfor murine inter- 
cellular adhesion molecule-1 (VCMA-V) . Nucleic Acids Res 17:5853. 
Beaudet, A.L. , Feldman, G.L., Fernbach, S.D., Bufifone, G.J., and O'Brien, WE. 1989- Linkage disequilibrium, 
cystic fibrosis, and genetic counseling. Am J Hum Genet 44-319-^26. 
Farrall, M., Wainwright, B.J., Feldman, G.L., Beaudet, A.L., Sretenovic, Z., Halley D., Simon, M., Dickerman, 
L., Devoto, M., Romeo, G., Kaplan, J. -C, Kitzis, A., and Williamson, R. 1988. Recombinations between IRP 
and cystic fibrosis. Am J Hum Genet 43:471-475. 
Continued 
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