A Higher Mutational Burden in Females Supports a “Female Protective Model” in Neurodevelopmental Disorders
作者： Sébastien Jacquemont , Bradley P. Coe , Micha Hersch , Michael H. Duyzend , Niklas Krumm
DOI: 10.1016/J.AJHG.2014.02.001
关键词:
摘要: Increased male prevalence has been repeatedly reported in several neurodevelopmental disorders (NDs), leading to the concept of a “female protective model.” We investigated molecular basis this sex-based difference liability and demonstrated an excess deleterious autosomal copy-number variants (CNVs) females compared males (odds ratio [OR] = 1.46, p 8 × 10−10) cohort 15,585 probands ascertained for NDs. In independent autism spectrum disorder (ASD) 762 families, we found 3-fold increase CNVs (p 7 × 10−4) private single-nucleotide (SNVs) female (OR 1.34, 0.03). also showed that deleteriousness SNVs was significantly higher 0.0006). A similar bias observed parents Deleterious (>400 kb) were maternally inherited more often (up 64%, 10−15) than small < 400 kb 1.45, 0.0003). ASD cohort, increased maternal transmission SNVs. Although mutational burden lower cognition, remained, even after adjustment those cognitive differences. These results strongly suggest have etiological unlinked rare on X chromosome. Carefully phenotyped genotyped cohorts will be required identifying symptoms, which show gender-specific burden.
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