ArticlePLoS genetics2013
Genome-wide association mapping in dogs enables identification of the homeobox gene, NKX2-8, as a genetic component of neural tube defects in humans.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 40 citations in OpenAlex.
- Congenital and Breed-Associated Vertebral Anomalies in Dogs and Cats: Developmental Anatomy, Genetic Determinants, and Biological Significance.Life (Basel, Switzerland) · 2026Review
- Case Report: Surgical management of a meningomyelocele in a cat.Frontiers in veterinary science · 2026Article
- EFNB3 Frameshift Variant in Weimaraner Dogs with a Condition Resembling a Congenital Mirror Movement Disorder.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Anencephaly and palatoschisis in 2 newborn puppies.The Canadian veterinary journal = La revue veterinaire canadienne · 2025Article
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- HomozygousGenes · 2024Article
- Cell type specializations of the vocal-motor cortex in songbirds.Cell reports · 2023Article
- An Overview of Canine Inherited Neurological Disorders with Known Causal Variants.Animals : an open access journal from MDPI · 2023Review
- BRASS: Permutation methods for binary traits in genetic association studies with structured samples.PLoS genetics · 2023Article
- NK2 homeobox gene cluster: Functions and roles in human diseases.Genes & diseases · 2023Review
- Neurogenic Bladder in Dogs, Cats and Humans: A Comparative Review of Neurological Diseases.Animals : an open access journal from MDPI · 2022Review
- Identification of the Key Regulators of Spina Bifida Through Graph-Theoretical Approach.Frontiers in genetics · 2021Article
- Quality of DNA extracted from formalin-fixed, paraffin-embedded canine tissues.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2020Article
- Genetic analysis of optic nerve head coloboma in the Nova Scotia Duck Tolling Retriever identifies discordance with the NHEJ1 intronic deletion (collie eye anomaly mutation).Veterinary ophthalmology · 2018Article
- Species-Specific 5 mC and 5 hmC Genomic Landscapes Indicate Epigenetic Contribution to Human Brain Evolution.Frontiers in molecular neuroscience · 2018Article
- Evaluation of the genetic basis of primary hypoadrenocorticism in Standard Poodles using SNP array genotyping and whole-genome sequencing.Mammalian genome : official journal of the International Mammalian Genome Society · 2017Article
- Shared molecular networks in orofacial and neural tube development.Birth defects research · 2017Article
- Spina Bifida: Pathogenesis, Mechanisms, and Genes in Mice and Humans.Scientifica · 2017Review
- An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed.G3 (Bethesda, Md.) · 2016Article
- Fetal diffusion tensor quantification of brainstem pathology in Chiari II malformation.European radiology · 2016Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Neural tube defects (NTDs) is a general term for central nervous system malformations secondary to a failure of closure or development of the neural tube. The resulting pathologies may involve the brain, spinal cord and/or vertebral column, in addition to associated structures such as soft tissue or skin. The condition is reported among the more common birth defects in humans, leading to significant infant morbidity and mortality. The etiology remains poorly understood but genetic, nutritional, environmental factors, or a combination of these, are known to play a role in the development of NTDs. The variable conditions associated with NTDs occur naturally in dogs, and have been previously reported in the Weimaraner breed. Taking advantage of the strong linkage-disequilibrium within dog breeds we performed genome-wide association analysis and mapped a genomic region for spinal dysraphism, a presumed NTD, using 4 affected and 96 unaffected Weimaraners. The associated region on canine chromosome 8 (pgenome =3.0 × 10(-5)), after 100,000 permutations, encodes 18 genes, including NKX2-8, a homeobox gene which is expressed in the developing neural tube. Sequencing NKX2-8 in affected Weimaraners revealed a G to AA frameshift mutation within exon 2 of the gene, resulting in a premature stop codon that is predicted to produce a truncated protein. The exons of NKX2-8 were sequenced in human patients with spina bifida and rare variants (rs61755040 and rs10135525) were found to be significantly over-represented (p=0.036). This is the first documentation of a potential role for NKX2-8 in the etiology of NTDs, made possible by investigating the molecular basis of naturally occurring mutations in dogs.
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