Novel Y-Chromosome Long Non-Coding RNAs Expressed in Human Male CNS During Early Development

Martin M Johansson; Philipp Pottmeier; Pascalina Suciu; Tauseef Ahmad; Ammar Zaghlool; Jonatan Halvardson; Elisabeth Darj; Lars Feuk; Christiane Peuckert; Elena Jazin

doi:10.3389/fgene.2019.00891

Novel Y-Chromosome Long Non-Coding RNAs Expressed in Human Male CNS During Early Development

Front Genet. 2019 Sep 24:10:891. doi: 10.3389/fgene.2019.00891. eCollection 2019.

Authors

Affiliations

¹ Department of Organismal Biology, EBC, Uppsala University, Uppsala, Sweden.
² Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
³ Department of Women's and Children's Health, International Maternal and Child Health (IMCH), Uppsala University, Uppsala, Sweden.
⁴ Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.
⁵ Department of Molecular Biology, Stockholms University, Stockholm, Sweden.

Abstract

Global microarray gene expression analyses previously demonstrated differences in female and male embryos during neurodevelopment. In particular, before sexual maturation of the gonads, the differences seem to concentrate on the expression of genes encoded on the X- and Y-chromosomes. To investigate genome-wide differences in expression during this early developmental window, we combined high-resolution RNA sequencing with qPCR to analyze brain samples from human embryos during the first trimester of development. Our analysis was tailored for maximum sensitivity to discover Y-chromosome gene expression, but at the same time, it was underpowered to detect X-inactivation escapees. Using this approach, we found that 5 out of 13 expressed gametolog pairs showed unbalanced gene dosage, and as a consequence, a male-biased expression. In addition, we found six novel non-annotated long non-coding RNAs on the Y-chromosome with conserved expression patterns in newborn chimpanzee. The tissue specific and time-restricted expression of these long non-coding RNAs strongly suggests important functions during central nervous system development in human males.

Keywords: Pan troglodytes; RNA sequencing; X-chromosome; Y-chromosome; gene expression; human brain development; long non-coding RNA; sex differences.