Dorrance Rare Childhood Center Transcriptomic and Genomic Studies For Known and Unknown Genetic Etiology

This study of DNA and RNA sequencing of 5 parent-offspring trios is a single center study. The goal of this study is to characterize X chromosome inactivation (XCI) ratio in females using phased genomic variations obtained through whole genome or exome sequencing in trios, followed by allele-specific expression analysis of the phased, heterozygous alleles in the mRNA of the female offspring, and to apply this method to clinical diagnosis. The distribution of allele ratios across X obtained from mRNA sequencing allows for the estimation of X inactivation status of inherited X chromosomes, and the parameters of each parental allele distributions in the offspring''s mRNA data can be used as determinants for XCI ratio. This approach was used to evaluate the contribution of skewed XCI ratio to phenotypic heterogeneity in an undiagnosed, mild neurological condition.