scholarly journals Genetic Interaction between Mfrp and Adipor1 Mutations Affect Retinal Disease Phenotypes

2021 ◽  
Author(s):  
Navdeep Gogna ◽  
Sonia Weatherly ◽  
Fuxin Zhao ◽  
Gayle B Collin ◽  
Jai Pinkney ◽  
...  
Keyword(s):  
Axial Length ◽  
Genetic Interaction ◽  
Retinal Disease ◽  
Gene Interaction ◽  
Photoreceptor Degeneration ◽  
Factorial Anova ◽  
Disease Phenotypes ◽  
Similar Disease ◽  
F2 Generation ◽  
Relationship Of

Adipor1tm1Dgen and Mfrprd6 mutant mice share similar eye disease characteristics. Previously, studies established a functional relationship of ADIPOR1 and MFRP proteins in maintaining retinal lipidome homeostasis and visual function. However, the independent and/or interactive contribution of both the genes to similar disease phenotypes, including fundus spots, decreased axial length and photoreceptor degeneration has yet to be examined. We performed a gene-interaction study where homozygous Adipor1tm1Dgen and Mfrprd6 mice were bred together and the resulting doubly heterozygous F1 offspring were intercrossed to produce 210 F2 progeny. Four-month-old mice from all nine genotypic combinations obtained in the F2 generation were assessed for white spots by fundus photo documentation, for axial length by caliper measurements, and for photoreceptor degeneration by histology. Two-way factorial ANOVA was performed to study individual as well as gene interaction effects on each phenotype. Here, we report the first observation of reduced axial length in Adipor1tmlDgen homozygotes. We show that while Adipor1 and Mfrp interact to affect spotting and degeneration, they act independently to control axial length, highlighting the complex functional association between these two genes. Further examination of the molecular basis of this interaction may help in uncovering mechanisms by which these genes perturb ocular homeostasis.

Power Vector Analysis of Corneal Astigmatism among Chinese over Fifty Years Old: a retrospective cross-sectional study

2020 ◽  
Author(s):  
Yilin Pang ◽  
Xiaoguang Cao ◽  
Xianru Hou ◽  
Li Yuan ◽  
Yongzhen Bao
Keyword(s):  
Axial Length ◽  
Linear Trend ◽  
Linear Regression Analysis ◽  
Corneal Astigmatism ◽  
Vector Analysis ◽  
Cross Sectional ◽  
Age Related ◽  
Relationship Of ◽  
The Relationship ◽  
Cataract Patients

Abstract Background: To investigate the relationship between corneal astigmatism and age, axial length (AL) among Chinese over fifty years old. Methods: This study enrolled 1,082 right eyes of age-related cataract patients over 50 years old in the clinic of Peking University People’s Hospital, Beijing, China. Axial length, magnitude and meridian of anterior corneal astigmatism were measured by IOLMaster. Restricted cubic splines and Spearman rank correlation coefficients were used to investigate the relationship of the magnitude of cornea astigmatism to age and AL. Power vector analysis method and linear regression analysis were used to assess the relationship of the meridian of astigmatism to age and AL. Results: For this study , mean age, AL, and corneal astigmatism value were 72.45 ±9.28 years, 23.90±1.93mm, and 1.12±0.74D, respectively. The magnitude of corneal astigmatism was 0.75D or higher in 63.8% eyes. The magnitude of corneal astigmatism increased with age after 65 years old. This correlation was statistically significant when AL was between 22.00mm and 26.00mm. The vector value in J 0 was inversely correlated with age. The mean vector value change from with-the-rule (WTR) to against-the-rule (ATR) corneal astigmatism was 0.22D/10 years during 50-65 years old and 0.15D/10 years during 65-85 years old, and was 0.22D/10 years in male and 0.12D/10 years in female, respectively. Conclusions: A large proportion of elderly Chinese cataract patients over 50 years old have corneal astigmatism more than 0.75D . There was a non-linear trend from WTR astigmatism towards ATR astigmatism with age, which was more obvious in elder age and in male. When AL is between 22.00mm and 26.00mm, the magnitude of corneal astigmatism increases with age after 65 years old.

Genetic analysis of CAV1 gene in hypertension and metabolic syndrome

2006 ◽  
Vol 95 (04) ◽  
pp. 696-701 ◽  
Author(s):  
Antonio Grilo ◽  
Maria Fernandez ◽  
Manuel Beltrán ◽  
Reposo Ramirez-Lorca ◽  
María González ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Genetic Interaction ◽  
Gene Interaction ◽  
Gene Bank ◽  
Protection Factor ◽  
Hypertensive Patients ◽  
Enos Activity ◽  
Nos3 Gene ◽  
Low Levels ◽  
Trait Locus

SummaryRecently, we reported that the polymorphism 1132T>C (Gene-Bank: AF519768.1) of the NOS3 gene was associated with susceptibility to metabolic syndrome (MS) in hypertensive patients. This suggests that other genes such as CAV1, whose product (CAV1) regulates eNOS activity, could also be related to this phenotype.In this work we investigated the following:i) whether CAV1 is a quantitative trait locus of clustering of atherothrombotic traits associated with MS; ii) whether CVA1 is associated with hypertension or MS in hypertensive patients; and iii) whether genetic interaction between NOS3 and CAV1 is involved in the susceptibility or protection to hypertension associated with MS.To carry out the study, we genotyped 285 randomly selected individuals and 175 hypertensive patients, all of them ≤ 60 years old, with two polymorphisms of the CAV1 gene: the 22285 C>T and the 22375–22375 del AC (GeneBank AF125348), and the 1132T>C polymorphism of the NOS3 gene. To perform sample genotyping, we used pyrosequencing and FRET techniques.The 22285 C-22375–22375 del (Cd) haplotype of CAV1 gene was associated with low levels of blood pressure in the general population. Moreover, it was a genetic protection factor against MS in hypertensive patients. In addition, we found no evidence of gene-gene interaction between NOS3 and CAV1 genes with regard to that phenotype.

scholarly journals Light-Evoked Responses of the Retinal Pigment Epithelium: Changes Accompanying Photoreceptor Loss in the Mouse

2010 ◽  
Vol 104 (1) ◽  
pp. 391-402 ◽  
Author(s):  
Ivy S. Samuels ◽  
Gwen M. Sturgill ◽  
Gregory H. Grossman ◽  
Mary E. Rayborn ◽  
Joe G. Hollyfield ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Structural Changes ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Disease ◽  
Rod Photoreceptor ◽  
Evoked Responses ◽  
Photoreceptor Degeneration ◽  
Rod Photoreceptors ◽  
Slow Piii

Mutations in genes expressed in the retinal pigment epithelium (RPE) underlie a number of human inherited retinal disorders that manifest with photoreceptor degeneration. Because light-evoked responses of the RPE are generated secondary to rod photoreceptor activity, RPE response reductions observed in human patients or animal models may simply reflect decreased photoreceptor input. The purpose of this study was to define how the electrophysiological characteristics of the RPE change when the complement of rod photoreceptors is decreased. To measure RPE function, we used an electroretinogram (dc-ERG)-based technique. We studied a slowly progressive mouse model of photoreceptor degeneration ( Prph Rd2/+), which was crossed onto a Nyxnob background to eliminate the b-wave and most other postreceptoral ERG components. On this background, Prph Rd2/+ mice display characteristic reductions in a-wave amplitude, which parallel those in slow PIII amplitude and the loss of rod photoreceptors. At 2 and 4 mo of age, the amplitude of each dc-ERG component (c-wave, fast oscillation, light peak, and off response) was larger in Prph Rd2/+ mice than predicted by rod photoreceptor activity (RmP3) or anatomical analysis. At 4 mo of age, the RPE in Prph Rd2/+ mice showed several structural abnormalities including vacuoles and swollen, hypertrophic cells. These data demonstrate that insights into RPE function can be gained despite a loss of photoreceptors and structural changes in RPE cells and, moreover, that RPE function can be evaluated in a broader range of mouse models of human retinal disease.

scholarly journals The role of allelic and nonallelic interactions of genes in the mechanism of heterosis

2019 ◽  
Vol 24 ◽  
pp. 177-182
Author(s):  
S. G. Hablak ◽  
Ya. A. Abdullaeva ◽  
L. O. Ryabovol ◽  
Ya. S. Ryabovol
Keyword(s):  
First Generation ◽  
Gene Interaction ◽  
Point Of View ◽  
F1 Hybrids ◽  
Heterosis Effect ◽  
Nonallelic Interactions ◽  
F2 Generation ◽  
Mutant Lines ◽  
Polymeric Interaction

Aim. Studying the heterosis effect from the point of view of allelic and nonallelic gene interaction in F1 hybrids from crossing the arabidopsis ecotypes Col-0 and La-0. Methods. Hybridological method of crossing mutant lines and analysis of the inheritance of the signs of the root system. Results. When plants of different races Col-0 and La-0 cross in the F2 generation, polymeric interaction of genes occurs. In that case splitting in F2 goes in the ratio 15: 1. At the same time, hybrids of the first generation exhibit heterosis, which is manifested in a more powerful development of a rosette of leaves in comparison with the initial forms. Conclusions. The emergence of heterosis in hybrids of the first generation can be explained on the basis of the allelic and nonallelic gene interaction, which creates a favorable combination of genes during hybridization, causing the best manifestation of an economically valuable trait. Keywords: Arabidopsis thaliana (L.) Heynh., heterosis, gene, mutation, race.

scholarly journals The role of the ameiotic1 gene in the initiation of meiosis and in subsequent meiotic events in maize.

Genetics ◽  
1993 ◽  
Vol 135 (4) ◽  
pp. 1151-1166 ◽  
Author(s):  
I Golubovskaya ◽  
Z K Grebennikova ◽  
N A Avalkina ◽  
W F Sheridan
Keyword(s):  
Meiotic Division ◽  
Higher Plants ◽  
Gene Interaction ◽  
Microtubule Organizing Center ◽  
Spindle Fiber ◽  
Chromosome Synapsis ◽  
Organizing Center ◽  
Relationship Of ◽  
The Relationship

Abstract Understanding the initiation of meiosis and the relationship of this event with other key cytogenetic processes are major goals in studying the genetic control of meiosis in higher plants. Our genetic and structural analysis of two mutant alleles of the ameiotic1 gene (am1 and am1-praI) suggest that this locus plays an essential role in the initiation of meiosis in maize. The product of the ameiotic1 gene affects an earlier stage in the meiotic sequence than any other known gene in maize and is important for the irreversible commitment of cells to meiosis and for crucial events marking the passage from premeiotic interphase into prophase I including chromosome synapsis. It appears that the period of ameiotic1 gene function in meiosis at a minimum covers the interval from some point during premeiotic interphase until the early zygotene stage of meiosis. To study the interaction of genes in the progression of meiosis, several double meiotic mutants were constructed. In these double mutants (i) the ameiotic1 mutant allele was brought together with the meiotic mutation (afd1) responsible for the fixation of centromeres in meiosis; and with the mutant alleles of the three meiotic genes that control homologous chromosome segregation (dv1, ms43 and ms28), which impair microtubule organizing center organization, the orientation of the spindle fiber apparatus, and the depolymerization of spindle filaments after the first meiotic division, respectively; (ii) the afd1 mutation was combined with two mutations (dsy1 and as1) affecting homologous pairing; (iii) the ms43 mutation was combined with the as1, the ms28 and the dv1 mutations; and (iv) the ms28 mutation was combined with the dv1 mutation and the ms4 (polymitotic1) mutations. An analysis of gene interaction in the double mutants led us to conclude that the ameiotic1 gene is epistatic over the afd1, the dv1, the ms43 and the ms28 genes but the significance of this relationship requires further analysis. The afd gene appears to function from premeiotic interphase throughout the first meiotic division, but it is likely that its function begins after the start of the ameiotic1 gene expression. The afd1 gene is epistatic over the two synaptic mutations dsy1 and as1 and also over the dv1 mutation. The new ameiotic*-485 and leptotene arrest*-487 mutations isolated from an active Robertson's Mutator stocks take part in the control of the initiation of meiosis.

scholarly journals Contribution of Common Variants in GABRG2, RELN and NRG3 and Interaction Networks to the Risk of Hirschsprung Disease

2016 ◽  
Vol 40 (3-4) ◽  
pp. 509-526 ◽  
Author(s):  
Yang Wang ◽  
Jun Wang ◽  
Ying Zhou ◽  
Zhiyun Wei ◽  
Yongtao Xiao ◽  
...  
Keyword(s):  
Genetic Interaction ◽  
Interaction Analysis ◽  
Hirschsprung Disease ◽  
Gene Interaction ◽  
Han Chinese ◽  
Interaction Networks ◽  
Common Variants ◽  
Chinese Origin ◽  
Ptch1 Gene ◽  
Normal Controls

Background: Hirschsprung disease (HSCR) is a complex and heterogeneous disorder, characterized by a deficit in enteric nervous system. Genome-wide studies implied GABRG2, RELN and NRG3 might be involved in HSCR etiology. Here, we aimed to assess genetic variants in GABRG2, RELN and NRG3 that may confer susceptibility to HSCR and explore genetic interaction networks in HSCR. Methods: Using a strategy that combined case-control study and gene-gene interaction analysis with the MassArray system, we evaluated 24 polymorphisms within GABRG2, RELN and NRG3 in 104 HSCR cases and 151 normal controls of Han Chinese origin. Results: We observed that seven polymorphisms showed statistically significant differences between HSCR subjects and normal controls. For each of the three genes, the haplotypes which combined eight markers were the most significant. Moreover, we recruited SNPsyn, GO enrichment and MDR analyses to interrogate the interactions among GABRG2, RELN, NRG3 and our previous identified PTCH1 gene. Significant interaction networks were found among GABRG2, RELN, and PTCH1. Conclusion: We provide a first indication that common variants of GABRG2, RELN and NRG3 and the GABRG2-RELN-PTCH1 interaction networks might confer altered susceptibility to HSCR in the Han Chinese population, suggesting a potential mechanism underlying HSCR pathogenesis.

scholarly journals Loss of RPGR glutamylation underlies the pathogenic mechanism of retinal dystrophy caused by TTLL5 mutations

2016 ◽  
Vol 113 (21) ◽  
pp. E2925-E2934 ◽  
Author(s):  
Xun Sun ◽  
James H. Park ◽  
Jessica Gumerson ◽  
Zhijian Wu ◽  
Anand Swaroop ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Tandem Repeats ◽  
Mutant Mouse ◽  
Retinal Dystrophy ◽  
Retinal Disease ◽  
Pathogenic Mechanism ◽  
Common Disease ◽  
Photoreceptor Degeneration ◽  
Interaction Domain ◽  
Basic Domain

Mutations in the X-linked retinitis pigmentosa GTPase regulator (RPGR) gene are a major cause of retinitis pigmentosa, a blinding retinal disease resulting from photoreceptor degeneration. A photoreceptor specific ORF15 variant of RPGR (RPGRORF15), carrying multiple Glu-Gly tandem repeats and a C-terminal basic domain of unknown function, localizes to the connecting cilium where it is thought to regulate cargo trafficking. Here we show that tubulin tyrosine ligase like-5 (TTLL5) glutamylates RPGRORF15 in its Glu-Gly–rich repetitive region containing motifs homologous to the α-tubulin C-terminal tail. The RPGRORF15 C-terminal basic domain binds to the noncatalytic cofactor interaction domain unique to TTLL5 among TTLL family glutamylases and targets TTLL5 to glutamylate RPGR. Only TTLL5 and not other TTLL family glutamylases interacts with RPGRORF15 when expressed transiently in cells. Consistent with this, a Ttll5 mutant mouse displays a complete loss of RPGR glutamylation without marked changes in tubulin glutamylation levels. The Ttll5 mutant mouse develops slow photoreceptor degeneration with early mislocalization of cone opsins, features resembling those of Rpgr-null mice. Moreover TTLL5 disease mutants that cause human retinal dystrophy show impaired glutamylation of RPGRORF15. Thus, RPGRORF15 is a novel glutamylation substrate, and this posttranslational modification is critical for its function in photoreceptors. Our study uncovers the pathogenic mechanism whereby absence of RPGRORF15 glutamylation leads to retinal pathology in patients with TTLL5 gene mutations and connects these two genes into a common disease pathway.

scholarly journals Calcineurin B-Like Proteins CBL4 and CBL10 Mediate Two Independent Salt Tolerance Pathways in Arabidopsis

2019 ◽  
Vol 20 (10) ◽  
pp. 2421 ◽  
Author(s):  
Yang Yang ◽  
Chi Zhang ◽  
Ren-Jie Tang ◽  
Hai-Xia Xu ◽  
Wen-Zhi Lan ◽  
...  
Keyword(s):  
Salt Tolerance ◽  
Genetic Interaction ◽  
Critical Role ◽  
Transport Processes ◽  
Interacting Protein ◽  
Sos Pathway ◽  
Calcineurin B ◽  
Whole Plant ◽  
Plant Level ◽  
Relationship Of

In Arabidopsis, the salt overly sensitive (SOS) pathway, consisting of calcineurin B-like protein 4 (CBL4/SOS3), CBL-interacting protein kinase 24 (CIPK24/SOS2) and SOS1, has been well defined as a crucial mechanism to control cellular ion homoeostasis by extruding Na+ to the extracellular space, thus conferring salt tolerance in plants. CBL10 also plays a critical role in salt tolerance possibly by the activation of Na+ compartmentation into the vacuole. However, the functional relationship of the SOS and CBL10-regulated processes remains unclear. Here, we analyzed the genetic interaction between CBL4 and CBL10 and found that the cbl4 cbl10 double mutant was dramatically more sensitive to salt as compared to the cbl4 and cbl10 single mutants, suggesting that CBL4 and CBL10 each directs a different salt-tolerance pathway. Furthermore, the cbl4 cbl10 and cipk24 cbl10 double mutants were more sensitive than the cipk24 single mutant, suggesting that CBL10 directs a process involving CIPK24 and other partners different from the SOS pathway. Although the cbl4 cbl10, cipk24 cbl10, and sos1 cbl10 double mutants showed comparable salt-sensitive phenotype to sos1 at the whole plant level, they all accumulated much lower Na+ as compared to sos1 under high salt conditions, suggesting that CBL10 regulates additional unknown transport processes that play distinct roles from the SOS1 in Na+ homeostasis.

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