ArticleDevelopment (Cambridge, England)2012
Rapid positional cloning of zebrafish mutations by linkage and homozygosity mapping using whole-genome sequencing.
Article in Development (Cambridge, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
62 citing papers in PubMed, 97 citations in OpenAlex.
- A single-cell transcriptomic atlas of inner ear morphogenesis in zebrafish.bioRxiv : the preprint server for biology · 2025Article
- Characterisation of lmx1b paralogues in zebrafish reveals divergent roles in skeletal, kidney and muscle development.Biology open · 2025Article
- Phenotype to genotype: A new and rapid approach using whole-genome sequencing.PLoS genetics · 2025Article
- Development of the semicircular canals and otolithic organs of the vertebrate inner ear.Current topics in developmental biology · 2025Review
- Versican controlled by Lmx1b regulates hyaluronate density and hydration for semicircular canal morphogenesis.Development (Cambridge, England) · 2025Article
- Versican controlled by Lmx1b regulates hyaluronate density and hydration for semicircular canal morphogenesis.bioRxiv : the preprint server for biology · 2024Article
- Importin 13-dependent axon diameter growth regulates conduction speeds along myelinated CNS axons.Nature communications · 2024Article
- Exploring hematopoiesis in zebrafish using forward genetic screening.Experimental & molecular medicine · 2024Review
- Bacteriophage-based techniques for elucidating the function of zebrafish gut microbiota.Applied microbiology and biotechnology · 2023Review
- Review
- Gene-alcohol interactions in birth defects.Current topics in developmental biology · 2023Article
- A combinatorial strategy to identify various types of QTLs for quantitative traits using extreme phenotype individuals in an FPlant communications · 2022Article
- Translational relevance of forward genetic screens in animal models for the study of psychiatric disease.Neuroscience and biobehavioral reviews · 2022Review
- Allele-specific gene expression can underlie altered transcript abundance in zebrafish mutants.eLife · 2022Article
- Genetic landscape of T cells identifies synthetic lethality for T-ALL.Communications biology · 2021Article
- A fish is not a mouse: understanding differences in background genetics is critical for reproducibility.Lab animal · 2021Review
- Easymap: A User-Friendly Software Package for Rapid Mapping-by-Sequencing of Point Mutations and Large Insertions.Frontiers in plant science · 2021Article
- Small fish, big prospects: using zebrafish to unravel the mechanisms of hereditary hearing loss.Hearing research · 2020Article
- ACells · 2020Article
- Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b.The Journal of cell biology · 2020Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Forward genetic screens in zebrafish have identified >9000 mutants, many of which are potential disease models. Most mutants remain molecularly uncharacterized because of the high cost, time and labor investment required for positional cloning. These costs limit the benefit of previous genetic screens and discourage future screens. Drastic improvements in DNA sequencing technology could dramatically improve the efficiency of positional cloning in zebrafish and other model organisms, but the best strategy for cloning by sequencing has yet to be established. Using four zebrafish inner ear mutants, we developed and compared two approaches for 'cloning by sequencing': one based on bulk segregant linkage (BSFseq) and one based on homozygosity mapping (HMFseq). Using BSFseq we discovered that mutations in lmx1b and jagged1b cause abnormal ear morphogenesis. With HMFseq we validated that the disruption of cdh23 abolishes the ear's sensory functions and identified a candidate lesion in lhfpl5a predicted to cause nonsyndromic deafness. The success of HMFseq shows that the high intrastrain polymorphism rate in zebrafish eliminates the need for time-consuming map crosses. Additionally, we analyzed diversity in zebrafish laboratory strains to find areas of elevated diversity and areas of fixed homozygosity, reinforcing recent findings that genome diversity is clustered. We present a database of >15 million sequence variants that provides much of this approach's power. In our four test cases, only a single candidate single nucleotide polymorphism (SNP) remained after subtracting all database SNPs from a mutant's critical region. The saturation of the common SNP database and our open source analysis pipeline MegaMapper will improve the pace at which the zebrafish community makes unique discoveries relevant to human health.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.