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N o v e m b e r 0 5 - 0 6 , 2 0 1 8 | P h i l a d e l p h i a , U S A
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Obesity Summit 2018 & Diabetes Conference 2018 & Laser Photonics Conference 2018 Biomedical Research | ISSN: 0976-1683| Volume 29
3rd INTERNATIONAL OBESITY SUMMIT AND EXPO
&
&
DIABETES, NUTRITION, METABOLISM & MEDICARE
2nd International Conference on
Joint Event on
OF EXCELLENCE
IN INTERNATIONAL
MEETINGS
YEARS
LASER, OPTICS AND PHOTONICS
World Conference on
Khushdeep Bandesh, Biomed Res 2018, Volume 29 | DOI: 10.4066/biomedicalresearch-C7-019
FUNCTIONAL POTENTIAL OF A sub-GWAS
NONCODING VARIANT IN MODULATING THE
TRAIT PHENOTYPE
Decades of rigorous genetic efforts have established type 2 diabetes (T2D)
as apparently an outcome of altered metabolic traits. In this regard, C-pep-
tide, a byproduct of insulin synthesis has been largely neglected. Owing to a
higher plasma half-life (~30mins) than insulin (~4 mins), C-peptide is a precise
measure for insulin secretion and presents independent functional activity.
We performed a two-staged Genome Wide Association Study (GWAS) for plas-
ma C-peptide in Indians (N = 2,706) and identified a novel variant rs4454083
at sub-GWAS significance residing in intron of a GABA receptor-subunit gene
- GABRA6 and simultaneously, in exon of a novel antisense lncRNA, which we
named ARBAG. Expression of GABRA6 triggers fast inhibitory neurotransmis-
sion in human cerebellum and its recruitment to postsynaptic sites is adminis-
tered by C-peptide. Imputation and targeted sequencing of associated region
ensured that rs4454083 is a ‘stand-alone’ SNP. The variant allele (G) which is
a minor allele across all world populations, was seen to be associated with
remarkably higher ARBAG expression in cerebellum. A strong correlation was
detected in expression of GABRA6 and ARBAG in human cerebellar cell-line.
Presence of G allele was observed to stabilize lncRNA transcripts therefore
leading to cellular abundance of ARBAG. Overexpression of ARBAG led to
cleavage of full-length GABRA6 mRNA at/ around the site of complementarity
between both RNAs and ended up in a dissociated GABRA6 protein which is
rendered non-functional owing to separation of its ligand binding domain from
trans-membrane domain. The findings demonstrate role of a sub-GWAS intron-
ic variant in regulating functional mRNA isoforms of associated protein gene.
Biography
Khushdeep Bandesh obtained her PhD early this
year in functional genomics from CSIR-Institute
of Genomics and Integrative Biology, India. She is
currently a post-doctoral fellow at NIDDK. She re-
ceived the ‘Young Scientist Award’ in human genet-
ics for the year 2018 in India. She has worked for
nearly a decade in T2D genetics in diverse human
populations. Her research largely focuses mecha-
nistic understanding of observed genetic associa-
tions on biological grounds.
Khushdeep Bandesh
1National Institute of Diabetes and Digestive
and Kidney Diseases, USA
2CSIR-Institute of Genomics and
Integrative Biology, India