Colby Chiang, Alexandra J Scott, Joe R Davis, Emily K Tsang, Xin Li, Yungil Kim, Tarik Hadzic, Farhan N Damani, Liron Ganel, GTEx Consortium, Stephen B Montgomery, Alexis Battle, Donald F Conrad & Ira M Hall
Nature Genetics volume 49, pages692–699(2017)
https://doi.org/10.1038/ng.3834
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Fine-mapping of causal variants at GWAS loci has proven difficult because the majority (~88%) of causal variants reside in noncoding genomic regions, ...
... as bridges connecting germline genetic variantion to somatic-cell biology.
Loss-of-function variants such as deletions or exon-disrupting MEIs are expected to decrease gene expression, exon duplications should increase gene expression, and neutral markers that tag a nearby causal variant through linkage disequilibrium (LD) should show bidirectional effects.
... because the genotyping error rate for SVs is typically higher than that of other variants, ...
... simulation experiments showed that a 5% increase in SV genotyping error led to a 19.6% decrease in the SV-eQTL mapping rate.
..SVs play an important can disproportionately large role in defining the landscape of genetically regulated gene expression.
Rare variants are difficult to study via traditional eQTL approaches, because any given variant is observed too infrequently within a set of samples to establish a statistically significant relationship with gene expression.
Structural variation is an import source of genetic diversity, but assessing tis functional consequences has beed hindered by technical challenges in detecting and genotyping SVs in large cohorts.
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