Characterization of human mosaic Rett syndrome brain tissue by single-nucleus RNA sequencing.

ABSTRACT: In females with X-linked genetic disorders, wild-type and mutant cells coexist within brain tissue because of X-chromosome inactivation, posing challenges for interpreting the effects of X-linked mutant alleles on gene expression. We present a single-nucleus RNA sequencing approach that resolves mosaicism by using single-nucleotide polymorphisms in genes expressed in cis with the X-linked mutation to determine which nuclei express the mutant allele even when the mutant gene is not detected. This approach enables gene expression comparisons between mutant and wild-type cells within the same individual, eliminating variability introduced by comparisons to controls with different genetic backgrounds. We apply this approach to mosaic female mouse models and humans with Rett syndrome, an X-link

SUBMITTER: Renthal W 

PROVIDER: S-EPMC6261686 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature