The Population Genomics of Human microRNA Gene Copy Number Variation

Date of Award


Degree Type


Degree Name

Master of Science in Biochemistry & Molecular Biology



Chief Instructor

John G. Gibbons

Second Reader

Robert A. Drewell

Third Reader

Justin R. Thackeray


Copy number variation (CNV) is a class of small structural variation defined as loci that vary in their number of copies between individuals due to duplication or deletion. CNV is pervasive in the human genome and can influence phenotype. However, little is known about CNV of genes encoding regulatory microRNAs (miRNAs). We developed a computational method based on variation in read depth to estimate miRNA copy number. This approach was used to quantify the copy number of 1,805 miRNA loci across 161 Yoruban (YRI) and European (CEU) genomes. The vast majority of autosomal miRNA encoding genes were present at a diploid copy number of 2 (1478/1761). However, we identified miRNA loci entirely deleted, and others with average copy number as high as 9. Target gene network-based functional enrichment for the miRNA loci with deleted CNV profiles revealed a variety of significant associations including GTP metabolic processes and protein tetramerization for CEU deleted miRNAs and nervous system development regulation for YRI deleted miRNAs. Additionally, we identified 83 miRNA loci harboring highly differentiated profiles between Yoruban and European populations. Many of these copy number differentiated miRNA genes have been previously associated with cancer susceptibility and progression. Further studies are needed to determine the direct associations between miRNA CNV, miRNA gene expression, target gene expression, and phenotype.

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