<qa>  What is the chromosome inactivation of the carrier females?We will investigate this hypothesis through two complimentary aims. In the Background and Significance section, we first present data on a 53-member pedigree segregating an X-linked recessive lethal defect that results in skewed X inactivation in the carrier females via secondary selection against those cells with the defective X chromosome active. We have characterized this deletion to be a 500 kb approximate deletion in distal Xq28. Moreover, the carrier females show a statistically significant increase in the frequency of spontaneous abortion as compared to non-deletion carrying relatives. Secondly, in the Preliminary Studies section, we present data from a population based case-control study wherein highly skewed X chromosome inactivation is significantly correlated with idiopathic recurrent spontaneous abortion. This protocol attempts to elucidate the mechanism underlying this association. 