Neuronal differentiation of human progenitor cells: a window from genetics
Prof. Subrata Sinha,
Ex-Professor and Head,
Department of Biochemistry,
All India Institute of Medical Sciences (AIIMS), New Delhi
Abstract: Dyslexia is a common disability and manifests as reading difficulty. It does not include difficulties
resulting from global deficiencies, either in intelligence or in social opportunity, but is a specific deficit. It could
be predisposed by different genes, and also by gene environment interactions. There may be different
biological components acting in different individuals, giving rise to what are called different ‘endophenotypes’
- a common endpoint on the assessment scale resulting from diverse biological causes. It has with a strong
familial pattern. There is a strong genetic component, to dyslexia. Methods of classical genetics as well as next
generation sequencing have been utilized. There have been a number of candidate 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 lncRNA
that was transcribed in the opposite direction. The same results were also obtained by a bioinformatics related
process, whereby publically available data was analysed 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. Family studies have also enabled us to identify two other pathways which
have evolutionary importance. These could help indicate the cognitive processes that would finally result in
the ability to read, a uniquely human learnt behaviour.