Wednesday, November 20, 2019

CCMB Seminar: "Understanding genetics of complex diseases through functional genomics"

4:00 PM

Forum Hall, 4th Floor, Palmer Commons Building

CCMB Seminar Series – sponsored by DCMB
by Dr. Xin He 


GWAS of neuropsychiatric diseases have identified many loci, however, causal variants often remain unknown.  We performed ATAC-seq in human iPSC-derived neurons, and identified thousands of variants affecting chromatin accessibility.  Such variants are highly enriched with risk variants of a range of brain disorders.  We computationally fine-mapped causal variants and experimentally tested their activities using CRISPRi followed by single cell RNA-seq.  Our work provides a framework for prioritizing noncoding disease variants.


The second part of my talk will be focused on genetics of N6-methyladenosine (m6A), a common form of mRNA modification.  m6A plays an important role in regulating various aspects of mRNA metabolism in eukaryotes.  However, little is known about how DNA sequence variations may affect the m6A modification and the role of m6A in common diseases.  We mapped genetic variants associated with m6A levels in 60 Yoruba lymphoblast cell lines.  By leveraging these variants, our analysis provides novel insights of mechanisms regulating m6A installation, and downstream effects of m6A on other molecular traits such as translation rate.  Integrated analysis with GWAS data reveals m6A variation as an important mechanism linking genetic variations to complex diseases.