Ankyrin Gene Research Articles

Genome-wide identification of Ankyrin (ANK) repeat gene families in three Dendrobium species and the expression of ANK genes in D. officinale under gibberellin and abscisic acid treatments

BackgroundDendrobium Sw. represents one of the most expansive genera within the Orchidaceae family, renowned for its species’ high medicinal and ornamental value. In higher plants, the ankyrin (ANK) repeat protein family is characterized by a unique ANK repeat domain, integral to a plethora of biological functions and biochemical activities. The ANK gene family plays a pivotal role in various plant physiological processes, including stress responses, hormone signaling, and growth. Hence, investigating the ANK gene family and identifying disease-resistance genes in Dendrobium is of paramount importance.ResultsThis research identified 78 ANK genes in Dendrobium officinale Kimura et Migo, 77 in Dendrobium nobile Lindl., and 58 in Dendrobium chrysotoxum Lindl. Subsequently, we conducted comprehensive bioinformatics analyses on these ANK gene families, encompassing gene classification, chromosomal localization, phylogenetic relationships, gene structure and motif characterization, cis-acting regulatory element identification, collinearity assessment, protein-protein interaction network construction, and gene expression profiling. Concurrently, three DoANK genes (DoANK14, DoANK19, and DoANK47) in D. officinale were discerned to indirectly activate the NPR1 transcription factor in the ETI system via SA, thereby modulating the expression of the antibacterial PR gene. Hormonal treatments with GA3 and ABA revealed that 17 and 8 genes were significantly up-regulated, while 4 and 8 genes were significantly down-regulated, respectively. DoANK32 was found to localize to the ArfGAP gene in the endocytosis pathway, impacting vesicle transport and the polar movement of auxin.ConclusionOur findings provide a robust framework for the taxonomic classification, evolutionary analysis, and functional prediction of Dendrobium ANK genes. The three highlighted ANK genes (DoANK14, DoANK19, and DoANK47) from D. officinale may prove valuable in disease resistance and stress response research. DoANK32 is implicated in the morphogenesis and development of D. officinale through its role in vesicular transport and auxin polarity, with subcellular localization studies confirming its presence in the nucleus and cell membrane. ANK genes displaying significant expression changes in response to hormonal treatments could play a crucial role in the hormonal response of D. officinale, potentially inhibiting its growth and development through the modulation of plant hormones such as GA3 and ABA.

An efficient and successful outcome after haematopoietic stem cell transplantation in a patient with an LPS-responsive beige-like anchor gene mutation.

Lipopolysaccharide (LPS)-responsive beige ankyrin (LRBA) gene mutations were first reported as the cause of immunodeficiency syndromes and autoimmunity in 2012. The majority of LRBA patients have multiple organ system involvement and a complex clinical phenotype. Herein we present a comprehensive account on the disease progression and transplantation procedure in a patient with LRBA deficiency who exhibited progressive autoimmune disease symptoms along with recurrent pulmonary infections since the age of 6 years old. Despite receiving abatacept therapy and immunoglobulin replacement treatments to manage the symptoms, but the symptoms still progressed. Therefore, nine years after disease onset, patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT). The patient experienced acute and chronic graft-versus-host disease (GVHD) and recurrent infections after transplantation. During one and a half years of follow-up, we found that allogeneic haematopoietic stem cell transplantation can relieve the symptoms of autoimmune disease in patients with LRBA deficiency, and marked clinical improvement and recovery of immune function were observed following stem cell transplantation.

Comparative Transcriptome Analysis Reveals the Genes and Pathways Related to Wheat Root Hair Length.

Tube-like outgrowths from root epidermal cells, known as root hairs, enhance water and nutrient absorption, facilitate microbial interactions, and contribute to plant anchorage by expanding the root surface area. Genetically regulated and strongly influenced by environmental conditions, longer root hairs generally enhance water and nutrient absorption, correlating with increased stress resistance. Wheat, a globally predominant crop pivotal for human nutrition, necessitates the identification of long root hair genotypes and their regulatory genes to enhance nutrient capture and yield potential. This study focused on 261 wheat samples of diverse genotypes during germination, revealing noticeable disparities in the length of the root hair among the genotypes. Notably, two long root hair genotypes (W106 and W136) and two short root hair genotypes (W90 and W100) were identified. Transcriptome sequencing resulted in the development of 12 root cDNA libraries, unveiling 1180 shared differentially expressed genes (DEGs). Further analyses, including GO function annotation, KEGG enrichment, MapMan metabolic pathway analysis, and protein-protein interaction (PPI) network prediction, underscored the upregulation of root hair length regulatory genes in the long root hair genotypes. These included genes are associated with GA and BA hormone signaling pathways, FRS/FRF and bHLH transcription factors, phenylpropanoid, lignin, lignan secondary metabolic pathways, the peroxidase gene for maintaining ROS steady state, and the ankyrin gene with diverse biological functions. This study contributes valuable insights into modulating the length of wheat root hair and identifies candidate genes for the genetic improvement of wheat root traits.

Novel mutation in alpha-spectrin gene in Saudi patients with hereditary spherocytosis

Hereditary spherocytosis (HS) is the most common hereditary hemolytic disorder induced by red blood cell (RBC) membrane defect. This study was undertaken to determine mutations in genes associated with RBC membrane defect in patients with HS such as α-spectrin gene (SPTA1), β-spectrin gene (SPTB), ankyrin gene (ANK1), band 3 anion transport gene (SLC4A1) and erythrocyte membrane protein band 4.1 gene (EPB41). Blood samples were collected from 23 unrelated patients with HS. Patients were diagnosed according to the guidelines from the British Society for Hematology. All hematological examinations for the determination of RBC abnormalities and osmotic fragility tests were conducted. Genomic DNA were extracted from peripheral blood cells and coding exons of known genes for hereditary spherocytosis were enriched using Roche/KAPA sequence capture technology and sequenced on an Illumina system via next-generation sequencing (NGS). The data showed that most of the HS patients confirmed splenomegaly and showed elevated reticulocytes and abnormal bilirubin values. NGS analysis identified the heterozygous variant c.5501G > A in the exon 39 of SPTA1 gene, resulted in a Trp1834*, which leads to a premature stop codon and subsequent mRNA degradation (nonsense- mediated decay) or truncation in α spectrin. Moreover, our data also revealed conventional mutations in genes SPTB, ANK, SLC4A1 and EBP41 in severe patients of HS. In short, this is the first report that determined a novel mutation c.5501G > A in SPTA1 gene in the Saudi population. To the best of our knowledge, this variant c.5501G > A has not been described in global literature so far. This novel mutation in SPTA1 gene is unique in the Saudi population.

Splenectomy improves erythrocyte functionality in spherocytosis based on septin abundance, but not maturation defects.

Splenectomy improves the clinical parameters of patients with hereditary spherocytosis, but its potential benefit to red blood cell (RBC) functionality and the mechanism behind this benefit remain largely overlooked. Here, we compared 7 nonsplenectomized and 13 splenectomized patients with mutations in the β-spectrin or the ankyrin gene. We showed that hematological parameters, spherocyte abundance, osmotic fragility, intracellular calcium, and extracellular vesicle release were largely but not completely restored by splenectomy, whereas cryohemolysis was not. Affected RBCs exhibited decreases in β-spectrin and/or ankyrin contents and slight alterations in spectrin membrane distribution, depending on the mutation. These modifications were found in both splenectomized and nonsplenectomized patients and poorly correlated with RBC functionality alteration, suggesting additional impairments. Accordingly, we found an increased abundance of septins, small guanosine triphosphate-binding cytoskeletal proteins. Septins-2, -7, and -8 but not -11 were less abundant upon splenectomy and correlated with the disease severity. Septin-2 membrane association was confirmed by immunolabeling. Except for cryohemolysis, all parameters of RBC morphology and functionality correlated with septin abundance. The increased septin content might result from RBC maturation defects, as evidenced by (1) the decreased protein 4.2 and Rh-associated glycoprotein content in all patient RBCs, (2) increased endoplasmic reticulum remnants and endocytosis proteins in nonsplenectomized patients, and (3) increased lysosomal and mitochondrial remnants in splenectomized patients. Our study paves the way for a better understanding of the involvement of septins in RBC membrane biophysical properties. In addition, the lack of restoration of septin-independent cryohemolysis by splenectomy may call into question its recommendation in specific cases.

Male-killing mechanisms vary between Spiroplasma species.

Male-killing, a male-specific death of arthropod hosts during development, is induced by Spiroplasma (Mollicutes) endosymbionts of the Citri-Poulsonii and the Ixodetis groups, which are phylogenetically distant groups. Spiroplasma poulsonii induces male-killing in Drosophila melanogaster (Diptera) using the Spaid toxin that harbors ankyrin repeats, whereas little is known about the origin and mechanisms of male-killing induced by Spiroplasma ixodetis. Here, we analyzed the genome and the biological characteristics of a male-killing S. ixodetis strain sHm in the moth Homona magnanima (Tortricidae, Lepidoptera). Strain sHm harbored a 2.1 Mb chromosome and two potential plasmids encoding Type IV effectors, putatively involved in virulence and host-symbiont interactions. Moreover, sHm did not harbor the spaid gene but harbored 10 ankyrin genes that were homologous to those in other S. ixodetis strains. In contrast to the predominant existence of S. poulsonii in hemolymph, our quantitative PCR assays revealed a systemic distribution of strain sHm in H. magnanima, with particularly high titers in Malpighian tubules but low titers in hemolymph. Furthermore, transinfection assays confirmed that strain sHm can infect cultured cells derived from distantly related insects, namely Aedes albopictus (Diptera) and Bombyx mori (Lepidoptera). These results suggest different origins and characteristics of S. ixodetis- and S. poulsonii-induced male-killing.

Red-light radiation: does it enhance memory by increasing hippocampal LRP-1 and TRPA-1 genes expression?

Purpose Despite the extensive efforts to treat the leading cause of neurodegenerative diseases (ND), a little progress has been reported. Red light might affect ND through many specific mechanisms. The purpose of this investigation is to explore the effect of red light on the expression of low-density lipoprotein receptor-1 (LRP-1) and transient receptor potential ankyrin-1 (TRPA-1) gene in the hippocampus, and the serum melatonin level (SML) of the lipopolysaccharide (LPS)-induced neuro-inflammated rats. Materials and methods Red-light therapy was implemented using a wavelength 630 nm under different light conditions and the passive avoidance (PA) and Y-Maze tests were employed to assess memory performance. To evaluate the LRP-1 and TRPA-1 genes expression, quantitive real-time polymerase chain reaction was performed. To measure the SML, ELISA was performed before and after the red-light radiation. Results LPS caused memory impairment in both behavioral tests. Red-light therapy improved PA memory in all light conditions (p < .001). However, in Y-maze, only the red-light radiation during light and dark cycles, improved memory (p < .01 and p < .001, respectively). In addition, red-light radiation caused significant increase in SML (p < .05). The LRP-1 and TRPA-1 genes expression increased significantly during the dark phase in the red light radiated group compared to non-radiated group (p < .001). Conclusions Taken together, the results suggest that red-light therapy can reduce the complications of memory impairment in rats. This study has found that red-light therapy demonstrates higher effect during the period of dark phase compared to light phase. No doubt, further experimental studies would help us to establish a greater degree of accuracy on this matter.

Alhudaj: CpG islands Detection Tool in Mammalian Genome Using C++

One of the unique combinations in the mammalian genome, that revolutionized concepts in the fields of genetics and molecular pathology is what is termed the CpG islands. However, the accurate and rapid determination of CpG islands for DNA sequences remains experimentally and computationally challenging. The main goal for this project to design an offline, cross-platform CpG islands detection tool. The Algorithm implemented for this study was the traditional sliding window algorithm by using the C++ programming language. Three datasets were used for evaluating the performance of the application. The ANK1 gene, SPTB gene, and RET gene sequence files were obtained from NCBI. In this study, the highest CGIs were reported in ANK1 (ankyrin 1) Gene which scored 13 successive islands whereas the lowest score was reported in RET (ret proto-oncogene) Gene which shows only 6 islands. Generally, the program fulfills the boundaries limits as expected. We strongly recommend for further work, the implementation of other algorithms in addition to the sliding window algorithm such as Hidden Markov Model (HMM).

A cluster of Ankyrin and Ankyrin-TPR repeat genes is associated with panicle branching diversity in rice.

The number of grains per panicle is an important yield-related trait in cereals which depends in part on panicle branching complexity. One component of this complexity is the number of secondary branches per panicle. Previously, a GWAS site associated with secondary branch and spikelet numbers per panicle in rice was identified. Here we combined gene capture, bi-parental genetic population analysis, expression profiling and transgenic approaches in order to investigate the functional significance of a cluster of 6 ANK and ANK-TPR genes within the QTL. Four of the ANK and ANK-TPR genes present a differential expression associated with panicle secondary branch number in contrasted accessions. These differential expression patterns correlate in the different alleles of these genes with specific deletions of potential cis-regulatory sequences in their promoters. Two of these genes were confirmed through functional analysis as playing a role in the control of panicle architecture. Our findings indicate that secondary branching diversity in the rice panicle is governed in part by differentially expressed genes within this cluster encoding ANK and ANK-TPR domain proteins that may act as positive or negative regulators of panicle meristem's identity transition from indeterminate to determinate state.

Sequence and haplotypes of ankyrin 1 gene (ANK1) and their association with carcass and meat quality traits in yak.

Ankyrin 1 (ANK1) gene has been demonstrated to be a functional candidate gene for meat quality that helps to constitute and maintain the structure of the cell skeleton. In this study, three contiguous ANK1 regions from yak were analyzed using polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP). As a result, nine single-nucleotide polymorphisms (SNPs) were identified, four of them in the coding region and three (c.179 C/A, c.250 G/C, and c.313 C/T) putatively resulting in amino acid changes (p. Ala 60 Glu, p. Asp 84 His, and p. Pro 105 Ser). Some SNPs in promoter region were located within or nearby the putative transcription factor binding sites, such as Sp1 and GATA, which might have an impact on the expression of the yak ANK1 gene. The presence of C1-D3 and C1-A3 were associated with an increased hot carcass weight (p = 0.0045) and a decreased drip loss rate (p = 0.0046). The presence of B1-B3, C1-A3 and C1-D3 had decreased Warner-Bratzler shear force (p = 0.0066, p = 0.0343 and p = 0.0004). The presence of one and two copies of B1-B3 and C1-A3 had decreased Warner-Bratzler shear force (p = 0.0005 and p = 0.0443), and C1-A3 had also decreased drip loss rate (p = 0.0164). These findings indicated that genetic variations of the ANK1 gene would be a preferable biomarker for the improvement of yak meat quality.

Ankyrins and neurological disease.

Ankyrins are scaffolding proteins widely expressed throughout the nervous system. Ankyrins recruit diverse membrane proteins, including ion channels and cell adhesion molecules, into specialized subcellular membrane domains. These domains are stabilized by ankyrins interacting with the spectrin cytoskeleton. Ankyrin genes are highly associated with a number of neurological disorders, including Alzheimer's disease, schizophrenia, autism spectrum disorders, and bipolar disorder. Here, we discuss ankyrin function and their role in neurological disease. We propose mutations in ankyrins contribute to disease through two primary mechanisms: 1) altered neuronal excitability by disrupting ion channel clustering at key excitable domains, and 2) altered neuronal connectivity via impaired stabilization of membrane proteins.

Efficacy of cytochemical tests in gene analysis of hereditary spherocytosis: a case study of six patients with different disease subtypes

ABSTRACT Objectives In this study, clinical and biochemical methods were utilized to predict the final diagnosis of hereditary spherocytosis (HS), correlate the diagnosis with splenectomy, and examine the usefulness of this approach. Methods We biochemically and cytochemically analysed erythrocyte membrane proteins before making a final HS diagnosis based on gene analysis to compare diagnostic approaches. The clinical features of six patients with various subtypes of HS and symptoms were observed by blood analysis using eosin-5′-maleimide staining, biochemical analysis using sodium dodecyl sulphate – polyacrylamide gel electrophoresis with western blotting, and mass spectrometry. Finally, diagnostic membrane gene analysis was performed. Results Five of the six patients showed mild to moderate or severe anaemia, and the other patient was non-anaemic; all six patients showed faint eosin-5′-maleimide staining. In western blotting of erythrocyte membrane proteins, all six patients (three with β-spectrin, two with ankyrin, and one with SLC4A1 anomalies) showed low-molecular-weight peptide fragments, which were confirmed by mass spectrometry in the region corresponding to the band 3 protein. The two patients with an ankyrin gene anomaly exhibited severe anaemia, and two patients with simultaneous SLC4A1, SPTB, and UGT1A1 anomalies exhibited mild anaemia and hyperbilirubinemia. Discussion We determined the relationship among clinical features, cytochemical parameters, and gene anomalies in six patients with newly diagnosed HS while referring to previously published cases. Conclusion These findings reveal a close relationship between clinical features and membrane characteristics in HS, which can facilitate diagnosis and inform treatment.

Human ankyrins and their contribution to disease biology: An update

Ankyrins (Ank)are ubiquitously expressed proteins that play a critical role in the integrity of cytoskeleton and cellular signalling. Their presence in metazoans and evolutionary conserved protein primary sequence indicates their functional significance. Tissue-specific isoforms and an array of transcript variants make this protein one of the indispensable cellular components. Membrane-binding domains consist of ankyrin repeats that bind with several functional membrane proteins that enable maintaining cellular integrity. Cytosolic ankyrins help in cellular signal transduction. Linkage studies and recent genome-wide association studies uncovered the pathogenic roles of ankyrins (ankyrin-R, ankyrin-B and ankyrin-G) in several diseases, such as hereditary spherocytosis, long QT syndrome, intellectual disability, and CRASH syndrome, among several others. Identification of Ank3 in celiac disease may potentially explain the link between neuronal health and immunity. It is thus warranted to investigate the role of neuronal factors in immune diseases and vice versa. In this review, we briefly discussed the contribution of ankyrin genes to human diseases.

Comparative analysis of ankyrin (ANK) genes of five capripoxviruses isolate strains from Xinjiang province in China

BackgroundSheeppox and goatpox are both economically important animal diseases in which pathogens are goatpox virus (GTPV) and sheeppox virus (SPPV). They can’t cause cross-species infection between sheep and goats in general. But in recent decades, the infection of sheep by goatpox or goats by sheeppox has been reported. The literature has indicated that the occurrence of these cases has a significant and direct relationship with mutations of ankyrin genes families (ANK genes 010,138,140,141.2,145) located in two-terminal regions of capripoxvirus genomes. So it is very important to decipher these nucleotides and their coding amino acid sequences of the five genes regarded as host range and virulence factors for effective prevention and control of capripoxvirus diseases.MethodsIn this study, all the ankyrin genes of three goatpox virus, two sheeppox virus, and one GTPV vaccine strains from Nanjiang areas of Xinjiang province of China during 2010–2011 were collected, amplified, cloned and sequenced. The sequence of every ankyrin genes has been compared with not only sequences from six viruses but also all sequences from three species of capripoxvirus genus from Gene bank, and every ANK gene’s mutated nucleotides and amino acids have been screened, and the relationship of genetic evolution among different virus strains has been analyzed, as well as the domain architecture of these genes was forecasted and analyzed.ResultsThe six capripoxvirus strains can be well-distinguished GTPV and SPPV based on five ANK genes’ sequence identicalness except for GTPV-SS strain, which showed higher identicalness with SPPV. The ANK gene sequence of the GTPV-SS strain was 100% identical with SPPV-M1 (ANK138,140,145) and SPPV-M2 (ANK138,145), respectively. Phylogenetically, these six capripoxvirus strains were also grouped into the same cluster of India reference strains in lineages and showed extreme identical conservative or variable regions with India capripoxvirus isolates by sequence alignment. Moreover, for the functional domains, these ANK genes of capripoxvirus except for ANK gene 145, are identical in size, and ANK genes 145 of SPPV are usually 100 bp (approximately 30 aa) longer than those of GTPV and eventually form a PRANC domain at C-terminus.ConclusionsThe isolated strain of GTPV-SS may be a cross-species infection or the collected material was contaminated, and the inferred Capripox outbreak in Xinjiang in 2010 can be introduced from India. ANK genes 138,140,141.2 and 145 of capripoxvirus can be used as the target genes to identify GTPV and SPPV. Moreover, the four ANK genes determining the host range are more significant than the ANK gene 010. These ANK genes play combining roles for their function.

Construction and purification of ANK gene deleted recombinant goatpox virus.

Sheeppox virus (SPPV) and goatpox virus (GTPV) are two pathogens of host specificity. Previous studies have hypothesized that ankyrin (ANK) family may play an important role in determining host range of SPPV and GTPV. In order to verify the function of ANK proteins, it is critical to generate and purify the ANK gene deleted GTPV. In this study, the GFP gene as a reporter gene was connected with two homologous arms of ANK gene by fusion PCR. The ANK gene deleted transfer vectors were generated by inserting the PCR products into PET42b, and were transfected into testicular primary cells which were infected by GTPV. The rGTPV were identified as green fluorescence positive and properly purified. The results showed that GFP gene and two homologous arms of ANK gene were connected. The sequence was inserted in PET42b to form ANK deleted transfer vector. ANK deleted rGTPV was generated successfully by transferring vector and GTPV in cells. The ANK deleted rGTPV was purified and identified in this study. The study successfully generated the ANK deleted rGTPV. It overcomes the technical barrier for future studies about the function of ANK genes.

The ankyrin repeat gene family in Capsicum spp: Genome-wide survey, characterization and gene expression profile

The ankyrin (ANK) repeat protein family is largely distributed across plants and has been found to participate in multiple processes such as plant growth and development, hormone response, response to biotic and abiotic stresses. It is considered as one of the major markers of capsaicin content in pepper fruits. In this study, we performed a genome-wide identification and expression analysis of genes encoding ANK proteins in three Capsicum species: Capsicum baccatum, Capsicum annuum and Capsicum chinense. We identified a total of 87, 85 and 96 ANK genes in C. baccatum, C. annuum and C. chinense genomes, respectively. Next, we performed a comprehensive bioinformatics analysis of the Capsicum ANK gene family including gene chromosomal localization, Cis-elements, conserved motif identification, intron/exon structural patterns and gene ontology classification as well as profile expression. Phylogenetic and domain organization analysis grouped the Capsicum ANK gene family into ten subfamilies distributed across all 12 pepper chromosomes at different densities. Analysis of the expression of ANK genes in leaf and pepper fruits suggested that the ANKs have specific expression patterns at various developmental stages in placenta tissue. Our results provide valuable information for further studies of the evolution, classification and putative functions of ANK genes in pepper.

Casein Kinase 1δ Stabilizes Mature Axons by Inhibiting Transcription Termination of Ankyrin.

After axon outgrowth and synapse formation, the nervous system transitions to a stable architecture. In C.elegans, this transition is marked by the appearance of casein kinase 1δ (CK1δ) in the nucleus. In CK1δ mutants, neurons continue to sprout growth cones into adulthood, leading to a highly ramified nervous system. Nervous system architecture in these mutants is completely restored by suppressor mutations in ten genes involved in transcription termination. CK1δ prevents termination by phosphorylating and inhibiting SSUP-72. SSUP-72 would normally remodel the C-terminal domain of RNA polymerase in anticipation of termination. The antitermination activity of CK1δ establishes the mature state of a neuron by promoting the expression of the long isoform of a single gene, the cytoskeleton protein Ankyrin.

PS1200 IDENTIFICATION OF MUTATIONS IN RED CELL MEMBRANOPATHIES USING NGS‐TARGETED SEQUENCING PANEL

Background:Red cell membranopathies refers to genetically and phenotypically heterogenous disorders due to defects in red cell membrane and skeletal proteins. Phenotypes vary from severe transfusion‐dependent hemolytic anemia to fully compensated hemolysis. Causative genes implicated in RBC membranopathies are numerous, making a gene‐by‐gene approach time consuming, expensive and labor intensive. Use of Next Generation Sequencing (NGS) targeted sequencing panel can expedite the molecular diagnosis after routine laboratory tests.Aims:This study aimed at defining a strategy for effective diagnosis of RBC membrane defects and identification of pathogenic mutations associated with the disease.Methods:Patients with clinical symptoms of hemolytic anemia, jaundice, hepatosplenomegaly and some requiring frequent blood transfusions were recruited in this study. Blood was collected from the patients after informed consent. Peripheral blood smear examination and flow cytometric based EMA binding test were performed and identification of mutations in red cell membrane proteins was done using NGS‐targeted sequencing panel. The relationship between gene mutations and clinical phenotypes was analyzed by In silico prediction tools such as SIFT, Polyphen2.Results:We identified mutations in 21 cases of Hemolytic Anemia (HA) in membrane protein‐coding genes using NGS‐targeted sequencing panel. Five Hereditary Spherocytosis (HS) patients were diagnosed with mutations in ankyrin (ANK1) gene, 3 patients with alpha spectrin (SPTA1) gene and 4 patients with beta spectrin (SPTB) gene. Band 3 (SLC4A1) gene mutations was identified in two HS cases and in 2 with dRTA cases. Five patients showed mutation in PIEZO1 gene causing Hereditary xerocytosis (HX). Twelve novel mutations were found as shown in Table 1.Summary/Conclusion:RBC membranopathies showed highly varied etiology. Our experience demonstrates the high diagnostic yield of NGS for molecular diagnosis of RBC membrane disorders associated with defects in large genes. Timely detection of the disorder not only offers therapeutic benefits for our patients but is likely to help in genetic counseling and future antenatal diagnosis, if required.image

A cross-brain regions study of ANK1 DNA methylation in different neurodegenerative diseases.

Recent epigenome-wide association studies in Alzheimer's disease have highlighted consistent robust neuropathology-associated DNA hypermethylation of the ankyrin 1 (ANK1) gene in the cortex. The extent to which altered ANK1 DNA methylation is also associated with other neurodegenerative diseases is not currently known. In the present study, we used bisulfite pyrosequencing to quantify DNA methylation across 8 CpG sites within a 118bp region of the ANK1 gene across multiple brain regions in Alzheimer's disease, Vascular dementia, Dementia with Lewy bodies, Huntington's disease, and Parkinson's disease. We demonstrate disease-associated ANK1 hypermethylation in the entorhinal cortex in Alzheimer's disease, Huntington's disease, and Parkinson's disease, whereas in donors with Vascular dementia and Dementia with Lewy bodies, we observed elevated ANK1 DNA methylation only in individuals with coexisting Alzheimer's disease pathology. We did not observe any disease-associated differential ANK1 DNA methylation in the striatum in Huntington's disease or the substantia nigra in Parkinson's disease. Our data suggest that ANK1 is characterized by region and disease-specific differential DNA methylation in multiple neurodegenerative diseases.

Ankyrin domain encoding genes from an ancient horizontal transfer are functionally integrated into Nasonia developmental gene regulatory networks

BackgroundHow regulatory networks incorporate additional components and how novel genes are functionally integrated into well-established developmental processes are two important and intertwined questions whose answers have major implications for understanding the evolution of development. We recently discovered a set of lineage-restricted genes with strong and specific expression patterns along the dorsal-ventral (DV) axis of the embryo of the wasp Nasonia that may serve as a powerful system for addressing these questions. We sought to both understand the evolutionary history of these genes and to determine their functions in the Nasonia DV patterning system.ResultsWe have found that the novel DV genes are part of a large family of rapidly duplicating and diverging ankyrin domain-encoding genes that originated most likely by horizontal transfer from a prokaryote in a common ancestor of the wasp superfamily Chalcidoidea. We tested the function of those ankyrin-encoding genes expressed along the DV axis and found that they participate in early embryonic DV patterning. We also developed a new wasp model system (Melittobia) and found that some functional integration of ankyrin genes have been preserved for over 90 million years.ConclusionsOur results indicate that regulatory networks can incorporate novel genes that then become necessary for stable and repeatable outputs. Even a modest role in developmental networks may be enough to allow novel or duplicate genes to be maintained in the genome and become fully integrated network components.