scholarly journals Genetic control of male production in Daphnia pulex

2019 ◽  
Vol 116 (31) ◽  
pp. 15602-15609 ◽  
Author(s):  
Zhiqiang Ye ◽  
Cécile Molinier ◽  
Chaoxian Zhao ◽  
Christoph R. Haag ◽  
Michael Lynch
Keyword(s):  
Single Gene ◽  
Daphnia Pulex ◽  
Environmental Cues ◽  
Cyclical Parthenogenesis ◽  
Methyl Farnesoate ◽  
Expression Change ◽  
Protein Coding ◽  
Offspring Sex ◽  
Different Populations ◽  
Chromosome I

Daphnia normally reproduce by cyclical parthenogenesis, with offspring sex being determined by environmental cues. However, some females have lost the ability to produce males. Our results demonstrate that this loss of male-producing ability is controlled by a dominant allele at a single locus. We identified the locus by comparing whole-genome sequences of 67 nonmale-producing (NMP) and 100 male-producing (MP) clones from 5 Daphnia pulex populations, revealing 132 NMP-linked SNPs and 59 NMP-linked indels within a single 1.1-Mb nonrecombining region on chromosome I. These markers include 7 nonsynonymous mutations, all of which are located within one unannotated protein-coding gene (gene 8960). Within this single gene, all of the marker-linked NMP haplotypes from different populations form a monophyletic clade, suggesting a single origin of the NMP phenotype, with the NMP haplotype originating by introgression from a sister species, Daphnia pulicaria. Methyl farnesoate (MF) is the innate juvenile hormone in daphnids, which induces the production of males and whose inhibition results in female-only production. Gene 8960 is sensitive to treatment by MF in MP clones, but such responsiveness is greatly reduced in NMP clones. Thus, we hypothesize that gene 8960 is located downstream of the MF-signaling pathway in D. pulex, with the NMP phenotype being caused by expression change of gene 8960.

scholarly journals Genome Editing Human Pluripotent Stem Cells to Model β-Cell Disease and Unmask Novel Genetic Modifiers

2021 ◽  
Vol 12 ◽  
Author(s):  
Matthew N. George ◽  
Karla F. Leavens ◽  
Paul Gadue
Keyword(s):  
Stem Cells ◽  
Genome Editing ◽  
Pluripotent Stem Cells ◽  
Genetic Disease ◽  
Single Gene ◽  
Monogenic Diabetes ◽  
Human Pluripotent Stem Cells ◽  
Genetic Modifiers ◽  
Β Cell ◽  
Protein Coding

A mechanistic understanding of the genetic basis of complex diseases such as diabetes mellitus remain elusive due in large part to the activity of genetic disease modifiers that impact the penetrance and/or presentation of disease phenotypes. In the face of such complexity, rare forms of diabetes that result from single-gene mutations (monogenic diabetes) can be used to model the contribution of individual genetic factors to pancreatic β-cell dysfunction and the breakdown of glucose homeostasis. Here we review the contribution of protein coding and non-protein coding genetic disease modifiers to the pathogenesis of diabetes subtypes, as well as how recent technological advances in the generation, differentiation, and genome editing of human pluripotent stem cells (hPSC) enable the development of cell-based disease models. Finally, we describe a disease modifier discovery platform that utilizes these technologies to identify novel genetic modifiers using induced pluripotent stem cells (iPSC) derived from patients with monogenic diabetes caused by heterozygous mutations.

scholarly journals Association study of RS535296987 in TEX14 gene in azoospermiamen: RFLP and DNA sequencing

Genetika ◽  
2021 ◽  
Vol 53 (2) ◽  
pp. 729-737
Author(s):  
Mohammad Vahedi ◽  
Masoud Sheidai
Keyword(s):  
Dna Sequencing ◽  
Dna Sequences ◽  
Chromosome 17 ◽  
Protein Coding ◽  
Nucleotide Variability ◽  
Functional Studies ◽  
Low Degree ◽  
Different Populations ◽  
Human Chromosome 17 ◽  
And Control

Azoospermia is one of the kinds of male infertility, with clinically the most severe phenotype as the natural conception cannot occur. It has been estimated to affect 0.1 to 1% of all men and 10-15% of men in infertile couples. TEX14 (Testis expressed 14, intercellular bridge forming factor) is a protein coding gene, which is located in human chromosome 17, (17q22). Tex14 gene appears to be crucial for perfect spermatogenesis and functional studies indicate the role of TEX14 in the intercellular bridges between developing male germ cells. The gene contains 32 exons and spans 137 kb. A heterogeneousresultis available on the association TEX14 gene and azoospermia. Therefore, it is suggested to investigate this gene in different populations. We analyzed about 200 men in two categories of azoospermia and healthy persons by RFLP as well as DNA sequencing to indicate an association between rs535296987 in TEX14 and its adjacent nucleotides to azoospermia. We found no significant association based on RFLP data and also by clustering of case and control specimens based on DNA sequencing. In general, a low level of nucleotide variability was observed in DNA sequences. Therefore, both eternity in the studied samples and low degree of mutations in this genetic region, may be the reason for heterogeneous reports on association of TEX14 and azoospermia.

scholarly journals A health disparities study of MicroRNA-146a expression in prostate cancer samples derived from African American and European American patients

2020 ◽  
Vol 10 (2) ◽  
pp. 1
Author(s):  
Monet Stevenson ◽  
Narendra Narendra Banerjee ◽  
Narendra Banerjee ◽  
Kuldeep Rawat ◽  
Lin Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Association Studies ◽  
Single Gene ◽  
Micro Rna ◽  
Genome Wide Association Studies ◽  
Racial Groups ◽  
Protein Coding ◽  
Rna Molecules ◽  
Prostate Carcinogenesis

Considering the prevalence of prostate cancer all over the world, it is desired to have tools, technologies, and biomarkers which help in early detection of the disease and discriminate different races and ethnic groups. Genetic information from the single gene analysis and genome-wide association studies have identified few biomarkers, however, the drivers of prostate cancer remain unknown in the majority of prostate cancer patients. In those cases where genetic association has been identified, the genes confer only a modest risk of this cancer, hence, making them less relevant for risk counseling and disease management. There is a need for additional biomarkers for diagnosis and prognosis of prostate cancer. MicroRNAs are a class of non-protein coding RNA molecules that are frequently dysregulated in different cancers including prostate cancer and show promise as diagnostic biomarkers and targets for therapy. Here we describe the role of micro RNA 146a (miR-146a) which may serve as a diagnostic and prognostic marker for prostate cancer, as indicated from the data presented in this report. Also, a pilot study indicated differential expression of miR-146a in prostate cancer cell lines and tissues from different racial groups. Reduced expression of miR-146a was observed in African American tumor tissues compared to those from European Whites This report provides a novel insight into understanding the prostate carcinogenesis.

The molecular systematics of blowflies and screwworm flies (Diptera: Calliphoridae) using 28S rRNA, COX1 and EF-1α: insights into the evolution of dipteran parasitism

Parasitology ◽  
2011 ◽  
Vol 138 (13) ◽  
pp. 1760-1777 ◽  
Author(s):  
LAURA M. McDONAGH ◽  
JAMIE R. STEVENS
Keyword(s):  
Sequence Data ◽  
Single Gene ◽  
Nuclear Gene ◽  
Evolutionary Status ◽  
28S Rrna ◽  
Gene Trees ◽  
Data Set ◽  
Protein Coding ◽  
Nucleotide Sequence Data ◽  
The Family

SUMMARYThe Calliphoridae include some of the most economically significant myiasis-causing flies in the world – blowflies and screwworm flies – with many being notorious for their parasitism of livestock. However, despite more than 50 years of research, key taxonomic relationships within the family remain unresolved. This study utilizes nucleotide sequence data from the protein-coding genes COX1 (mitochondrial) and EF1α (nuclear), and the 28S rRNA (nuclear) gene, from 57 blowfly taxa to improve resolution of key evolutionary relationships within the family Calliphoridae. Bayesian phylogenetic inference was carried out for each single-gene data set, demonstrating significant topological difference between the three gene trees. Nevertheless, all gene trees supported a Calliphorinae-Luciliinae subfamily sister-lineage, with respect to Chrysomyinae. In addition, this study also elucidates the taxonomic and evolutionary status of several less well-studied groups, including the genus Bengalia (either within Calliphoridae or as a separate sister-family), genus Onesia (as a sister-genera to, or sub-genera within, Calliphora), genus Dyscritomyia and Lucilia bufonivora, a specialised parasite of frogs and toads. The occurrence of cross-species hybridisation within Calliphoridae is also further explored, focusing on the two economically significant species Lucilia cuprina and Lucilia sericata. In summary, this study represents the most comprehensive molecular phylogenetic analysis of family Calliphoridae undertaken to date.

scholarly journals Different Domains of Phytophthora sojae Effector Avr4/6 Are Recognized by Soybean Resistance Genes Rps4 and Rps6

2010 ◽  
Vol 23 (4) ◽  
pp. 425-435 ◽  
Author(s):  
Daolong Dou ◽  
Shiv D. Kale ◽  
Tingli Liu ◽  
Qinghua Tang ◽  
Xia Wang ◽  
...  
Keyword(s):  
Protein Translocation ◽  
Single Gene ◽  
Phytophthora Sojae ◽  
Avirulence Genes ◽  
Coding Region ◽  
Nucleotide Substitutions ◽  
Protein Coding ◽  
C Terminus ◽  
Oomycete Pathogen ◽  
Soybean Leaves

At least 12 avirulence genes have been genetically identified and mapped in Phytophthora sojae, an oomycete pathogen causing root and stem rot of soybean. Previously, the Avr4 and Avr6 genes of P. sojae were genetically mapped within a 24 kb interval of the genome. Here, we identify Avr4 and Avr6 and show that they are actually a single gene, Avr4/6, located near the 24-kb region. Avr4/6 encodes a secreted protein of 123 amino acids with an RXLR-dEER protein translocation motif. Transient expression of Avr4/6 in soybean leaves revealed that its gene product could trigger a hypersensitive response (HR) in the presence of either Rps4 or Rps6. Silencing Avr4/6 in P. sojae stable transformants abolished the avirulence phenotype exhibited on both Rps4 and Rps6 soybean cultivars. The N terminus of Avr4/6, including the dEER motif, is sufficient to trigger Rps4-dependent HR while its C terminus is sufficient to trigger Rps6-mediated HR. Compared with alleles from avirulent races, alleles of Avr4/6 from virulent races possess nucleotide substitutions in the 5′ untranslated region of the gene but not in the protein-coding region.

scholarly journals Convergent and distributed effects of the schizophrenia-associated 3q29 deletion on the human neural transcriptome

2020 ◽  
Author(s):  
Esra Sefik ◽  
Ryan H. Purcell ◽  
Elaine F. Walker ◽  
Gary J. Bassell ◽  
Jennifer G. Mulle ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Single Gene ◽  
Normal Function ◽  
Cellular Functions ◽  
Protein Coding ◽  
Post Translational Modifications ◽  
Increased Risk ◽  
Disease Associations ◽  
Guilt By Association ◽  
The Impact

AbstractThe 3q29 deletion (3q29Del) confers >40-fold increased risk for schizophrenia. However, no single gene in this interval is definitively associated with disease, prompting the hypothesis that neuropsychiatric sequelae emerge upon loss of multiple functionally-connected genes. 3q29 genes are unevenly annotated and the impact of 3q29Del on the human neural transcriptome is unknown. To systematically formulate unbiased hypotheses about molecular mechanisms linking 3q29Del to neuropsychiatric illness, we conducted a systems-level network analysis of the non-pathological adult human cortical transcriptome and generated evidence-based predictions that relate 3q29 genes to novel functions and disease associations. The 21 protein-coding genes located in the interval segregated into seven clusters of highly co-expressed genes, demonstrating both convergent and distributed effects of 3q29Del across the interrogated transcriptomic landscape. Pathway analysis of these clusters indicated involvement in nervous-system functions, including synaptic signaling and organization, as well as core cellular functions, including transcriptional regulation, post-translational modifications, chromatin remodeling and mitochondrial metabolism. Top network-neighbors of 3q29 genes showed significant overlap with known schizophrenia, autism and intellectual disability-risk genes, suggesting that 3q29Del biology is relevant to idiopathic disease. Leveraging “guilt by association”, we propose nine 3q29 genes, including one hub gene, as prioritized drivers of neuropsychiatric risk. These results provide testable hypotheses for experimental analysis on causal drivers and mechanisms of the largest known genetic risk factor for schizophrenia and highlight the study of normal function in non-pathological post-mortem tissue to further our understanding of psychiatric genetics, especially for rare syndromes like 3q29Del, where access to neural tissue from carriers is unavailable or limited.

scholarly journals Open Targets Genetics: An open approach to systematically prioritize causal variants and genes at all published human GWAS trait-associated loci

2020 ◽  
Author(s):  
Edward Mountjoy ◽  
Ellen M. Schmidt ◽  
Miguel Carmona ◽  
Gareth Peat ◽  
Alfredo Miranda ◽  
...  
Keyword(s):  
Complex Traits ◽  
Drug Targets ◽  
Association Studies ◽  
Single Gene ◽  
Cell Types ◽  
Causal Variant ◽  
Genome Wide Association Studies ◽  
Open Approach ◽  
Protein Coding ◽  
Causal Genes

AbstractGenome-wide association studies (GWAS) have identified many variants robustly associated with complex traits but identifying the gene(s) mediating such associations is a major challenge. Here we present an open resource that provides systematic fine-mapping and protein-coding gene prioritization across 133,441 published human GWAS loci. We integrate diverse data sources, including genetics (from GWAS Catalog and UK Biobank) as well as transcriptomic, proteomic and epigenomic data across many tissues and cell types. We also provide systematic disease-disease and disease-molecular trait colocalization results across 92 cell types and tissues and identify 729 loci fine-mapped to a single coding causal variant and colocalized with a single gene. We trained a machine learning model using the fine mapped genetics and functional genomics data using 445 gold standard curated GWAS loci to distinguish causal genes from background genes at the same loci, outperforming a naive distance based model. Genes prioritized by our model are enriched for known approved drug targets (OR = 8.1, 95% CI: [5.7, 11.5]). These results will be regularly updated and are publicly available through a web portal, Open Targets Genetics (OTG, http://genetics.opentargets.org), enabling users to easily prioritize genes at disease-associated loci and assess their potential as drug targets.

scholarly journals Assessment of mitochondrial genomes for heterobranch gastropod phylogenetics

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rebecca M. Varney ◽  
Bastian Brenzinger ◽  
Manuel António E. Malaquias ◽  
Christopher P. Meyer ◽  
Michael Schrödl ◽  
...  
Keyword(s):  
Single Gene ◽  
Taxonomic Revision ◽  
Land Snails ◽  
Current Understanding ◽  
Evolutionary Relationships ◽  
Mitochondrial Genomes ◽  
Small Subset ◽  
Protein Coding ◽  
Weak Support ◽  
Rates Of Evolution

Abstract Background Heterobranchia is a diverse clade of marine, freshwater, and terrestrial gastropod molluscs. It includes such disparate taxa as nudibranchs, sea hares, bubble snails, pulmonate land snails and slugs, and a number of (mostly small-bodied) poorly known snails and slugs collectively referred to as the “lower heterobranchs”. Evolutionary relationships within Heterobranchia have been challenging to resolve and the group has been subject to frequent and significant taxonomic revision. Mitochondrial (mt) genomes can be a useful molecular marker for phylogenetics but, to date, sequences have been available for only a relatively small subset of Heterobranchia. Results To assess the utility of mitochondrial genomes for resolving evolutionary relationships within this clade, eleven new mt genomes were sequenced including representatives of several groups of “lower heterobranchs”. Maximum likelihood analyses of concatenated matrices of the thirteen protein coding genes found weak support for most higher-level relationships even after several taxa with extremely high rates of evolution were excluded. Bayesian inference with the CAT + GTR model resulted in a reconstruction that is much more consistent with the current understanding of heterobranch phylogeny. Notably, this analysis recovered Valvatoidea and Orbitestelloidea in a polytomy with a clade including all other heterobranchs, highlighting these taxa as important to understanding early heterobranch evolution. Also, dramatic gene rearrangements were detected within and between multiple clades. However, a single gene order is conserved across the majority of heterobranch clades. Conclusions Analysis of mitochondrial genomes in a Bayesian framework with the site heterogeneous CAT + GTR model resulted in a topology largely consistent with the current understanding of heterobranch phylogeny. However, mitochondrial genomes appear to be too variable to serve as good phylogenetic markers for robustly resolving a number of deeper splits within this clade.

scholarly journals Genetic and Physical Localization of the Gene Controlling Leaf Pigmentation Pattern in Medicago truncatula

2020 ◽  
Vol 10 (11) ◽  
pp. 4159-4165
Author(s):  
Xiaocheng Yu ◽  
Qiulin Qin ◽  
Xia Wu ◽  
Dandan Li ◽  
Shengming Yang
Keyword(s):  
Medicago Truncatula ◽  
Leaf Surface ◽  
Anthocyanin Biosynthesis ◽  
Gene Annotation ◽  
Single Gene ◽  
Biosynthesis Pathway ◽  
Dominant Trait ◽  
Morphological Marker ◽  
Protein Coding ◽  
Protein Coding Genes

In Medicago truncatula, some ecotypes form a black or purple stain in the middle of adaxial leaf surface due to accumulation of anthocyanins. However, this morphological marker is missing in some other ecotypes, although anthocyanin biosynthesis pathway is not disrupted. Genetic analysis indicated that the lack of the leaf spot of anthocyanins accumulation is a dominant trait, which is controlled by a single gene, LPP1. Genetic mapping indicated that the LPP1 gene was delimited to a 280 kb-region on Chromosome 7. A total of 8 protein-coding genes were identified in the LPP1 locus through gene annotation and sequence analysis. Of those, two genes, putatively encoding MYB-transcriptional suppressors, were selected as candidates for functional validation.

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