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Mutation on Y chromosome stops sperm production

December 1, 1999 - After an arduous search, Howard Hughes Medical Institute (HHMI) investigator David Page has found the first mutation on the Y chromosome that prevents sperm production and thus causes male infertility. The finding, described in the December issue of the journal Nature Genetics, may eventually help in the design of male contraceptives and treatments for infertile males.

"It's been very difficult to find the smoking gun - the definitive evidence that any particular gene is the cause of male infertility," said Page, whose laboratory is at the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology. "Of course this is only one case so we have certainly not solved a public health problem. But at least it's a first instance where we can provide an explanation."

Researchers have uncovered the genetic causes for a flood of diseases as more DNA data have become available. But the study of infertility has lagged. "The very idea that infertility could be genetic seemed not all that logical," said Page. "Most people didn't get beyond the idea of what genetics is - the study of disease passed on in families - and the definition of infertility - the inability to have families."

Genetics and infertility can coexist, however. The impact of an infertility mutation can be hidden, for example, depending on the identity of other genes present in an individual. Thus it is important to see if signs of male infertility, such as a low sperm count, coincide in related individuals such as brothers and uncles.

For now only about 20 percent of cases of male infertility can be traced either to the loss of a large chunk of the male Y chromosome, or to some other large chromosome abnormality, such as the presence of a second X chromosomes in a male. Normal males have an X and a Y chromosome, whereas females have two X chromosomes.

Page wanted to see which gene within one of the large missing Y chromosome chunks was
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Contact: Joseph Alper
alperj@hhmi.org
720-890-1956
Howard Hughes Medical Institute
29-Nov-1999


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