We can contribute to the field because premature ovarian failure often is associated with inherited defects on the X chromosome. Schlessinger directs the School of Medicine's Center for Genetics in Medicine, which is mapping the X chromosome. Women have two X chromosomes. Although only one is active, defects in either can interfere with reproduction. Collaborators, including Antonino Forabosco, M.D., at the University of Modena in Italy, have found defects called translocations on X chromosomes in cell lines from women with premature ovarian failure.
Translocations occur when a piece of one chromosome breaks off and attaches to another chromosome.
The attachment sites are called breakpoints. Whereas many diseases are caused by breakpoints at set positions, premature ovarian failure apparently can result from a breakpoint at one of many sites in a relatively large region of the X chromosome. So rather than disrupting a specific gene, such a breakpoint may prevent the X chromosome from pairing with its partner during the cell divisions that lead to egg production. As cells containing the YACs divide, the human DNA is copied over and over again, becoming abundant enough for mapping. The maps can be overlapped to determine the linear arrangement of genes and other features on the chromosome being studied.