Page 27 - IBRO_RNA School_Abstract Book

Inherited Dyslexia, neuronal progenitor cells and lncRNA: a

melange of serendipities

Subrata Sinha

Department of Biochemistry, AIIMS,

New Delhi, India

Dyslexia is a specific learning disorder, in which specific difficulties in reading and
writing are manifest without globalized intellectual disability or lack of opportunity
eg. caused by poverty, lack of schooling etc. There is a strong familial association,
pointing out the role of multiple genes and also gene-environment interactions. The
neurodevelopmental origins of most cases of dyslexia are very well established.
Dyslexia affects 5-10% of the population, and could exist by itself or with other
comorbidities, like ADHD. There are a number of genetic studies on dyslexic,
both population, and family-based. Methods of classical genetics as well as next
generation sequencing have been utilized. There have been a number of candi-
date genes demonstrated with varying degrees of replicability. We are studying large
extended multi-generational families from different endogamous groups in order to

understand the genetics biology of dyslexia predisposition. It is expected that the
relative genetic homogeneity within the families would assist in the identification
of susceptible genes. This was done by carefully assessing the family members to
attribute the disability or lack of it, within the family members. Selected members
were assessed by exome sequencing, and the significant results verified in the
entire family. The alteration giving the strongest association was studied. This was
identified to be a 2-nucleotide alteration in the shared stretch of the promoter
of the coding BASP1 gene and its divergent lnc RNA that was transcribed in the
opposite direction. The same results were also obtained by a bioinformatics related

process, whereby publicly available data was analyzed for lncRNAs associated with the
neuronal commitment of progenitors. This coding gene/divergent lncRNA combination
has been studied in human fetus derived neuronal progenitors and has been shown
to code for a novel pathway critical to the neuronal differentiation of progenitor cells.

1. Prajapati B, Fatima M, Fatma M, Maddhesiya P, Arora H, Naskar T, Devasena-
pathy S, Seth P, Sinha S.. Temporal transcriptome analysis of neuronal commitment
reveals the preeminent role of the divergent lncRNA biotype and a critical candidate
gene during differentiation. Cell Death Discov. 2020;6:28. Published 2020 Apr 24.
doi:10.1038/s41420-020-0263-6

2. Identification and epigenetic analysis of divergent long non-coding RNAs in
multilineage differentiation of human Neural Progenitor Cells. Prajapati B, Fatma M,
Maddhesiya P, Sodhi MK, Fatima M, Dargar T, Bhagat R, Seth P, Sinha S. RNA Biol.
2019 Jan;16(1):13-24. doi: 10.1080/15476286.2018.1553482. Epub 2018 Dec 27