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Migeon was inspired by Mary F. Lyon, and began to study G6PD markers and X-inactivation. She researched differences in TSIX, showing that it is only transcribed in from an inactive X chromosome, as well as demonstrating that the female heterozygous for a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) are mosaic for two types of cells; which demonstrated normal and deficient HPRT levels. She was able to clone sections of the X chromosome in the 1980s. Migeon has argued that women have an advantage over men in coping with disease and the environment owing to X-inactivation. She was at a meeting Cold Spring Harbor Laboratory shortly after her work on X-inactivation was becoming mainstream, when a group of women researchers voiced their support for the study. Migeon describes women as genetic mosaics due to their two distinctly different kinds of cells.
In 1978 Migeon founded the Johns Hopkins University PhD program in human genetics, a program she directed until 1989. Migeon disagreed with Lawrence Summers' remarks about women scientists.
Migeon served on the editorial boards of Cancer Research and the Journal of Experimental Zoology.
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