Notch2 N-Terminal-Like R

Description

NOTCH2NLR appears to be a nonfunctional pseudogene derived from a partial duplication of the NOTCH2 gene (600275) (Fiddes et al., 2018).

Cloning and Expression

Independently, Fiddes et al. (2018) and Suzuki et al. (2018) identified 4 NOTCH2 paralogs in the human genome resulting from segmental duplications of the ancestral NOTCH2 gene that they called NOTCH2NLA (618023), NOTCH2NLB (618024), NOTCH2NLC (618025), and NOTCH2NLR. NOTCH2NLA, NOTCH2NLB, and NOTCH2NLC encode functional NOTCH2-like proteins. Fiddes et al. (2018) determined that NOTCH2NLR is likely a transcribed pseudogene.

Fiddes et al. (2018) examined human fetal brains and found that the expression pattern of NOTCH2NL genes closely resembled that of NOTCH2, with highest NOTCH2L expression in various radial glia populations, including outer radial glia, as well as astrocytes and microglia.

Using RNA sequencing analysis, Suzuki et al. (2018) found that NOTCH2NLA and NOTCH2NLB were expressed throughout corticogenesis in human fetal cortices, with NOTCH2NLB showing higher expression than NOTCH2NLA. NOTCH2NLC and NOTCH2NLR exhibited low expression throughout corticogenesis. Quantitative RT-PCR followed by direct sequencing confirmed that NOTCH2NLB showed highest expression, followed by NOTCH2NLA, NOTCH2NLC, and NOTCH2NLR. RNA in situ hybridization showed that the NOTCH2NL genes were expressed throughout the ventricular zone in a salt-and-pepper pattern at early stages, whereas NOTCH2 was expressed mostly along the apical part of the ventricular zone. At later stages, NOTCH2 and the NOTCH2NL genes were all expressed in radial glial cells in the outer subventricular zone.

Gene Structure

Independently, Fiddes et al. (2018) and Suzuki et al. (2018) determined that the NOTCH2NL genes, including NOTCH2NLR, contain 5 exons. The first 4 exons of the NOTCH2NL genes correspond to the first 4 exons of the NOTCH2 gene, and exon 5 corresponds to an intronic region of NOTCH2. Fiddes et al. (2018) reported that exon 5 of NOTCH2NLA, NOTCH2NLB, and NOTCH2NLC has a 4-bp deletion compared with the corresponding sequence in NOTCH2, and mutational analysis showed that this 4-bp deletion is essential for NOTCH2NL protein expression. In contrast, NOTCH2NLR lacks the 4-bp deletion and contains many coding variants relative to NOTCH2 and the other NOTCH2NL paralogs, indicating that it is likely a nonfunctional pseudogene.

Mapping

Independently, Fiddes et al. (2018) and Suzuki et al. (2018) mapped the NOTCH2NLR pseudogene to chromosome 1p11.2, near the NOTCH2 gene. They mapped the NOTCH2NLA, NOTCH2NLB, and NOTCH2NLC genes to chromosome 1q21.1.