Biology subjects

Rausch, T.

Publications and source records attributed to Rausch, T..

21 records · Page 2Linked to original sources

bioRxiv2019

Distinct and overlapping functions of Miscanthus sinensis MYB transcription factors SCM1 and MYB103 in lignin biosynthesis

Cell wall recalcitrance is a major constraint for the exploitation of lignocellulosic biomass as renewable resource for energy and bio-based products. Transcriptional regulators of the lignin biosynthetic pathway represent promising targets for tailoring lignin content and composition in plant secondary cell walls. A wealth of research in model organisms has revealed that transcriptional regulation of secondary cell wall formation is orchestrated by a hierarchical transcription factor (TF) network with NAC TFs as master regulators and MYB factors in the lower tier regulators. However, knowledge about the transcriptional regulation of lignin biosynthesis in lignocellulosic feedstocks, such as Miscanthus, is limited. Here, we characterized two Miscanthus MYB TFs, MsSCM1 and MsMYB103, and compared their transcriptional impact with that of the master regulator MsSND1. In Miscanthus leaves MsSCM1 and MsMYB103 are expressed at growth stages associated with lignification. Ectopic expression of MsSCM1 and MsMYB103 in tobacco leaves was sufficient to trigger secondary cell wall deposition with distinct sugar and lignin composition. Moreover, RNA-seq analysis revealed that the transcriptional responses to MsSCM1 and MsMYB103 overexpression showed extensive overlap with the response to MsSND1, but were distinct from each other, underscoring the inherent complexity of secondary cell wall formation. Together, MsSCM1 and MsMYB103 represent interesting targets for manipulations of lignin content and composition in Miscanthus towards tailored biomass.

plant biology↗

bioRxiv2017

Germline determinants of the somatic mutation landscape in 2,642 cancer genomes

Cancers develop through somatic mutagenesis, however germline genetic variation can markedly contribute to tumorigenesis via diverse mechanisms. We discovered and phased 88 million germline single nucleotide variants, short insertions/deletions, and large structural variants in whole genomes from 2,642 cancer patients, and employed this genomic resource to study genetic determinants of somatic mutagenesis across 39 cancer types. Our analyses implicate damaging germline variants in a variety of cancer predisposition and DNA damage response genes with specific somatic mutation patterns. Mutations in the MBD4 DNA glycosylase gene showed association with elevated C>T mutagenesis at CpG dinucleotides, a ubiquitous mutational process acting across tissues. Analysis of somatic structural variation exposed complex rearrangement patterns, involving cycles of templated insertions and tandem duplications, in BRCA1-deficient tumours. Genome-wide association analysis implicated common genetic variation at the APOBEC3 gene cluster with reduced basal levels of somatic mutagenesis attributable to APOBEC cytidine deaminases across cancer types. We further inferred over a hundred polymorphic L1/LINE elements with somatic retrotransposition activity in cancer. Our study highlights the major impact of rare and common germline variants on mutational landscapes in cancer.

genomics↗

bioRxiv2017

Multi-platform discovery of haplotype-resolved structural variation in human genomes

The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, and strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three human parent-child trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs ([≥]50 bp) per human genome. We also discover 156 inversions per genome--most of which previously escaped detection. Fifty-eight of the inversions we discovered intersect with the critical regions of recurrent microdeletion and microduplication syndromes. Taken together, our SV callsets represent a sevenfold increase in SV detection compared to most standard high-throughput sequencing studies, including those from the 1000 Genomes Project. The method and the dataset serve as a gold standard for the scientific community and we make specific recommendations for maximizing structural variation sensitivity for future large-scale genome sequencing studies.

genomics↗