Identification and characterization of structural and copy number genetic variations in the human X and Y chromosomes and their polygenic effect on neurodegeneration
Faculty: Bratati Kahali (CBR); Chirag Jain (CDS)
The impact of genomic structural and copy-number variations (SV and CNVs) on complex human traits is currently not well-studied, especially so for sex chromosomes and connection to traits manifesting neurodegeneration. These are structural changes in DNA, encompassing inversions, translocations, insertions, deletions, and duplications (multi- copies). These variations account for largest proportion of the nucleotide differences between individuals, and also have substantial functional impact.
This project will comprise, at first, the whole genome sequencing and bioinformatics methods to detect structural and copy number variants at population level. This is a challenging and interesting computational problem given that this kind of data is more valuable in aggregate, that is, joint analysis of all these genomes together increases sample size and statistical power. The computational estimation analysis will be done perusing read-pair, read-depth, and genomeassembly based approaches. The project will later entail determining the statistical genetic associations of structural variants with phenotypes relevant to neurodegeneration, and subsequent polygenic score calculations for these phenotypes. Next, the functional relevance of these findings would be investigated by transcriptome analysis, gene expression studies, phenome wide association studies.
This is a research problem of genetic BIG data and rarely have been carried out before in India at this scale. This will facilitate accurate identification of genetic loci for susceptibilities to complex multifactorial diseases in the Indian population. Therefore, this project will train a student in advanced computational and statistical human genetics.
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