Meta Analysis of Human AlzGene Database: Benefits and Limitations of Using C. elegans for the Study of Alzheimer's Disease and Co-morbid Conditions

Nia, Behrad Vahdati; Kang, Christine; Tran, Michelle G.; Lee, Dong Hoon; Murakami, Shin

doi:10.3389/fgene.2017.00055

Cited by 22 publications

(51 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the 751 publications, 569 articles were from PubMed and 182 articles were from Scopus. Importantly, ACE, TNF, and MTHFR were found to be risk factor genes in other neurological disorders, including ALS (Amyotrophic Lateral Sclerosis), MS (Multiple Sclerosis), PD (Parkinson's Disease), and Schizophrenia [1]. Table 2 confirms that our previous study is the first report of the three AD genes associated with Alzheimer's disease (Table 2).…”

Section: Resultssupporting

confidence: 80%

“…Over the past decade, only several genes are known to be associated with AD. Three of those AD genes (ACE, MTHFR, and TNF) are associated with multiple neurological disorders [1], the result of which also suggest three major ontology pathways but not limited to, lipoprotein metabolism, hemostasis and extracellular organizations. The common GWAS hits for AD are also hits in other diseases is evidence of complex gene interactions.…”

Section: Discussionmentioning

confidence: 99%

“…Meta-analysis was performed as described previously [1]. To compare the previous data, publications from January 1, 2013 to April 15, 2017 were investigated from the PubMed database and Scopus to evaluate the genes that are associated with Alzheimer's disease.…”

Section: Methodsmentioning

confidence: 99%

“…The genetic factors contribute to the predisposition of the disease with multiple genes playing a role. Although the most wellcharacterized LOAD gene is the apolipoprotein E (APOE) gene, the genome-wide association studies and other linkage analysis identified more than 100 genes [1,6], which remain to be investigated.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Evidence-Based Genetics and Identification of Key Human Alzheimer’s Disease Alleles with Co-morbidities

Le¹,

Crouch²,

Villanueva³

et al. 2020

J Neurol Exp Neurosci

Self Cite

View full text Add to dashboard Cite

Advancements in biomedical research have contributed to increasing the life expectancy of humans, but we now observe an increase in age-related diseases such as Alzheimer's disease. Genome-Wide Association Studies (GWAS) and linkage studies have identified human genes associated with Alzheimer's disease (referred to as AD genes). A previous study by Vahdati in 2017 has revealed the human AD genes and counterparts in model species [1]. Thus, we further investigate the co-morbidity genes and alleles. Using ontology analysis combined with cluster analysis, the study identified functional pathways enriched among the human AD genes, including 179 genes out of 695 human AD genes (26%) that were associated with one or more of the four neurological diseases including Amyotrophic lateral sclerosis, Multiple sclerosis, Parkinson's disease, and Schizophrenia [1]. More importantly, the results indicate co-morbidities with Late-Onset Alzheimer's Disease (LOAD) and other neurological conditions, implying the complexity of the phenotypes in the human AD. The co-morbidity genes may account for mixed symptoms for human AD as well as age-related risks of infections. Of them, the three genes are well conserved (Angiotensin I Converting Enzyme gene, ACE; Methylenetetrahydrofolate Reductase gene, MTHFR; and tumor necrosis factor gene, TNF). In this study, we confirmed the comorbidity of the three genes associated with AD. We further identified the comorbidity of two alleles in the MTHFR gene, C677T and A222V, significantly associated with Alzheimer's disease. This study provides an example of evidencebased analysis that is cost-effective and may be an effective approach to develop cure-alls for multiple diseases.

show abstract

Section: Resultssupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evidence-Based Genetics and Identification of Key Human Alzheimer’s Disease Alleles with Co-morbidities

Le¹,

Crouch²,

Villanueva³

et al. 2020

J Neurol Exp Neurosci

Self Cite

View full text Add to dashboard Cite

show abstract

“…Subsequently, we created a minimal, unpublished, online tool distributed through informal C. elegans community channels to enhance its accessibility and utility. OrthoList has indeed both facilitated the identification of orthology (e.g., Firnhaber and Hammarlund 2013;Du et al 2015;Vahdati Nia et al 2017) and has been used as the basis for streamlining RNAi screens (e.g., Gillard et al 2015;Hernando-Rodríguez et al 2018;Nordquist et al 2018).…”

Section: )mentioning

confidence: 99%

OrthoList 2: A New Comparative Genomic Analysis of Human and Caenorhabditis elegans Genes

et al. 2018

View full text Add to dashboard Cite

OrthoList, a compendium of Caenorhabditis elegans genes with human orthologs compiled in 2011 by a meta-analysis of four orthology-prediction methods, has been a popular tool for identifying conserved genes for research into biological and disease mechanisms. However, the efficacy of orthology prediction depends on the accuracy of gene-model predictions, an ongoing process, and orthology-prediction algorithms have also been updated over time. Here we present OrthoList 2 (OL2), a new comparative genomic analysis between C. elegans and humans, and the first assessment of how changes over time affect the landscape of predicted orthologs between two species. Although we find that updates to the orthology-prediction methods significantly changed the landscape of C. elegans-human orthologs predicted by individual programs and-unexpectedly-reduced agreement among them, we also show that our meta-analysis approach "buffered" against changes in gene content. We show that adding results from more programs did not lead to many additions to the list and discuss reasons to avoid assigning "scores" based on support by individual orthology-prediction programs; the treatment of "legacy" genes no longer predicted by these programs; and the practical difficulties of updating due to encountering deprecated, changed, or retired gene identifiers. In addition, we consider what other criteria may support claims of orthology and alternative approaches to find potential orthologs that elude identification by these programs. Finally, we created a new web-based tool that allows for rapid searches of OL2 by gene identifiers, protein domains [InterPro and SMART (Simple Modular Architecture Research Tool], or human disease associations ([OMIM (Online Mendelian Inheritence in Man], and also includes available RNA-interference resources to facilitate potential translational cross-species studies. KEYWORDS genome; homology; Caenorhabditis elegans; human S TUDIES in Caenorhabditis elegans have illuminated many mechanisms relevant to human biology and disease. Forward genetic screens based on phenotype have identified genes homologous to human disease-associated genes, illuminating fundamental properties about their roles and mechanisms of action (e.g., Greenwald 2012; Sundaram 2013; Golden 2017; van der Bliek et al. 2017). Reverse genetic methods have expanded the repertoire of possible genetic approaches. These methods include the ability to phenocopy loss-of-function mutations by feeding worms bacteria expressing double-stranded RNA (Fire et al. 1998; Timmons and Fire 1998). The efficiency of RNA interference (RNAi) in C. elegans has allowed for genome-wide screens (Fraser et al. 2000; Kamath et al. 2003; O'Reilly et al. 2016), or screens targeted to specific conserved genes, such as human disease genes (e.g., Sin et al. 2014; Vahdati Nia et al. 2017; Nordquist et al. 2018) or those involved in fundamental biological processes (e.g., Balklava et al. 2007; Dunn et al. 2010; Firnhaber and Hammarlund 2013; Allen et al. 2014; Du et al. 2015). Other...

show abstract

Genetic and Pharmacological Discovery for Alzheimer’s Disease Using Caenorhabditis elegans

Griffin

Caldwell

2017

ACS Chem. Neurosci.

View full text Add to dashboard Cite

The societal burden presented by Alzheimer's disease warrants both innovative and expedient means by which its underlying molecular causes can be both identified and mechanistically exploited to discern novel therapeutic targets and strategies. The conserved characteristics, defined neuroanatomy, and advanced technological application of Caenorhabditis elegans render this metazoan an unmatched tool for probing neurotoxic factors. In addition, its short lifespan and importance in the field of aging make it an ideal organism for modeling age-related neurodegenerative disease. As such, this nematode system has demonstrated its value in predicting functional modifiers of human neurodegenerative disorders. Here, we review how C. elegans has been utilized to model Alzheimer's disease. Specifically, we present how the causative neurotoxic peptides, amyloid-β and tau, contribute to disease-like neurodegeneration in C. elegans and how they translate to human disease. Furthermore, we describe how a variety of transgenic animal strains, each with distinct utility, have been used to identify both genetic and pharmacological modifiers of toxicity in C. elegans. As technological advances improve the prospects for intervention, the rapidity, unparalleled accuracy, and scale that C. elegans offers researchers for defining functional modifiers of neurodegeneration should speed the discovery of improved therapies for Alzheimer's disease.

show abstract

Meta Analysis of Human AlzGene Database: Benefits and Limitations of Using C. elegans for the Study of Alzheimer's Disease and Co-morbid Conditions

Cited by 22 publications

References 26 publications

Evidence-Based Genetics and Identification of Key Human Alzheimer’s Disease Alleles with Co-morbidities

Evidence-Based Genetics and Identification of Key Human Alzheimer’s Disease Alleles with Co-morbidities

OrthoList 2: A New Comparative Genomic Analysis of Human and Caenorhabditis elegans Genes

Genetic and Pharmacological Discovery for Alzheimer’s Disease Using Caenorhabditis elegans

Contact Info

Product

Resources

About