Allele, phenotype and disease data at Mouse Genome Informatics: improving access and analysis

Bello, Susan M.; Smith, Cynthia L.; Eppig, Janan T.

doi:10.1007/s00335-015-9582-y

Cited by 33 publications

(34 citation statements)

References 33 publications

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“…This not only makes data integration difficult, but it also means that computation over the genotype–phenotype associations must be done with care. Similar issues at MGI have been described (46). In addition, since most anatomy, phenotype, and disease ontologies describe the biology of one species, it has traditionally been quite difficult to ‘map’ across species.…”

Section: Discussionsupporting

confidence: 72%

The Monarch Initiative: an integrative data and analytic platform connecting phenotypes to genotypes across species

et al. 2016

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The correlation of phenotypic outcomes with genetic variation and environmental factors is a core pursuit in biology and biomedicine. Numerous challenges impede our progress: patient phenotypes may not match known diseases, candidate variants may be in genes that have not been characterized, model organisms may not recapitulate human or veterinary diseases, filling evolutionary gaps is difficult, and many resources must be queried to find potentially significant genotype–phenotype associations. Non-human organisms have proven instrumental in revealing biological mechanisms. Advanced informatics tools can identify phenotypically relevant disease models in research and diagnostic contexts. Large-scale integration of model organism and clinical research data can provide a breadth of knowledge not available from individual sources and can provide contextualization of data back to these sources. The Monarch Initiative (monarchinitiative.org) is a collaborative, open science effort that aims to semantically integrate genotype–phenotype data from many species and sources in order to support precision medicine, disease modeling, and mechanistic exploration. Our integrated knowledge graph, analytic tools, and web services enable diverse users to explore relationships between phenotypes and genotypes across species.

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Section: Discussionsupporting

confidence: 72%

The Monarch Initiative: an integrative data and analytic platform connecting phenotypes to genotypes across species

et al. 2016

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“…For example, among genes robustly expressed in heart in human but not in mouse are 17 genes associated with heart disease. These include NKX2-6 , which causes conotruncal heart malformations in human [28] that, congruently, are not recapitulated by a mouse knockout [29]. The developmental profile of NKX2-6 in the human heart is ancestral; the heart expression was lost specifically in rodents, and this is therefore an example of a disease gene that would probably be better studied in the rabbit (Figure 3A).…”

Section: Resultsmentioning

confidence: 99%

“…Among the exceptions is CHRNA2 , a gene expressed in the human brain starting at birth that has been implicated in epilepsy [30, 31]. Once again, and congruently, this clinical phenotype is not recapitulated in the mouse knockout [29] (Figure 2B).…”

Section: Resultsmentioning

confidence: 99%

Developmental gene expression differences between humans and mammalian models

Cardoso-Moreira

Velten

Mort

et al. 2019

Preprint

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14Identifying the molecular programs underlying human organ development and how they differ from 15 those in model species will advance our understanding of human health and disease. 16 Developmental gene expression profiles provide a window into the genes underlying organ 17 development as well as a direct means to compare them across species. We use a transcriptomic 18 resource for mammalian organ development to characterize the temporal profiles of human genes 19 associated with distinct disease classes and to determine, for each human gene, the similarity of its 20 spatiotemporal expression with its orthologs in rhesus macaque, mouse, rat and rabbit. We find 21 that half of human genes differ from their mouse orthologs in their temporal trajectories. These 22 include more than 200 disease genes associated with brain, heart and liver disease, for which mouse 23 models should undergo extra scrutiny. We provide a new resource that evaluates for every human 24 gene its suitability to be modeled in different mammalian species. 25 26 27 28 42 rhesus macaques) are routinely used as models of both normal human development and human 43 disease because it is generally assumed that the genes and regulatory networks underlying 44 development are largely conserved across these species. While this is generally true, there are also 45 critical differences between species during development, which underlie the large diversity of 46 3 mammalian organ phenotypes [1-6,8]. Identifying the commonalities and differences between the 47 genetic programs underlying organ development in different mammalian species is therefore 48 paramount for assessing the translatability of knowledge obtained from mammalian models to 49 understand human health and disease. Critically, gene expression profiles can be directly compared 50 between species, especially when they are derived from matching cells/organs and developmental 51 stages. Gene expression therefore offers a direct means to evaluate similarities and differences 52 between species in organ developmental programs. While the relationship between gene 53 expression and phenotypes is not linear, identifying when and where gene expression differs 54 between humans and other species will help identify the conditions (i.e., developmental stages, 55 organs, genes) under which model species may not be well suited to model human development 56 and disease. 57 58Here, we take advantage of a developmental gene expression resource [13], which densely covers 59 the development of seven major organs in humans and other mammals, to characterize the 60 spatiotemporal profiles of human disease genes and gain new insights into the symptomatology of 61 diseases. We also determine for each human gene (including disease-associated genes) the 62 similarity of its spatiotemporal expression with that of its orthologs in mouse, rat, rabbit and rhesus 63 macaque. Our analyses and datasets therefore provide a new resource for assessing the suitability 64 of different mammalian species to model the action ...

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“…Phenotype to gene mapping in human and mouse were obtained from mouse (Bello et al 2015) and human phenotype ontology (Robinson et al 2008), respectively. The gene ontology information for domestic dog was obtained from dog gene ontology ENSEMBL (Zerbino et al 2018).…”

Section: Methodsmentioning

confidence: 99%

The Cuon Enigma: Genome survey and comparative genomics of the endangered Dhole (Cuon alpinus)

Habib

Ghaskadbi

Nigam

et al. 2018

Preprint

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35The Asiatic wild dog is an endangered monophyletic canid restricted to Asia; facing threats 36 from habitat fragmentation and other anthropogenic factors. Dholes have unique adaptations 37 as compared to other wolf-like canids for large litter size (larger number of mammae) and 38 hypercarnivory making it evolutionarily notable. Over evolutionary time, dhole and the 39 subsequent divergent wild canids have lost coat patterns found in African wild dog. Here we 40 report the first high coverage genome survey of Asiatic wild dog and mapped it with African 41 wild dog, dingo and domestic dog to assess the structural variants. We generated a total of 42 124.8 Gb data from 416140921 raw read pairs and retained 398659457 reads with 52X 43 coverage and mapped 99.16% of the clean reads to the three reference genomes. We 44 identified ~13553269 SNV's, ~2858184 InDels, ~41000 SVs, ~1854109 SSRs and about 45 1000 CNVs. We compared the annotated genome of dingo and domestic dog with dhole 46 genome sequence to understand the role of genes responsible in pelage pattern, dentition and 47 mammary glands. Positively selected genes for these phenotypes were looked for SNP 48 variants and top ranked genes for coat pattern, dentition and mammary glands were found to 49 play a role in signalling and developmental pathways. Mitochondrial genome assembly 50 predicted 35 genes, 11 CDS and 24 tRNA. This genome information will help in 51 understanding the divergence of two monophlyletic canids, Cuon and Lycaon, and the 52 evolutionary adaptations of dholes with respect to other canids. 53 54 55 56 57 58 59The Asiatic wild dog (Cuon alpinus) or dhole is monotypic canid belonging to the genus 60 Cuon. Dholes were widely distributed across the continents of North America, Europe and 61

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Allele, phenotype and disease data at Mouse Genome Informatics: improving access and analysis

Cited by 33 publications

References 33 publications

The Monarch Initiative: an integrative data and analytic platform connecting phenotypes to genotypes across species

The Monarch Initiative: an integrative data and analytic platform connecting phenotypes to genotypes across species

Developmental gene expression differences between humans and mammalian models

The Cuon Enigma: Genome survey and comparative genomics of the endangered Dhole (Cuon alpinus)

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