cation of the Blast- 1 gene on chromosome 1 bands 
q21-q23 puts it near the CDl cluster of immuno- 
globulin superfamily genes, suggesting that they 
may be evolutionarily related. The gene for a tri- 
functional protein that catalyzes three consecutive 
steps in the interconversion of tetrahydrofolate de- 
rivatives was mapped to human chromosome 
I4q24. A second, more weakly hybridizing sequence 
was found on the short arm of the X chromosome. 
The function of this sequence is not known. The 
site on chromosome 14 is the expressed gene, con- 
sistent with previous studies of the expression of 
the enzyme in somatic cell hybrids. 
Cytochrome c oxidase (COX) is the terminal en- 
zyme of the respiratory chain and consists of at 
least 13 subunits, three of which are mitochondrial 
encoded and have catalytic activity. In addition, 10 
smaller nuclear-encoded subunits exist that show 
tissue-specific expression. Systematic chromosomal 
mapping of the nuclear subunit genes is being un- 
dertaken as cloned probes become available. So far, 
most of the cDNAs for small subunits hybridized to 
more than one chromosomal site, and the identifi- 
cation of the coding sequence has been difficult. 
Subunit VIII, however, was localized to a single site 
on the proximal long arm of chromosome 11, even 
though there are different isoforms in muscle and 
nonmuscle tissue. COX deficiency is associated with 
a variety of human encephalomyopathies. The clon- 
ing and mapping of nuclear COX genes should lead 
to a genetic dissection of this heterogenous group 
of disorders. 
Phosphorylase kinase (PHK), the enzyme that ac- 
tivates glycogen phosphorylases in muscle, liver, 
and other tissues, is composed of four different 
subunits. The largest subunits, a and P, have been 
cloned recently from rabbit muscle cDNA. Dr. 
Francke's laboratory has used these probes to map 
the gene in humans by rodent x human somatic 
cell hybrid panels as well as in situ chromosomal 
hybridization. Both genes were found to exist at 
single sites. The a-subunit gene is located on the 
proximal long arm of the X chromosome in region 
Xql2-ql3 near the locus for phosphoglycerate ki- 
nase (PGKl). X-linked mutations leading to PHK 
deficiency, known to exist in humans and mice, are 
likely to involve this locus. The PHK deficiency mu- 
tation Phk has been mapped near Pgk-1 on the 
mouse X chromosome. The P-subunit gene PHKB 
was mapped to chromosome 16 region ql2-ql3. 
This information should help when families with 
autosomally inherited PHK deficiency are studied 
for mutation at this locus. 
To facilitate the correlation of the physical chro- 
mosome map with the genetic linkage map, 
searches for restriction fragment length polymor- 
phisms (RFLPs) are carried out with clinically rele- 
vant probes. A common Sad polymorphism was 
found in the gene for the Ml subunit of ribonucle- 
otide reductase that was previously assigned to the 
distal short arm of chromosome 11. The gene en- 
coding the X-linked form of chronic granulomatous 
disease was found to be polymorphic with Nsil. 
This RFLP should be useful for linkage mapping of 
region Xp21.1. 
A human endogenous retroviral element related 
to the simian sarcoma-associated virus was used for 
chromosome mapping studies. One molecular 
clone was found to hybridize predominantly to a 
site on human chromosome 18q21 and to recog- 
nize two RFLPs. This probe adds a useful marker to 
the linkage map of chromosome 18. 
III. Molecular Genetic Studies of Muscular 
Dystrophy. 
Since dystrophin cDNAs and dystrophin-specific 
antibodies have been made available by Dr. Louis 
M. Kunkel (HHMI, Harvard Medical School) and his 
colleagues, the presence and expression of this 
gene has been studied in individuals afifected with 
early onset progressive muscular dystrophy. Dr. 
Francke's laboratory previously published the char- 
acterization of partial deletions of this gene, the ori- 
gin of the mutations, and the discovery of germline 
mosaics in both males and females. Recent research 
has focused on the identification of families with a 
clinical disorder similar to Duchenne muscular dys- 
trophy (DMD), in which the dystrophin gene is 
structurally normal and the dystrophin protein is 
expressed in normal size and abundance. Such fam- 
ilies came to the attention through involvement of 
an affected girl with a normal chromosome consti- 
tution. Genetic marker studies using RFLPs from 
the region containing the DMD gene on Xp have 
provided conclusive evidence that in two families 
this gene was not involved. In a third family the 
manifesting female was a heterozygote for the same 
partial DMD gene deletion present in her affected 
brother. In this case, nonrandom X inactivation can 
explain the findings. The existence of an autosomal 
recessive form of early onset progressive muscular 
dystrophy has previously been suggested. Recently 
a cDNA that is partially homologous to the 3' end 
of the dystrophin sequence has been found to map 
to human chromosome 6. This is now being tested 
Continued 
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