The X and Y Chromosomes in Mammalian Development 
Turner Syndrome 
As mentioned earlier, embryos normally have 
two sex chromosomes. However, about 1-2 per- 
cent of all human embryos have only one. The 
vast majority of such XO embryos are lost to spon- 
taneous miscarriage, but a few survive. The sur- 
viving XO embryos develop as females with a par- 
ticular set of physical features known as Turner 
syndrome, which includes short stature, webbing 
of the neck, puffiness of the hands and feet, and 
failure of secondary sexual development. It had 
been postulated that Turner syndrome might be 
the result of having a single copy of one or more 
genes common to the X and Y chromosomes. 
Nothing was known as to the number or nature of 
these hypothetical Turner genes. 
We began to focus our attention on this dis- 
order when it was noticed that certain XY females 
exhibit the same anatomic abnormalities as XO 
females. A pivotal finding was that all such XY 
Turner females lacked a portion of the Y chromo- 
some. We postulated that the Y chromosomal de- 
letions in these individuals might encompass not 
only a sex-determining gene or genes but also a 
nearby Turner gene or genes. 
Pursuing this hunch, we discovered two candi- 
date Turner genes, one on the Y chromosome and 
one on the X chromosome. These genes, named 
RPS4Y2in<S. RPS4X, appear to encode slightly dif- 
ferent forms of a protein constituent of the ribo- 
some, a structure required for protein synthesis 
and vital to all cells. In embryos lacking a second 
RPS4 gene (i.e., having a single RPS4), the rate at 
which ribosomes are constructed maybe slowed, 
in turn reducing the embryo's capacity to synthe- 
size other proteins. We are currently testing the 
highly speculative hypothesis that such a reduc- 
tion in protein synthetic capacity is the cause 
of some of the physical features of Turner 
syndrome. 
An interesting analogy can be found in the fruit 
fly Drosophila melanogaster. There, deficien- 
cies in ribosomal protein genes are associated 
with a particular "syndrome" called the "Mi- 
nute" (pronounced mi-NUTE) phenotype, which 
includes reduced body size, diminished viability 
and fertility, and specific anatomic abnormali- 
ties. The Drosophila Minutes may serve as a use- 
ful model system in which to study effects of 
RPS4 gene dosage. We are also exploring poten- 
tial mouse models of Turner syndrome. 
The very existence of related but nonidentical 
ribosomal protein genes on the X and Y chromo- 
somes raises the possibility that the ribosomes of 
human males may differ slightly from those of 
females. Experiments still in their early stages 
suggest that this is the case. Thus the differences 
between the sexes may extend all the way down 
to the most fundamental and vital of intracellular 
machines! 
The Human Y Chromosome 
As mentioned above, we constructed a map of 
the human Y chromosome by characterizing natu- 
rally occurring deletions, such as those found in 
XY females and XX males. We are continuing to 
refine this map, which is useful not only in study- 
ing sex determination and Turner syndrome, but 
also in examining the role of Y chromosomal 
genes in other processes, including the develop- 
ment of certain cancers and the making of sperm. 
We recently set out to "clone" the human Y 
chromosome as a series of overlapping segments, 
each segment constituting about 1 percent of the 
chromosome. Such an ordered array of cloned 
segments should facilitate the process of locat- 
ing and characterizing all genes on the Y chromo- 
some. Our efforts to map and clone the Y chro- 
mosome are supported by a grant from the Na- 
tional Institutes of Health. 
314 
