Louie Nathaniel Pinpin

Inversion-Mediated Differential Expression of CHRNA7 at Human Chromosome 15q13.3

This abstract was submitted for a poster for the UC Davis Undergraduate Research, Scholarship and Creative Activities Conference in April 2024:

​

Genomic structural variants (SVs, >50 base pairs), comprising deletions, duplications, inversions, and translocations, can contribute to diverse traits and diseases. We hypothesize that inversions, in particular, rearrange the three-dimensional structure and organization of chromatin leading to divergent gene expression in modern humans. Focusing on chromosome 15q13.3 locus implicated in many neurodevelopmental conditions, we identified hundreds of humans carrying a previously-identified 1.7 Mbp inversion. Using existing RNA-seq data from lymphoblastoid cell lines (LCLs) in 731 individuals, we narrowed in on CHRNA7 as exhibiting significantly increased expression due to the inversion. To validate this result, we performed quantitative reverse-transcription polymerase chain reaction (RT-qPCR) of CHRNA7 expression in LCLs and compared results between individuals homozygous for the direct allele and individuals  heterozygous for the inversion allele. We will perform RT-qPCR on additional individuals carrying the chromosome 15q13.3 inversion to show reproducibility of our CHRNA7 gene expression result. As we progress further, we will validate differential expression of additional genes at newly-discovered inversions. Now that high quality human genome assemblies are becoming available, we can now begin to understand how SVs affect gene regulation as well as how they contribute to genetic variation leading to human-specific traits and diseases.​