A genomic data viewer for iPad

The Integrative Genomics Viewer (IGV) for iPad, based on the popular IGV application for desktop and laptop computers, supports researchers who wish to take advantage of the mobility of today’s tablet computers to view genomic data and present findings to colleagues

Epidermolysa bullosa in Danish Hereford calves is caused by a deletion in LAMC2 gene

BACKGROUND Heritable forms of epidermolysis bullosa (EB) constitute a heterogeneous group of skin disorders of genetic aetiology that are characterised by skin and mucous membrane blistering and ulceration in response to even minor trauma. Here we report the occurrence of EB in three Danish Hereford cattle from one herd. RESULTS Two of the animals were necropsied and showed oral mucosal blistering, skin ulcerations and partly loss of horn on the claws. Lesions were histologically characterized by subepidermal blisters and ulcers. Analysis of the family tree indicated that inbreeding and the transmission of a single recessive mutation from a common ancestor could be causative. We performed whole genome sequencing of one affected calf and searched all coding DNA variants. Thereby, we detected a homozygous 2.4 kb deletion encompassing the first exon of the LAMC2 gene, encoding for laminin gamma 2 protein. This loss of function mutation completely removes the start codon of this gene and is therefore predicted to be completely disruptive. The deletion co-segregates with the EB phenotype in the family and absent in normal cattle of various breeds. Verifying the homozygous private variants present in candidate genes allowed us to quickly identify the causative mutation and contribute to the final diagnosis of junctional EB in Hereford cattle. CONCLUSIONS Our investigation confirms the known role of laminin gamma 2 in EB aetiology and shows the importance of whole genome sequencing in the analysis of rare diseases in livestock

Integrative Genomics Viewer

Author Manuscript 2012 May 07.To the Editor: Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.National Institute of General Medical Sciences (U.S.) (R01GM074024)National Cancer Institute (U.S.) (R21CA135827)National Human Genome Research Institute (U.S.) (U54HG003067

Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus

Autosomal dominant North Carolina macular dystrophy (NCMD) is believed to represent a failure of macular development. The disorder has been linked to two loci, MCDR1 (chromosome 6q16) and MCDR3 (chromosome 5p15-p13). Recently, non-coding variants upstream of PRDM13 (MCDR1) and a duplication including IRX1 (MCDR3) have been identified. However, the underlying disease-causing mechanism remains uncertain. Through a combination of sequencing studies on eighteen NCMD families, we report two novel overlapping duplications at the MCDR3 locus, in a gene desert downstream of IRX1 and upstream of ADAMTS16. One duplication of 43 kb was identified in nine families (with evidence for a shared ancestral haplotype), and another one of 45 kb was found in a single family. Three families carry the previously reported V2 variant (MCDR1), while five remain unsolved. The MCDR3 locus is thus refined to a shared region of 39 kb that contains DNAse hypersensitive sites active at a restricted time window during retinal development. Publicly available data confirmed expression of IRX1 and ADAMTS16 in human fetal retina, with IRX1 preferentially expressed in fetal macula. These findings represent a major advance in our understanding of the molecular genetics of NCMD and provide insights into the genetic pathways involved in human macular development

The AURORA pilot study for molecular screening of patients with advanced breast cancer–a study of the breast international group

Several studies have demonstrated the feasibility of molecular screening of tumour samples for matching patients with cancer to targeted therapies. However, most of them have been carried out at institutional or national level. Herein, we report on the pilot phase of AURORA (NCT02102165), a European multinational collaborative molecular screening initiative for advanced breast cancer patients. Forty-one patients were prospectively enroled at four participating centres across Europe. Metastatic tumours were biopsied and profiled using an Ion Torrent sequencing platform at a central facility. Sequencing results were obtained for 63% of the patients in real-time with variable turnaround time stemming from delays between patient consent and biopsy. At least one clinically actionable mutation was identified in 73% of patients. We used the Illumina sequencing technology for orthogonal validation and achieved an average of 66% concordance of substitution calls per patient. Additionally, copy number aberrations inferred from the Ion Torrent sequencing were compared to single nucleotide polymorphism arrays and found to be 59% concordant on average. Although this study demonstrates that powerful next generation genomic techniques are logistically ready for international molecular screening programs in routine clinical settings, technical challenges remain to be addressed in order to ensure the accuracy and clinical utility of the genomic data.info:eu-repo/semantics/publishe

Identification of mRNA isoform switching in breast cancer

Abstract Background Alternative splicing provides a major mechanism to generate protein diversity. Increasing evidence suggests a link of dysregulation of splicing associated with cancer. While previous genomic-based studies demonstrated the expression of a handful of tumor-specific isoforms, genome-wide alterations in the balance between isoforms and cancer subtypes is understudied. Result We systematically analyzed the isoform-level expression patterns and isoform switching events of 819 breast tumor and normal samples assayed by mRNA-seq from TCGA project. On average, 2.2 isoforms per gene were detected and 67.5 % of detected genes (i.e. expressed) showed 1–2 isoforms only. While the majority of isoforms for a given gene were positively correlated with each other and the overall gene level, 470 pairs of isoforms displayed an inverse correlation suggesting a switching event. Most of the isoform switching events were associated with molecular subtypes, including a Basal-like-associated switching in CTNND1. 88 genes showed switching independent of subtypes, among which the isoform pattern of PRICKLE1 was associated with a large genomic signature of biological significance. Conclusion Our results reveal that the majority of genes do not undergo complex mRNA splicing within breast cancers, and that there is a general concordance in isoform and gene expression levels in breast tumors. We identified hundreds of isoform switching events across breast tumors, most of which were associated with differences in tumor subtypes. As exemplified by the detailed analysis of CTNND1 and PRICKLE1, these isoform switching events potentially provide new insights into the post-transcriptional regulatory mechanisms of tumor subtypes and cancer biology

A mobile ELF4 delivers circadian temperature information from shoots to roots

Extended Data and Source Data can be found at https://doi.org/10.1038/s41477-020-0634-2Ajuts: the Mas laboratory is funded by the FEDER/Spanish Ministry of Economy and Competitiveness, the Ramon Areces Foundation and the Generalitat de Catalunya (AGAUR). The P.M. laboratory also acknowledges financial support from the CERCA Program, Generalitat de Catalunya and by the Spanish Ministry of Economy and Competitiveness through the Severo Ochoa Program for Centers of Excellence in R&D 2016-2019 (SEV-2015-0533).The circadian clock is synchronized by environmental cues, mostly by light and temperature. Explaining how the plant circadian clock responds to temperature oscillations is crucial to understanding plant responsiveness to the environment. Here, we found a prevalent temperature-dependent function of the Arabidopsis clock component EARLY FLOWERING 4 (ELF4) in the root clock. Although the clocks in roots are able to run in the absence of shoots, micrografting assays and mathematical analyses show that ELF4 moves from shoots to regulate rhythms in roots. ELF4 movement does not convey photoperiodic information, but trafficking is essential for controlling the period of the root clock in a temperature-dependent manner. Low temperatures favour ELF4 mobility, resulting in a slow-paced root clock, whereas high temperatures decrease movement, leading to a faster clock. Hence, the mobile ELF4 delivers temperature information and establishes a shoot-to-root dialogue that sets the pace of the clock in root