Transcriptome analyses of the human retina identify unprecedented transcript diversity and 3.5 Mb of novel transcribed sequence via significant alternative splicing and novel genes

Farkas, Michael H.; Grant, Gregory R.; White, Joseph A.; Sousa, Maria E; Consugar, Mark; Pierce, Eric A.

doi:10.1186/1471-2164-14-486

Cited by 159 publications

(165 citation statements)

References 87 publications

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“…The trichromatic visual system is one of the dramatic specializations present in the human lineage compared with other mammals. It is not entirely surprising that unique patterns of splicing and/or gene regulation may be related to these specializations (52,53). The model illustrates how incorporation of the e3-encoded sequence within the N-terminal region of CNGA3 may enhance the C-terminal PIP n regulation module by altering intersubunit interactions.…”

Section: Discussionmentioning

confidence: 97%

Alternative Splicing Governs Cone Cyclic Nucleotide-gated (CNG) Channel Sensitivity to Regulation by Phosphoinositides

Dai

Lama-Sherpa

Varnum

2014

Journal of Biological Chemistry

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Background: Variants of photoreceptor CNG channels are produced by alternative splicing of precursor mRNA. Results: Inclusion of an optional exon in human CNGA3 transcripts produces channel isoforms with enhanced sensitivity to phosphoinositides via an allosteric mechanism. Conclusion: Alternative splicing of CNGA3 transcripts controls phosphoinositide regulation of cone CNG channels. Significance: These findings reveal the functional importance of CNGA3 alternative splicing.

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Section: Discussionmentioning

confidence: 97%

Alternative Splicing Governs Cone Cyclic Nucleotide-gated (CNG) Channel Sensitivity to Regulation by Phosphoinositides

Dai

Lama-Sherpa

Varnum

2014

Journal of Biological Chemistry

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“…Examination of human RNA-seq data showed four additional variants occurred in genes with little or no expression in the retina making it unlikely they can cause retinal disease. 19 In addition, we also performed the same exclusions and prioritizations for all 14 compound heterozygous variants and found no promising candidates (Supplementary Table S2).…”

Section: Clinical Diagnosis Revealed a Typical Adult-onset Rp Phenotymentioning

confidence: 99%

A Homozygous Missense Mutation in NEUROD1 Is Associated With Nonsyndromic Autosomal Recessive Retinitis Pigmentosa

Wang¹,

Li²,

Xu³

et al. 2014

Investigative Ophthalmology & Visual Science

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Citation: Wang F, Li H, Xu M, et al. A homozygous missense mutation in NEUROD1 is associated with nonsyndromic autosomal recessive retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2015;56:150-155. DOI: 10.1167/iovs.14-15382 PURPOSE. Mutations in the same gene can lead to different clinical phenotypes. In this study, we aim to identify novel genotype-phenotype correlations and novel disease genes by analyzing an unsolved autosomal recessive retinitis pigmentosa (ARRP) Han Chinese family.METHODS. Whole exome sequencing was performed for one proband from the consanguineous ARRP family. Stringent variants filtering and prioritizations were applied to identify the causative mutation. RESULTS.A homozygous missense variant, c.724G>A; p.V242I, in NEUROD1 was identified as the most likely cause of disease. This allele perfectly segregates in the family and affects an amino acid, which is highly conserved among mammals. A previous study showed that a homozygous null allele in NEUROD1 causes severe syndromic disease with neonatal diabetes, systematic neurological abnormalities, and early-onset retinal dystrophy. Consistent with these results, our patients who are homozygous for a less severe missense allele presented only late-onset retinal degeneration without any syndromic symptoms.CONCLUSIONS. We identified a potential novel genotype-phenotype correlation between NEUROD1 and nonsyndromic ARRP. Our study supports the idea that NEUROD1 is important for maintenance of the retina function and partial loss-of-function mutation in NEUROD1 is likely a rare cause of nonsyndromic ARRP.

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“…We have reported that 100 million reads are necessary to fully cover both the human and mouse neural retina transcriptome (Grant et al 2011;Farkas et al 2012Farkas et al , 2013. Because transcriptome complexity varies between tissues and organisms, it is necessary to independently determine the appropriate depth of coverage for each RNASeq study (Wang et al 2008;Barbosa-Morais et al 2012;Gonzalez-Porta et al 2012).…”

Section: Next Generation Library Preparationmentioning

confidence: 99%

RNA-Seq: Improving Our Understanding of Retinal Biology and Disease

Farkas

Sousa

et al. 2015

Cold Spring Harb Perspect Med

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Transcriptome analyses of the human retina identify unprecedented transcript diversity and 3.5 Mb of novel transcribed sequence via significant alternative splicing and novel genes

Cited by 159 publications

References 87 publications

Alternative Splicing Governs Cone Cyclic Nucleotide-gated (CNG) Channel Sensitivity to Regulation by Phosphoinositides

Alternative Splicing Governs Cone Cyclic Nucleotide-gated (CNG) Channel Sensitivity to Regulation by Phosphoinositides

A Homozygous Missense Mutation in NEUROD1 Is Associated With Nonsyndromic Autosomal Recessive Retinitis Pigmentosa

RNA-Seq: Improving Our Understanding of Retinal Biology and Disease

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