RNA-Seq for EBJ-ACC affected and control

Experiment ID:ERP009105

Technology:RNA-Seq

Description:In this study, we demonstrate the use of a genome-wide association mapping together with RNA-seq in a reduced number of samples, as an efficient approach to detect the causal mutation for a Mendelian disease. Junctional epidermolysis bullosa is a recessive genodermatosis that manifests with neonatal mechanical fragility of the skin, blistering confined to the lamina lucida of the basement membrane and severe alteration of the hemidesmosomal junctions. In Spanish Churra sheep, junctional epidermolysis bullosa with aplasia cutis congenita (JEB-ACC) has been detected in two commercial flocks. The JEB-ACC locus was mapped to Ovis aries chromosome 11 by GWAS and subsequently fine-mapped to an 868-kb homozygous segment using the identical-by-descent method. The ITGB4, which is located within this region, was identified as the best positional and functional candidate gene. The RNA-seq variant analysis enabled us to discover a 4-bp deletion within exon 33 of the ITGB4 gene (c.4412_4415del). The c.4412_4415del mutation causes a frameshift resulting in a premature stop codon at position 1472 of the integrin ?4 protein. A functional analysis of this deletion revealed decreased levels of mRNA in JEB-ACC skin samples and the absence of integrin ?4 labeling in immunohistochemical assays. Genotyping of c.4412_4415del showed perfect concordance with the recessive mode of the disease phenotype. Selection against this causal mutation will now be used to solve the problem of JEB-ACC in flocks of Churra sheep. Furthermore, the identification of the ITGB4 mutation means that affected sheep can be used as a large mammal animal model for the human form of epidermolysis bullosa with aplasia cutis. Our approach evidences that RNA-seq offers cost-effective alternative to identify variants in the species in which high resolution exome-sequencing is not straightforward.

Source:ERP009105 SRA

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Bulk RNA-Seq processed expression values in Ovis aries

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Library ID Identifier of the RNA-Seq library	Anat. entity ID ID of the anatomical localization of the sample	Anat. entity name Name of the anatomical localization of the sample	Anat. entity author annotation Free text annotation of anatomical localization of the sample as provided by authors	Stage ID ID of the developmental and life stage of the sample	Stage name Name of the developmental and life stage of the sample	Stage author annotation Free text annotation of the developmental and life stage of the sample as provided by authors	Sex Annotation of the sex of the sample	Strain Annotation of the strain of the sample	Time Free text annotation of the time of sampling as provided by authors	Time unit Unit for the time of sampling as provided by authors	Species	Physiological status Physiological status of the organism at time of sampling	Technology	Sequencing platform	Sequenced transcript part Possible values are: full length, all parts of the transcript are sequenced; 3': only the 3' end of the transcript is sequenced; 5': only the 5' end of the transcript is sequenced.	Fragmentation Size of the RNA fragmentation	Run sequencing type Paired-end or single-read run	Total read count Total number of reads for the library.	Mapped read count Number of reads that could be mapped to the transcriptome.	Total UMI count Total number of individual RNA molecules (UMI) for the annotated sample. Only applicable for libraries producing UMIs.	Mapped UMI count Number of UMIs that could be mapped to the transcriptome. Only applicable for libraries producing UMIs.	Distinct rank count When performing a fractional ranking of the genes in the annotated sample, based on their expression level, number of distinct ranks observed, to have a value of the power for distinguishing expression levels. Used as a weight to compute a weighted mean rank accross samples for each gene and compute expression scores in Bgee.	Max rank When performing a fractional ranking of the genes in the annotated sample, based on their expression level, maximum rank attained in the sample. Used to normalize ranks accross samples and compute expression scores in Bgee.	Link to processed expression values See the processed expression value results for this assay
ERX651335	UBERON:0000014	zone of skin	skin samples	UBERON:0000112	sexually immature stage	lamb	NA	Spanish Churra	NA	NA	Ovis aries	NA	Illumina	Illumina HiSeq 2000	FULL_LENGTH	76	paired	34884883	20782877	0	0	19039	21000	Browse results

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