scholarly journals A Hidden Structural Variation in a Known IRD Gene: A Cautionary Tale of Two New Disease Candidate Genes

2021 ◽  
Author(s):  
Hilary A Scott ◽  
Anna Larson ◽  
Shisong Rong ◽  
Sudeep Mehrotra ◽  
Rossano Butcher ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Vision Loss ◽  
Sequence Data ◽  
Functional Characterization ◽  
Genetic Diagnosis ◽  
Cone Dystrophy ◽  
Potential Candidate ◽  
New Disease ◽  
Functional Assays ◽  
The Impact

Rod cone dystrophy (RCD), also known as retinitis pigmentosa, is an inherited condition leading to vision loss, affecting 1/3500 people. Over 270 genes are known to be implicated in the inherited retinal degenerations (IRDs), yet genetic diagnosis for ~30% IRD of patients remains elusive despite advances in sequencing technologies. The goal of this study was to determine the genetic causality in a family with Rod-cone dystrophy (RCD). Family members were given a full ophthalmic exam at the Retinal Service at MEE and consented to genetic testing. Whole exome sequencing (WES) was performed and variants of interest were Sanger validated. Functional assays were conducted in zebrafish along with splicing assays in relevant cell lines to determine the impact on retinal function. WES identified variants in two potential candidate genes that segregated with disease: GNL3 (G Protein Nucleolar 3) c.1187+3A>C and c.1568-8C>A; and PDE4DIP (Phosphodiester 4D Interacting Protein) c.3868G>A (p.Glu1290Lys) and c.4603G>A (p.Ala1535Thr). Both genes were promising candidates based on their retinal involvement (development and interactions with IRD-associated proteins), however the functional assays did not validate either gene. Subsequent WES reanalysis with an updated bioinformatics pipeline and widened search parameters led to the detection of a 94bp duplication in PRPF31 (pre-mRNA Processing Factor 31) c.73_266dup (p.Asp56GlyfsTer33) as the causal variant. Our study demonstrates the importance of thorough functional characterization of new disease candidate genes, and the value of reanalyzing NGS sequence data, which in our case led to identification of a hidden pathogenic variant in a known IRD gene.

scholarly journals A Hidden Structural Variation in a Known IRD Gene: A Cautionary Tale of Two New Disease Candidate Genes

2021 ◽  
pp. mcs.a006131
Author(s):  
Hilary A Scott ◽  
Anna Larson ◽  
Shi Song Rong ◽  
Sudeep Mehrotra ◽  
Rossano Butcher ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Vision Loss ◽  
Sequence Data ◽  
Functional Characterization ◽  
Genetic Diagnosis ◽  
Cone Dystrophy ◽  
Potential Candidate ◽  
New Disease ◽  
Functional Assays ◽  
The Impact

Rod cone dystrophy (RCD), also known as retinitis pigmentosa, is an inherited condition leading to vision loss, affecting 1/3500 people. Over 270 genes are known to be implicated in the inherited retinal degenerations (IRDs), yet genetic diagnosis for ~30% IRD of patients remains elusive despite advances in sequencing technologies. The goal of this study was to determine the genetic causality in a family with Rod-cone dystrophy (RCD). Family members were given a full ophthalmic exam at the Retinal Service at MEE and consented to genetic testing. Whole exome sequencing (WES) was performed and variants of interest were Sanger validated. Functional assays were conducted in zebrafish along with splicing assays in relevant cell lines to determine the impact on retinal function. WES identified variants in two potential candidate genes that segregated with disease: GNL3 (G Protein Nucleolar 3) c.1187+3A>C and c.1568-8C>A; and PDE4DIP (Phosphodiester 4D Interacting Protein) c.3868G>A (p.Glu1290Lys) and c.4603G>A (p.Ala1535Thr). Both genes were promising candidates based on their retinal involvement (development and interactions with IRD-associated proteins), however the functional assays did not validate either gene. Subsequent WES reanalysis with an updated bioinformatics pipeline and widened search parameters led to the detection of a 94bp duplication in PRPF31 (pre-mRNA Processing Factor 31) c.73_266dup (p.Asp56GlyfsTer33) as the causal variant. Our study demonstrates the importance of thorough functional characterization of new disease candidate genes, and the value of reanalyzing NGS sequence data, which in our case led to identification of a hidden pathogenic variant in a known IRD gene.

scholarly journals Exploring gene networks in two sunflower lines with contrasting leaf senescence phenotype using a system biology approach

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Sebastián Moschen ◽  
Johanna Marino ◽  
Salvador Nicosia ◽  
Janet Higgins ◽  
Saleh Alseekh ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Crop Yield ◽  
Leaf Senescence ◽  
Metabolic Pathways ◽  
Gene Networks ◽  
Expression Profiles ◽  
Functional Characterization ◽  
Inbred Lines ◽  
Strong Impact ◽  
The Impact

Abstract Background Leaf senescence is a complex process, controlled by multiple genetic and environmental variables. In sunflower, leaf senescence is triggered abruptly following anthesis thereby limiting the capacity of plants to keep their green leaf area during grain filling, which subsequently has a strong impact on crop yield. Recently, we performed a selection of contrasting sunflower inbred lines for the progress of leaf senescence through a physiological, cytological and molecular approach. Here we present a large scale transcriptomic analysis using RNA-seq and its integration with metabolic profiles for two contrasting sunflower inbred lines, R453 and B481–6 (early and delayed senescence respectively), with the aim of identifying metabolic pathways associated to leaf senescence. Results Gene expression profiles revealed a higher number of differentially expressed genes, as well as, higher expression levels in R453, providing evidence for early activation of the senescence program in this line. Metabolic pathways associated with sugars and nutrient recycling were differentially regulated between the lines. Additionally, we identified transcription factors acting as hubs in the co-expression networks; some previously reported as senescence-associated genes in model species but many are novel candidate genes. Conclusions Understanding the onset and the progress of the senescence process in crops and the identification of these new candidate genes will likely prove highly useful for different management strategies to mitigate the impact of senescence on crop yield. Functional characterization of candidate genes will help to develop molecular tools for biotechnological applications in breeding crop yield.

scholarly journals PSI-40 Two mitochondrial lineages revealed in North American yak

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 477-477
Author(s):  
Leah K Treffer ◽  
Edward S Rice ◽  
Anna M Fuller ◽  
Samuel Cutler ◽  
Jessica L Petersen
Keyword(s):  
Sequence Data ◽  
Haplotype Network ◽  
Ovis Aries ◽  
Similar Species ◽  
Nucleotide Polymorphisms ◽  
Mt Dna ◽  
Protein Coding ◽  
Sister Clade ◽  
Mtdna Sequence ◽  
The Impact

Abstract Domestic yak (Bos grunniens) are bovids native to the Asian Qinghai-Tibetan Plateau. Studies of Asian yak have revealed that introgression with domestic cattle has contributed to the evolution of the species. When imported to North America (NA), some hybridization with B. taurus did occur. The objective of this study was to use mitochondrial (mt) DNA sequence data to better understand the mtDNA origin of NA yak and their relationship to Asian yak and related species. The complete mtDNA sequence of 14 individuals (12 NA yak, 1 Tibetan yak, 1 Tibetan B. indicus) was generated and compared with sequences of similar species from GeneBank (B. indicus, B. grunniens (Chinese), B. taurus, B. gaurus, B. primigenius, B. frontalis, Bison bison, and Ovis aries). Individuals were aligned to the B. grunniens reference genome (ARS_UNL_BGru_maternal_1.0), which was also included in the analyses. The mtDNA genes were annotated using the ARS-UCD1.2 cattle sequence as a reference. Ten unique NA yak haplotypes were identified, which a haplotype network separated into two clusters. Variation among the NA haplotypes included 93 nonsynonymous single nucleotide polymorphisms. A maximum likelihood tree including all taxa was made using IQtree after the data were partitioned into twenty-two subgroups using PartitionFinder2. Notably, six NA yak haplotypes formed a clade with B. indicus; the other four haplotypes grouped with B. grunniens and fell as a sister clade to bison, gaur and gayal. These data demonstrate two mitochondrial origins of NA yak with genetic variation in protein coding genes. Although these data suggest yak introgression with B. indicus, it appears to date prior to importation into NA. In addition to contributing to our understanding of the species history, these results suggest the two major mtDNA haplotypes in NA yak may functionally differ. Characterization of the impact of these differences on cellular function is currently underway.

scholarly journals Genome-wide association study and gene network analyses reveal potential candidate genes for high night temperature tolerance in rice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raju Bheemanahalli ◽  
Montana Knight ◽  
Cherryl Quinones ◽  
Colleen J. Doherty ◽  
S. V. Krishna Jagadish
Keyword(s):  
Grain Size ◽  
Candidate Genes ◽  
Gene Network ◽  
Genome Wide Association ◽  
Potential Candidate ◽  
Genetic Loci ◽  
Stay Green ◽  
Yield And Quality ◽  
Genome Wide ◽  
Wide Range

AbstractHigh night temperatures (HNT) are shown to significantly reduce rice (Oryza sativa L.) yield and quality. A better understanding of the genetic architecture of HNT tolerance will help rice breeders to develop varieties adapted to future warmer climates. In this study, a diverse indica rice panel displayed a wide range of phenotypic variability in yield and quality traits under control night (24 °C) and higher night (29 °C) temperatures. Genome-wide association analysis revealed 38 genetic loci associated across treatments (18 for control and 20 for HNT). Nineteen loci were detected with the relative changes in the traits between control and HNT. Positive phenotypic correlations and co-located genetic loci with previously cloned grain size genes revealed common genetic regulation between control and HNT, particularly grain size. Network-based predictive models prioritized 20 causal genes at the genetic loci based on known gene/s expression under HNT in rice. Our study provides important insights for future candidate gene validation and molecular marker development to enhance HNT tolerance in rice. Integrated physiological, genomic, and gene network-informed approaches indicate that the candidate genes for stay-green trait may be relevant to minimizing HNT-induced yield and quality losses during grain filling in rice by optimizing source-sink relationships.

Evaluation of Triticum durum–Aegilops tauschii derived primary synthetics as potential sources of heat stress tolerance for wheat improvement

2021 ◽  
Vol 19 (1) ◽  
pp. 74-89
Author(s):  
Amandeep Kaur ◽  
Parveen Chhuneja ◽  
Puja Srivastava ◽  
Kuldeep Singh ◽  
Satinder Kaur
Keyword(s):  
Heat Stress ◽  
Stress Tolerance ◽  
Hexaploid Wheat ◽  
Aegilops Tauschii ◽  
Grain Filling ◽  
World Population ◽  
Potential Candidate ◽  
Terminal Heat Stress ◽  
Heat Stress Tolerance ◽  
The Impact

AbstractAddressing the impact of heat stress during flowering and grain filling is critical to sustaining wheat productivity to meet a steadily increasing demand from a rapidly growing world population. Crop wild progenitor species of wheat possess a wealth of genetic diversity for several biotic and abiotic stresses, and morphological traits and can serve as valuable donors. The transfer of useful variation from the diploid progenitor, Aegilops tauschii, to hexaploid wheat can be done through the generation of synthetic hexaploid wheat (SHW). The present study targeted the identification of potential primary SHWs to introduce new genetic variability for heat stress tolerance. Selected SHWs were screened for different yield-associated traits along with three advanced breeding lines and durum parents as checks for assessing terminal heat stress tolerance under timely and late sown conditions for two consecutive seasons. Heat tolerance index based on the number of productive tillers and thousand grain weight indicated that three synthetics, syn9809 (64.32, 78.80), syn14128 (50.30, 78.28) and syn14135 (58.16, 76.03), were able to endure terminal heat stress better than other SHWs as well as checks. One of these synthetics, syn14128, recorded a minimum reduction in thousand kernel weight (21%), chlorophyll content (2.56%), grain width (1.07%) despite minimum grain-filling duration (36.15 d) and has been selected as a potential candidate for introducing the terminal heat stress tolerance in wheat breeding programmes. Breeding efforts using these candidate donors will help develop lines with a higher potential to express the desired heat stress-tolerant phenotype under field conditions.

scholarly journals The Impact of Vision Loss on Allocentric Spatial Coding

2020 ◽  
Vol 14 ◽  
Author(s):  
Chiara Martolini ◽  
Giulia Cappagli ◽  
Antonella Luparia ◽  
Sabrina Signorini ◽  
Monica Gori
Keyword(s):  
Vision Loss ◽  
Spatial Coding ◽  
The Impact

scholarly journals Getting a grip on the resilience to blur: The impact of simulated vision loss on a visually guided combat sports interaction

2021 ◽  
pp. 101941
Author(s):  
Kai Krabben ◽  
David Mann ◽  
Arnt van Helden ◽  
Youri Kalisvaart ◽  
Daniel Fortin-Guichard ◽  
...  
Keyword(s):  
Vision Loss ◽  
Combat Sports ◽  
Visually Guided ◽  
The Impact

scholarly journals Transcriptome profiling analysis of muscle tissue reveals potential candidate genes affecting water holding capacity in Chinese Simmental beef cattle

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lili Du ◽  
Tianpeng Chang ◽  
Bingxing An ◽  
Mang Liang ◽  
Xinghai Duan ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Candidate Genes ◽  
Molecular Mechanism ◽  
Meat Quality ◽  
Relevant Literature ◽  
Transcriptome Profiling ◽  
Water Holding Capacity ◽  
Potential Candidate ◽  
Protein Protein Interaction ◽  
Water Holding

AbstractWater holding capacity (WHC) is an important sensory attribute that greatly influences meat quality. However, the molecular mechanism that regulates the beef WHC remains to be elucidated. In this study, the longissimus dorsi (LD) muscles of 49 Chinese Simmental beef cattle were measured for meat quality traits and subjected to RNA sequencing. WHC had significant correlation with 35 kg water loss (r = − 0.99, p < 0.01) and IMF content (r = 0.31, p < 0.05), but not with SF (r = − 0.20, p = 0.18) and pH (r = 0.11, p = 0.44). Eight individuals with the highest WHC (H-WHC) and the lowest WHC (L-WHC) were selected for transcriptome analysis. A total of 865 genes were identified as differentially expressed genes (DEGs) between two groups, of which 633 genes were up-regulated and 232 genes were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed that DEGs were significantly enriched in 15 GO terms and 96 pathways. Additionally, based on protein–protein interaction (PPI) network, animal QTL database (QTLdb), and relevant literature, the study not only confirmed seven genes (HSPA12A, HSPA13, PPARγ, MYL2, MYPN, TPI, and ATP2A1) influenced WHC in accordance with previous studies, but also identified ATP2B4, ACTN1, ITGAV, TGFBR1, THBS1, and TEK as the most promising novel candidate genes affecting the WHC. These findings could offer important insight for exploring the molecular mechanism underlying the WHC trait and facilitate the improvement of beef quality.

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