a longitudinal twin study of skewed x chromosome-inactivation纵向的双胞胎研究x chromosome-inactivation倾斜.pdfVIP

A Longitudinal Twin Study of Skewed X Chromosome- Inactivation 1 1,2 1,2 2 1 Chloe Chung Yi Wong , Avshalom Caspi , Benjamin Williams , Renate Houts , Ian W. Craig , Jonathan Mill1* 1 MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London, United Kingdom, 2 Departments of Psychology and Neuroscience, Psychiatry and Behavioral Sciences, Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, United States of America Abstract X-chromosome inactivation (XCI) is a pivotal epigenetic mechanism involved in the dosage compensation of X-linked genes between males and females. In any given cell, the process of XCI in early female development is thought to be random across alleles and clonally maintained once established. Recent studies, however, suggest that XCI might not always be random and that skewed inactivation may become more prevalent with age. The factors influencing such XCI skewing and its changes over time are largely unknown. To elucidate the influence of stochastic, heritable and environmental factors in longitudinal changes in XCI, we examined X inactivation profiles in a sample of monozygotic (MZ) (n = 23) and dizygotic (DZ) (n = 22) female twin-pairs at ages 5 and 10 years. Compared to MZ twins who were highly concordant for allelic XCI ratios, DZ twins showed much lower levels of concordance. Whilst XCI patterns were moderately stable between ages 5 and 10 years, there was some drift over time with an increased prevalence of more extreme XCI skewing at age 10. To our knowledge, this study represents the earliest longitudinal assessment of skewed XCI patterns, and suggests that skewed XCI m