Expression of Random Sequences and de novo Evolved Genes From the Mouse in Human Cells Reveals Functional Diversity and Specificity.

Proteins that emerge de novo from noncoding DNA could negatively or positively influence cellular physiology in the sense of providing a possible adaptive advantage. Here, we employ two approaches to study such effects in a human cell line by expressing random sequences and mouse de novo genes that lack homologs in the human genome. We show that both approaches lead to differential growth effects of the cell clones dependent on the sequences they express.

Optical genome mapping of structural variants in Parkinson's disease-related induced pluripotent stem cells.

Background: Certain structural variants (SVs) including large-scale genetic copy number variants, as well as copy number-neutral inversions and translocations may not all be resolved by chromosome karyotype studies. The identification of genetic risk factors for Parkinson's disease (PD) has been primarily focused on the gene-disruptive single nucleotide variants. In contrast, larger SVs, which may significantly influence human phenotypes, have been largely underexplored.

Full-length RNA transcript sequencing traces brain isoform diversity in house mouse natural populations.

The ability to generate multiple RNA transcript isoforms from the same gene is a general phenomenon in eukaryotes. However, the complexity and diversity of alternative isoforms in natural populations remain largely unexplored. Using a newly developed full-length transcript enrichment protocol with 5' CAP selection, we sequenced full-length RNA transcripts of 48 individuals from outbred populations and subspecies of , and from the closely related sister species and as outgroups.

Gain-of-function variants in CLCN7 cause hypopigmentation and lysosomal storage disease.

Together with its β-subunit OSTM1, ClC-7 performs 2Cl/H exchange across lysosomal membranes. Pathogenic variants in either gene cause lysosome-related pathologies, including osteopetrosis and lysosomal storage. CLCN7 variants can cause recessive or dominant disease.