Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor <i>DONSON</i> as the cause of microcephaly-micromelia syndrome.

ABSTRACT: While next-generation sequencing has accelerated the discovery of human disease genes, progress has been largely limited to the "low hanging fruit" of mutations with obvious exonic coding or canonical splice site impact. In contrast, the lack of high-throughput, unbiased approaches for functional assessment of most noncoding variants has bottlenecked gene discovery. We report the integration of transcriptome sequencing (RNA-seq), which surveys all mRNAs to reveal functional impacts of variants at the transcription level, into the gene discovery framework for a unique human disease, microcephaly-micromelia syndrome (MMS). MMS is an autosomal recessive condition described thus far in only a single First Nations population and causes intrauterine growth restriction, severe microcephaly, crani

SUBMITTER: Evrony GD 

PROVIDER: S-EPMC5538549 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature