Loh Lab

Protein-coding variable number tandem repeat (VNTR) paper published in Science

Ronen Mukamel and Bob Handsaker’s paper on phenotypic effects of protein-coding variable-number-of-tandem repeat (VNTR) polymorphisms (Mukamel*, Handsaker* et al. 2021 Science) is now published — congratulations, Ronen and Bob! This exciting collaboration with Steve McCarroll’s lab found that some of the largest effects of common genetic variants on human phenotypes (including height, biomarkers of health, and hair morphology) arise from coding VNTR polymorphisms that modify size or copy number of protein domains. To enable exploration of the effects of coding VNTR variation in the extensively-phenotyped UK Biobank cohort, we developed new computational strategies for extracting information about VNTR allele lengths from exome-sequencing and SNP-array data sets. The analyses revealed that some of the largest common effects in human genetics have in fact been “hiding in plain sight”: while VNTR polymorphisms were central to human genetics before the advent of high-throughput SNP arrays and DNA sequencing, they became largely invisible to the analytical approaches used in large-scale human genetics studies in the past ~15 years. The strong associations we observed motivate further exploration of the effects of genomic structural variation on human traits. [Science research highlight | Broad news story | The Scientist news story | NIH Research Matters news story ]