Research Projects

Rationale The authors conducted an extensive search on the following databases, a) PUBMED, PUBMED central and other related archives, b) OMIM, c) Biobase-HGMD, and d) Mouse Genome Informatics yet could not comprehensive information upon genetic markers of spina bifida in the Indian population. Considering the neurologic sequel (neurological deficits in lower limbs, neurogenic bladder-bower, hydrocephalus, physical disability), quality of life and the economic burden, it is desirable to predict the possibility of such progeny ahead of conception and take remedial measures in advance. Objectives To identify the genetic determinants of spina bifida and develop a genetic panel to serve as a point-of-care test to predict the risk of spina bifida for Indian population through whole exome sequencing. Hypothesis: Whole exome sequencing enables identification of genetic markers of spina bifida in a dual approach i) Validation of candidate genes identified in animal and human studies in the past ii) Exome-wide unbiased query for likely deleterious variants in potential novel genes Material and Methods Literature Review: List of genes known to be involved in the neurulation pathway or spina bifida will be generated from literature (including animal and human studies). Prospective, multi-centric study with 5-centres across India with a case-parent trios and case-sibling association study design on patients of spina bifida is planned. Unaffected siblings and kids with no spina bifida or other congenital malformations in self or other family members will be incuded as controls. Sample size: 55 cases [15 cases from nodal center & 10 from each collaborating center (n=4)], 110 parents, ~55 siblings and 55 controls: total 275. Observation parameters will include clinical profiling and work-up of participants, pedigree analysis and whole exome sequencing on peripheral blood. List of genes prepared from published will be validated with the results of whole exome sequencing. Exome data analysis, variant identification, variant classification and genotype to phenotype correlation will be performed. Inheritance patterns of identified genetic markers will be studies. Gene pool for spina bifida risk assessment will be developed to serve as a point-of-care test. Translational Value: a) Clinical: Identification of genetic markers of SB and their inheritance pattern b) Prognostic: Development of a genetic panel for predicting the risk of SB c) Research: Identification of the embryological pathways involved in SB d) Artificial Intelligence: Development of a Machine-Learning model to predict the phenotype prenatally based on the Clinical and Genetic data of prospective parents. Deliverables: a) List of genetic markers for spina bifida patients applicable to Indian population b) Inheritance pattern of respective markers c) Gene-pool/ gene-panel to serve as a point of care test for predicting the risk of spina bifida

spina bifida, whole exome sequencing, genetic markers, next-generation sequencing, gene panel, gene pool