Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptome sequencing of a large human family identifies the impact of rare non-coding variants


ABSTRACT: We have combined high-quality genome sequencing and RNA-sequencing data within a 17-individual, three generation family. Using these data, we have contrasted cis-acting expression, allele-specific expression and splicing quantitative trait loci (collectively termed eQTLs) within the family to eQTLs discovered within a cell-type and ethnicity-matched population sample. We identified that eQTL that exhibit larger effects in the family compared to the population are enriched for rare regulatory and splicing variants and were more likely to influence essential genes. In addition, we identify several large effect-size eQTLs within the family for genes involved in complex disease. Through analysis of eQTLs in a large family we also report the utility of non-coding genome annotation to predicting the effect of rare non-coding variants. We find that a combination of distance to the transcription start site, evolutionary constraint and epigenetic annotation is considerably more informative for predicting the consequence of rare non-coding variants than for common variants. In summary, through transcriptome analyses within a large family we are able to identify the contribution of rare non-coding variants to expression phenotypes and further demonstrate the predictive potential of diverse non-coding genome annotation for interpretation of the impact of rare non-coding variants. RNA-Sequencing of CEPH/UTAH family 1463

ORGANISM(S): Homo sapiens

SUBMITTER: Xin Li 

PROVIDER: E-GEOD-56961 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcriptome sequencing of a large human family identifies the impact of rare noncoding variants.

Li Xin X   Battle Alexis A   Karczewski Konrad J KJ   Karczewski Konrad J KJ   Zappala Zach Z   Knowles David A DA   Smith Kevin S KS   Kukurba Kim R KR   Wu Eric E   Simon Noah N   Montgomery Stephen B SB  

American journal of human genetics 20140901 3


Recent and rapid human population growth has led to an excess of rare genetic variants that are expected to contribute to an individual's genetic burden of disease risk. To date, much of the focus has been on rare protein-coding variants, for which potential impact can be estimated from the genetic code, but determining the impact of rare noncoding variants has been more challenging. To improve our understanding of such variants, we combined high-quality genome sequencing and RNA sequencing data  ...[more]

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