patients. As a result, Dr. Kunkel's group has elimi- 
nated 90% of the gene as harboring a point mutation 
that might cause the SMA phenotype. In addition, 
key recombinant individuals have been identified 
that place SMA mutations 5' to the MAP- 1 B dinucleo- 
tide repeat polymorphisms. 
In collaboration with Dr. Conrad Gilliam (Co- 
lumbia University), the laboratory has used the 
MAP- IB clone and a flanking genetic marker to 
screen YAC (yeast artificial chromosome) libraries. 
The distance between these markers is thought to be 
no more than 2,000 kb, and while the laboratory's 
YACs nearly cover this distance, they do not 
currently overlap. All of the reagents necessary to 
identify in these YACs possible genes that might be 
involved in SMA have been set up, including three 
new cDNA libraries from muscle, spinal cord, and 
brain, as well as a panel of SMA patient blots. The 
aim is to identify all possible coding sequences in 
the region and compare them with those from both 
SMA patients and normal individuals, in an attempt 
to identify the SMA gene. 
The next year is expected to reveal new dystro- 
phin-related proteins and what role, if any, they play 
in Duchenne muscular dystrophy and other neuro- 
muscular disorders. 
Dr. Kunkel is also Professor of Pediatrics and 
Genetics at Harvard Medical School. 
Articles 
Anderson, M.D.S., Kunkel, L.M., and Khurana, 
T.S. 1992. Dystrophin mRNA in lyophilized tissue 
[letter]. Nature 335:778. 
Beggs, A.H., Byers, T.J., Knoll, J.H.M., Boyce, 
F.M., Bruns, G.A.P., and Kunkel, L.M. 1992. 
Cloning and characterization of two human skele- 
tal muscle alpha-actinin genes located on chro- 
mosomes 1 and 11. / Biol Chem 267:9281- 
9288. 
Beggs, A.H., Neumann, P.E., Arahata, K., Arikawa, 
E., Nonaka, I., Anderson, M.D.S., and Kunkel, 
L.M. 1992. Possible influences on the expression 
of X chromosome-linked dystrophin abnormali- 
ties by heterozygosity for autosomal recessive 
Fukuyama congenital muscular dystrophy. Proc 
Natl Acad Sci USA 89:623-627. 
Beggs, A.H., Phillips, H.A., Kozman, H., MuUey, 
J.C., Wilton, S.D., Kunkel, L.M., and Laing, N.G. 
1992. A (CA)n repeat polymorphism for the hu- 
man skeletal muscle a-actinin gene ACTN2 and its 
localization on the linkage map of chromosome 1 . 
Genomics 13:1314-1315. 
Brzustowicz, L.M., Kleyn, P.W., Boyce, P.M., Lien, 
L.L., Monaco, A.P., Penchaszadeh, G.K., Das, K., 
Wang, C.H., Munsat, T.L., Ott, J., Kunkel, L.M., 
and Gilliam, T.C. 1992. Fine-mapping of the spi- 
nal muscular atrophy locus to a region flanked by 
MAPIB and D5S6. Genomics 13:991-998. 
Byers, T.J., Kunkel, L.M., and Watkins, S.C. 1991. 
The subcellular distribution of dystrophin in 
mouse skeletal, cardiac, and smooth muscle. / 
Cell Biol 115:411-421. 
Byers, T.J., Neumann, P.E., Beggs, A.H., and Kun- 
kel, L.M. 1992. ELISA quantitation of dystrophin 
for the diagnosis of Duchenne and Becker muscu- 
lar dystrophies. Neurology 42:570-576. 
Cartaud, A., Ludosky, M.A., Tome, F.M.S., Collin, H., 
Stetzkowski-Marden, F., Khurana, T.S., Kunkel, 
L.M., Fardeau, M., Changeux, J.P., and Cartaud, J. 
1992. Localization of dystrophin and dystrophin- 
related protein at the electromotor synapse and 
neuromuscular junction in Torpedo marmorata. 
Neuroscience 48:995-1003. 
Evans, M.I., Greb, A., Kunkel, L.M., Sacks, A.J., 
Johnson, M.P., Boehm, C, Kazazian, H.H., Jr., and 
Hoffman, E.P. 1991. In utero fetal muscle biopsy 
for the diagnosis of Duchenne muscular dys- 
trophy. Am f Obstet Gynecol 165:728-732. 
Khurana, T.S., Byers, T.J., Kunkel, L.M., Sancho, 
S., Tanji, K., and Miranda, A.F. 1991. Dystrophin 
detection in freeze-dried tissue. Lancet 338:448. 
Khurana, T.S., Watkins, S.C, Chafey, P., Chelly, J., 
Tome, F.M.S., Kaplan, J.C., and Kunkel, L.M. 
1991. Immunolocalization and developmental 
expression of DRP in skeletal muscle. Neuromus 
Dis 3:185-194. 
Laing, N.G., Majda, B.T., Akkari, P.A., Layton, M.G., 
MuUey, J.C., Phillips, H., Haan, E.A., White, S.J., 
Beggs, A.H., Kunkel, L.M., Groth, D.M., Boundy, 
K.L., Kneebone, C.S., Blumbergs, P.C., Wilton, 
S.D., Speer, M.C., and Kakulas, B.A. 1992. Assign- 
ment of a gene (NEMl) for autosomal dominant 
nemaline myopathy to chromosome 1 . Am J Hum 
Genet 50:576-585. 
Lien, L.L., Boyce, F.M., Kleyn, P., Brzustowicz, L.M., 
Menninger, J., Ward, D.C., Gilliam, T.C, and 
Kunkel, L.M. 1991 ■ Mapping of human microtu- 
bule-associated protein IB in proximity to the spi- 
nal muscular atrophy locus at 5ql3. Proc Natl 
Acad Sci USA 88:7873-7876. 
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