ArticlePLoS genetics2014
A LINE-1 insertion in DLX6 is responsible for cleft palate and mandibular abnormalities in a canine model of Pierre Robin sequence.
Article in PLoS genetics, 2014. 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, 58 citations in OpenAlex.
- Loss-of-function mutation in the X-linked TBX22 promoter disrupts an ETS-1 binding site and leads to cleft palate.Human genetics · 2015Trial
- Association of the Disheveled 2 (DVL2) Gene c.2044delC Variant with Increased Risk of Canine Cleft Palate.Animal genetics · 2026Article
- Genomic analyses identify 15 risk loci and revealProceedings of the National Academy of Sciences of the United States of America · 2025Article
- A naturally occurring canine model of syndromic congenital microphthalmia.G3 (Bethesda, Md.) · 2024Article
- Cleft Lip and Palate in Four Full-Sib Puppies from a Single Litter of Staffordshire Bull Terrier Dogs: An Anatomical and Genetic Study.Animals : an open access journal from MDPI · 2023Article
- Chloroquine regulates the proliferation and apoptosis of palate development on mice embryo by activating P53 through blocking autophagy in vitro.In vitro cellular & developmental biology. Animal · 2022Article
- Brachygnathia Inferior in Cloned Dogs Is Possibly Correlated with Variants of Wnt Signaling Pathway Initiators.International journal of molecular sciences · 2022Article
- Long-read assembly of a Great Dane genome highlights the contribution of GC-rich sequence and mobile elements to canine genomes.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Expression of DLX6 Gene in Mandibular Deficiency (Retrognathic Mandible): A Randomized Clinical and Genetic Study.Cureus · 2021Article
- Phenotypes, Developmental Basis, and Genetics of Pierre Robin Complex.Journal of developmental biology · 2020Review
- Prenatal diagnosis of foetal hydrocephalus and suspected X-linked recessive inheritance of cleft lip in a Chihuahua.The Journal of veterinary medical science · 2020Article
- Incidence patterns of orofacial clefts in purebred dogs.PloS one · 2019Article
- Computed tomographic evaluation of cleft palate in one-day-old puppies.BMC veterinary research · 2018Article
- 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
- A splice site variant in INPP5E causes diffuse cystic renal dysplasia and hepatic fibrosis in dogs.PloS one · 2018Article
- Zebrafish models of orofacial clefts.Developmental dynamics : an official publication of the American Association of Anatomists · 2017Review
- A Novel Heterozygous Intragenic Sequence Variant inMolecular syndromology · 2017Article
- Congenital Malformations in River Buffalo (Bubalus bubalis).Animals : an open access journal from MDPI · 2017Review
- 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
- An intronic LINE-1 insertion in MERTK is strongly associated with retinopathy in Swedish Vallhund dogs.PloS one · 2017Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Cleft palate (CP) is one of the most commonly occurring craniofacial birth defects in humans. In order to study cleft palate in a naturally occurring model system, we utilized the Nova Scotia Duck Tolling Retriever (NSDTR) dog breed. Micro-computed tomography analysis of CP NSDTR craniofacial structures revealed that these dogs exhibit defects similar to those observed in a recognizable subgroup of humans with CP: Pierre Robin Sequence (PRS). We refer to this phenotype in NSDTRs as CP1. Individuals with PRS have a triad of birth defects: shortened mandible, posteriorly placed tongue, and cleft palate. A genome-wide association study in 14 CP NSDTRs and 72 unaffected NSDTRs identified a significantly associated region on canine chromosome 14 (24.2 Mb-29.3 Mb; p(raw )= 4.64 × 10(-15)). Sequencing of two regional candidate homeobox genes in NSDTRs, distal-less homeobox 5 (DLX5) and distal-less homeobox 6 (DLX6), identified a 2.1 kb LINE-1 insertion within DLX6 in CP1 NSDTRs. The LINE-1 insertion is predicted to insert a premature stop codon within the homeodomain of DLX6. This prompted the sequencing of DLX5 and DLX6 in a human cohort with CP, where a missense mutation within the highly conserved DLX5 homeobox of a patient with PRS was identified. This suggests the involvement of DLX5 in the development of PRS. These results demonstrate the power of the canine animal model as a genetically tractable approach to understanding naturally occurring craniofacial birth defects in humans.
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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.