Applications of comparative evolution to human disease genetics

McWhite, Claire D.; Liebeskind, Benjamin J.; Marcotte, Edward M.

doi:10.1016/j.gde.2015.08.004

Cited by 7 publications

(4 citation statements)

References 91 publications

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“…The meeting also featured several algorithmic contributions. Of particular note was work presented by Benjamin Liebeskind and Claire McWhite (University of Texas at Austin, USA) that leveraged conserved protein networks to better discern between paralogs and orthologs, focusing on networks that are involved in or associated with human diseases ( Liebeskind, 2016 ; McWhite et al , 2015 ). Similarly Klaas Vandepoele (University of Ghent – VIB, Belgium) compares gene expression level commonalities across different plant species to gain additional insight for correctly identifying functionally conserved (co-) orthologs showing conserved spatial-temporal expression ( Movahedi et al , 2012 ; Tzfadia et al , 2016 ).…”

Section: Algorithmic Advancesmentioning

confidence: 99%

Gearing up to handle the mosaic nature of life in the quest for orthologs

et al. 2017

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Summary: The Quest for Orthologs (QfO) is an open collaboration framework for experts in comparative phylogenomics and related research areas who have an interest in highly accurate orthology predictions and their applications. We here report highlights and discussion points from the QfO meeting 2015 held in Barcelona. Achievements in recent years have established a basis to support developments for improved orthology prediction and to explore new approaches. Central to the QfO effort is proper benchmarking of methods and services, as well as design of standardized datasets and standardized formats to allow sharing and comparison of results. Simultaneously, analysis pipelines have been improved, evaluated and adapted to handle large datasets. All this would not have occurred without the long-term collaboration of Consortium members. Meeting regularly to review and coordinate complementary activities from a broad spectrum of innovative researchers clearly benefits the community. Highlights of the meeting include addressing sources of and legitimacy of disagreements between orthology calls, the context dependency of orthology definitions, special challenges encountered when analyzing very anciently rooted orthologies, orthology in the light of whole-genome duplications, and the concept of orthologous versus paralogous relationships at different levels, including domain-level orthology. Furthermore, particular needs for different applications (e.g. plant genomics, ancient gene families and others) and the infrastructure for making orthology inferences available (e.g. interfaces with model organism databases) were discussed, with several ongoing efforts that are expected to be reported on during the upcoming 2017 QfO meeting.

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Section: Algorithmic Advancesmentioning

confidence: 99%

Gearing up to handle the mosaic nature of life in the quest for orthologs

et al. 2017

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“…Applying a simple hypothesis to a multifactorial problem delays progress in understanding the etiology and development of applicable tests; for example, this type of approach significantly delayed understanding the etiology of atherosclerosis. 10 The Comparative Approach McWhite et al 24 provide a recent review on the comparative approach and its application to human disease research, including advances in technique that can be used to elucidate and understand PQ neurotoxicity. The multifactorial approach is complementary to the comparative approach.…”

Section: Part I: Laboratory Context Animal Modelsmentioning

confidence: 99%

Multifactorial theory applied to the neurotoxicity of paraquat and paraquat-induced mechanisms of developing Parkinson's disease

Zhang

Thompson

2016

Laboratory Investigation

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Laboratory studies involving repeated exposure to paraquat (PQ) in different animal models can induce many of the pathological features of Parkinson's disease (PD), such as the loss of dopaminergic neurons in the nigrostriatal dopamine system. Epidemiological studies identify an increased risk of developing PD in human populations living in areas where PQ exposure is likely to occur and among workers lacking appropriate protective equipment. The mechanisms involved in developing PD may not be due to any single cause, but rather a multifactorial situation may exist where PQ exposure may cause PD in some circumstances. Multifactorial theory is adopted into this review that includes a number of sub-cellular mechanisms to explain the pathogenesis of PD. The theory is placed into an environmental context of chronic low-dose exposure to PQ that consequently acts as an oxidative stress inducer. Oxidative stress and the metabolic processes of PQ-inducing excitotoxicity, α-synuclein aggregate formation, autophagy, alteration of dopamine catabolism, and inactivation of tyrosine hydroxylase are positioned as causes for the loss of dopaminergic cells. The environmental context and biochemistry of PQ in soils, water, and organisms is also reviewed to identify potential routes that can lead to chronic rates of low-dose exposure that would replicate the type of response that is observed in animal models, epidemiological studies, and other types of laboratory investigations involving PQ exposure. The purpose of this review is to synthesize key relations and summarize hypotheses linking PD to PQ exposure by using the multifactorial approach. Recommendations are given to integrate laboratory methods to the environmental context as a means to improve on experimental design. The multifactorial approach is necessary for conducting valid tests of causal relations, for understanding of potential relations between PD and PQ exposure, and may prevent further delay in solving what has proven to be an evasive etiological problem.

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“… McGary et al (2010) found many such associations, discovering equivalent gene modules involved in human diseases and mutant phenotypes in model organisms ( ). Additionally, better predictions should emerge as more GI data from model organisms, particularly higher eukaryotes, are obtained ( Golden, 2017 ; McWhite et al, 2015 ; Woods et al, 2013 ).…”

Section: Using Model Organisms To Discover Gene–phenotype Association...mentioning

confidence: 99%

Humanized yeast to model human biology, disease and evolution

Kachroo

Vandeloo

Greco

et al. 2022

Disease Models &Amp; Mechanisms

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For decades, budding yeast, a single-cellular eukaryote, has provided remarkable insights into human biology. Yeast and humans share several thousand genes despite morphological and cellular differences and over a billion years of separate evolution. These genes encode critical cellular processes, the failure of which in humans results in disease. Although recent developments in genome engineering of mammalian cells permit genetic assays in human cell lines, there is still a need to develop biological reagents to study human disease variants in a high-throughput manner. Many protein-coding human genes can successfully substitute for their yeast equivalents and sustain yeast growth, thus opening up doors for developing direct assays of human gene function in a tractable system referred to as ‘humanized yeast’. Humanized yeast permits the discovery of new human biology by measuring human protein activity in a simplified organismal context. This Review summarizes recent developments showing how humanized yeast can directly assay human gene function and explore variant effects at scale. Thus, by extending the ‘awesome power of yeast genetics’ to study human biology, humanizing yeast reinforces the high relevance of evolutionarily distant model organisms to explore human gene evolution, function and disease.

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Applications of comparative evolution to human disease genetics

Cited by 7 publications

References 91 publications

Gearing up to handle the mosaic nature of life in the quest for orthologs

Gearing up to handle the mosaic nature of life in the quest for orthologs

Multifactorial theory applied to the neurotoxicity of paraquat and paraquat-induced mechanisms of developing Parkinson's disease

Humanized yeast to model human biology, disease and evolution

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