scholarly journals Multiple Loss-of-Function Mechanisms Contribute to SCN5A-Related Familial Sick Sinus Syndrome

PLoS ONE ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. e10985 ◽  
Author(s):  
Junhong Gui ◽  
Tao Wang ◽  
Richard P. O. Jones ◽  
Dorothy Trump ◽  
Thomas Zimmer ◽  
...  
Keyword(s):  
Sick Sinus Syndrome ◽  
Loss Of Function ◽  
Multiple Loss

scholarly journals Correction: Multiple Loss-of-Function Mechanisms Contribute to SCN5A-Related Familial Sick Sinus Syndrome

PLoS ONE ◽  
2010 ◽  
Vol 5 (6) ◽  
Author(s):  
Junhong Gui ◽  
Tao Wang ◽  
Richard P. O. Jones ◽  
Dorothy Trump ◽  
Thomas Zimmer ◽  
...  
Keyword(s):  
Sick Sinus Syndrome ◽  
Loss Of Function ◽  
Multiple Loss

scholarly journals Correction: Multiple Loss-of-Function Mechanisms Contribute to SCN5A-Related Familial Sick Sinus Syndrome

PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
Author(s):  
Junhong Gui ◽  
Tao Wang ◽  
Richard P. O. Jones ◽  
Dorothy Trump ◽  
Thomas Zimmer ◽  
...  
Keyword(s):  
Sick Sinus Syndrome ◽  
Loss Of Function ◽  
Multiple Loss

scholarly journals Correction: Multiple Loss-of-Function Mechanisms Contribute to SCN5A-Related Familial Sick Sinus Syndrome

PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
Author(s):  
Junhong Gui ◽  
Tao Wang ◽  
Richard P. O. Jones ◽  
Dorothy Trump ◽  
Thomas Zimmer ◽  
...  
Keyword(s):  
Sick Sinus Syndrome ◽  
Loss Of Function ◽  
Multiple Loss

scholarly journals The NALCN Channel Regulator UNC-80 Functions in a Subset of Interneurons To Regulate Caenorhabditis elegans Reversal Behavior

2019 ◽  
Vol 10 (1) ◽  
pp. 199-210 ◽  
Author(s):  
Chuanman Zhou ◽  
Jintao Luo ◽  
Xiaohui He ◽  
Qian Zhou ◽  
Yunxia He ◽  
...  
Keyword(s):  
Plant Hormone ◽  
Neuronal Excitability ◽  
Resting Membrane Potential ◽  
Loss Of Function ◽  
Wild Type ◽  
C Elegans ◽  
Link Type ◽  
Complex Functions ◽  
And Function ◽  
Multiple Loss

NALCN (Na+leak channel, non-selective) is a conserved, voltage-insensitive cation channel that regulates resting membrane potential and neuronal excitability. UNC79 and UNC80 are key regulators of the channel function. However, the behavioral effects of the channel complex are not entirely clear and the neurons in which the channel functions remain to be identified. In a forward genetic screen for C. elegans mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated multiple loss-of-function mutations in unc-80 and unc-79. C. elegans NALCN mutants exhibited similarly defective MeSa avoidance. Interestingly, NALCN, unc-80 and unc-79 mutants all showed wild type-like responses to other attractive or repelling odorants, suggesting that NALCN does not broadly affect odor detection or related forward and reversal behaviors. To understand in which neurons the channel functions, we determined the identities of a subset of unc-80-expressing neurons. We found that unc-79 and unc-80 are expressed and function in overlapping neurons, which verified previous assumptions. Neuron-specific transgene rescue and knockdown experiments suggest that the command interneurons AVA and AVE and the anterior guidepost neuron AVG can play a sufficient role in mediating unc-80 regulation of the MeSa avoidance. Though primarily based on genetic analyses, our results further imply that MeSa might activate NALCN by direct or indirect actions. Altogether, we provide an initial look into the key neurons in which the NALCN channel complex functions and identify a novel function of the channel in regulating C. elegans reversal behavior through command interneurons.

Multiple loss-of-function putative aminotransferase alleles contribute to low pungency and capsinoid biosynthesis in Capsicum chinense

2015 ◽  
Vol 35 (6) ◽  
Author(s):  
Yoshiyuki Tanaka ◽  
Tomomi Sonoyama ◽  
Yuji Muraga ◽  
Sota Koeda ◽  
Tanjuro Goto ◽  
...  
Keyword(s):  
Capsicum Chinense ◽  
Loss Of Function ◽  
Putative Aminotransferase ◽  
Multiple Loss

Multiple loss-of-function of Arabidopsis gibberellin receptor AtGID1s completely shuts down a gibberellin signal

2007 ◽  
Vol 50 (6) ◽  
pp. 958-966 ◽  
Author(s):  
Satoshi Iuchi ◽  
Hiroyuki Suzuki ◽  
Young-Cheon Kim ◽  
Atsuko Iuchi ◽  
Takashi Kuromori ◽  
...  
Keyword(s):  
Loss Of Function ◽  
Multiple Loss

Multiple loss-of-function 5-O-glucosyltransferase alleles revealed in Vitis vinifera, but not in other Vitis species

2014 ◽  
Vol 127 (11) ◽  
pp. 2433-2451 ◽  
Author(s):  
Yingzhen Yang ◽  
Joanne A. Labate ◽  
Zhenchang Liang ◽  
Peter Cousins ◽  
Bernard Prins ◽  
...  
Keyword(s):  
Vitis Vinifera ◽  
Loss Of Function ◽  
Vitis Species ◽  
Multiple Loss

scholarly journals Multiple loss-of-function variants of taste receptors in modern humans

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Kohei Fujikura
Keyword(s):  
Human Genome ◽  
Mammalian Species ◽  
Taste Receptor ◽  
Population Diversity ◽  
Taste Receptors ◽  
Loss Of Function ◽  
Modern Humans ◽  
Variant Frequency ◽  
Molecular Evolutionary Rates ◽  
Multiple Loss

Abstract Despite recent advances in the knowledge of interindividual taste differences, the underlying genetic backgrounds have remained to be fully elucidated. Much of the taste variation among different mammalian species can be explained by pseudogenization of taste receptors. Here I investigated whether the most recent disruptions of taste receptor genes segregate with their intact forms in modern humans by analyzing 14 ethnically diverse populations. The results revealed an unprecedented prevalence of 25 segregating loss-of-function (LoF) taste receptor variants, identifying one of the most pronounced cases of functional population diversity in the human genome. LoF variant frequency in taste receptors (2.10%) was considerably higher than the overall LoF frequency in human genome (0.16%). In particular, molecular evolutionary rates of candidate sour (14.7%) and bitter (1.8%) receptors were far higher in humans than those of sweet (0.02%), salty (0.05%) and umami (0.17%) receptors compared with other carnivorous mammals, although not all of the taste receptors were identified. Many LoF variants are population-specific, some of which arose even after population differentiation, not before divergence of the modern and archaic human. I conclude that modern humans might have been losing some sour and bitter receptor genes because of high-frequency LoF variants.

scholarly journals Whole-exome sequencing identifies multiple loss-of-function mutations of NF-κB pathway regulators in nasopharyngeal carcinoma

2016 ◽  
Vol 113 (40) ◽  
pp. 11283-11288 ◽  
Author(s):  
Hong Zheng ◽  
Wei Dai ◽  
Arthur Kwok Leung Cheung ◽  
Josephine Mun Yee Ko ◽  
Rebecca Kan ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Somatic Mutations ◽  
Cytidine Deaminase ◽  
Cycle Phase ◽  
Loss Of Function ◽  
Functional Studies ◽  
Whole Exome ◽  
Multiple Loss

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing. An APOBEC cytidine deaminase mutagenesis signature was revealed in the somatic mutations. Noticeably, multiple loss-of-function mutations were identified in several NF-κB signaling negative regulators NFKBIA, CYLD, and TNFAIP3. Functional studies confirmed that inhibition of NFKBIA had a significant impact on NF-κB activity and NPC cell growth. The identified loss-of-function mutations in NFKBIA leading to protein truncation contributed to the altered NF-κB activity, which is critical for NPC tumorigenesis. In addition, somatic mutations were found in several cancer-relevant pathways, including cell cycle-phase transition, cell death, EBV infection, and viral carcinogenesis. These data provide an enhanced road map for understanding the molecular basis underlying NPC.

scholarly journals Mouse models of altered gonadotrophin action: insight into male reproductive disorders

Reproduction ◽  
2014 ◽  
Vol 148 (4) ◽  
pp. R63-R70 ◽  
Author(s):  
Kim C Jonas ◽  
Olayiwola O Oduwole ◽  
Hellevi Peltoketo ◽  
Susana B Rulli ◽  
Ilpo T Huhtaniemi
Keyword(s):  
Mouse Models ◽  
Molecular Mechanisms ◽  
Pituitary Hormones ◽  
Loss Of Function ◽  
Reproductive Disorders ◽  
Human Reproductive ◽  
Multiple Loss ◽  
The Relationship

The advent of technologies to genetically manipulate the mouse genome has revolutionised research approaches, providing a unique platform to study the causality of reproductive disorders in vivo. With the relative ease of generating genetically modified (GM) mouse models, the last two decades have yielded multiple loss-of-function and gain-of-function mutation mouse models to explore the role of gonadotrophins and their receptors in reproductive pathologies. This work has provided key insights into the molecular mechanisms underlying reproductive disorders with altered gonadotrophin action, revealing the fundamental roles of these pituitary hormones and their receptors in the hypothalamic–pituitary–gonadal axis. This review will describe GM mouse models of gonadotrophins and their receptors with enhanced or diminished actions, specifically focusing on the male. We will discuss the mechanistic insights gained from these models into male reproductive disorders, and the relationship and understanding provided into male human reproductive disorders originating from altered gonadotrophin action.

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