Multiocular defect in the Old English Sheepdog: A canine form of Stickler syndrome type II associated with a missense variant in the collagen-type gene COL11A1.

Multiocular defect has been described in different canine breeds, including the Old English Sheepdog. Affected dogs typically present with multiple and various ocular abnormalities. We carried out whole genome sequencing on an Old English Sheepdog that had been diagnosed with hereditary cataracts at the age of five and then referred to a board-certified veterinary ophthalmologist due to owner-reported visual deterioration.

Women's Attitudes Toward Intimate Partner Violence in Low- and Middle-Income Countries of Southern Asia.

Purpose: The present study identified the vulnerable IPV cohorts of South Asian women, and the prevalence of and predictors of the women's IPV acceptance.

Design: Cross-sectional survey - the United Nations Children's Fund multiple index cluster survey.

Setting: Many South Asian women are accepting of IPV.

A TNR Frameshift Variant in Weimaraner Dogs with an Exercise-Induced Paroxysmal Movement Disorder.

Background: Some paroxysmal movement disorders remain without an identified genetic cause.

Objectives: The aim was to identify the causal genetic variant for a paroxysmal dystonia-ataxia syndrome in Weimaraner dogs.

Methods: Clinical and diagnostic investigations were performed.

Relationship between change in social evaluation learning and mood in early antidepressant treatment: A prospective cohort study in primary care.

Background: Antidepressants are proposed to work by increasing sensitivity to positive versus negative information. Increasing positive affective learning within social contexts may help remediate negative self-schema. We investigated the association between change in biased learning of social evaluations about the self and others, and mood during early antidepressant treatment.

A LINE-1 insertion situated in the promoter of IMPG2 is associated with autosomal recessive progressive retinal atrophy in Lhasa Apso dogs.

Background: Canine progressive retinal atrophies are a group of hereditary retinal degenerations in dogs characterised by depletion of photoreceptor cells in the retina, which ultimately leads to blindness. PRA in the Lhasa Apso (LA) dog has not previously been clinically characterised or described in the literature, but owners in the UK are advised to have their dog examined through the British Veterinary Association/ Kennel Club/ International Sheep Dog Society (BVA/KC/ISDS) eye scheme annually, and similar schemes that are in operation in other countries. After the exclusion of 25 previously reported canine retinal mutations in LA PRA-affected dogs, we sought to identify the genetic cause of PRA in this breed.

NME5 frameshift variant in Alaskan Malamutes with primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a hereditary defect of motile cilia in humans and several domestic animal species. Typical clinical findings are chronic recurrent infections of the respiratory tract and fertility problems. We analyzed an Alaskan Malamute family, in which two out of six puppies were affected by PCD.

Clinical, histopathological and genetic characterisation of oculoskeletal dysplasia in the Northern Inuit Dog.

Seven Northern Inuit Dogs (NID) were diagnosed by pedigree analysis with an autosomal recessive inherited oculoskeletal dysplasia (OSD). Short-limbed dwarfism, angular limb deformities and a variable combination of macroglobus, cataracts, lens coloboma, microphakia and vitreopathy were present in all seven dogs, while retinal detachment was diagnosed in five dogs. Autosomal recessive OSD caused by COL9A3 and COL9A2 mutations have previously been identified in the Labrador Retriever (dwarfism with retinal dysplasia 1-drd1) and Samoyed dog (dwarfism with retinal dysplasia 2-drd2) respectively; both of those mutations were excluded in all affected NID.

Evaluation of ADAMTS17 in Chinese Shar-Pei with primary open-angle glaucoma, primary lens luxation, or both.

OBJECTIVE To evaluate the coding regions of ADAMTS17 for potential mutations in Chinese Shar-Pei with a diagnosis of primary open-angle glaucoma (POAG), primary lens luxation (PLL), or both. ANIMALS 63 Shar-Pei and 96 dogs of other breeds. PROCEDURES ADAMTS17 exon resequencing was performed on buccal mucosal DNA from 10 Shar-Pei with a diagnosis of POAG, PLL, or both (affected dogs).

An intronic LINE-1 insertion in MERTK is strongly associated with retinopathy in Swedish Vallhund dogs.

The domestic dog segregates a significant number of inherited progressive retinal diseases, several of which mirror human retinal diseases and which are collectively termed progressive retinal atrophy (PRA). In 2014, a novel form of PRA was reported in the Swedish Vallhund breed, and the disease was mapped to canine chromosome 17. The causal mutation was not identified, but expression analyses of the retinas of affected Vallhunds demonstrated a 6-fold increased expression of the MERTK gene compared to unaffected dogs.

A Carbohydrate Sulfotransferase-6 (CHST6) gene mutation is associated with Macular Corneal Dystrophy in Labrador Retrievers.

Purpose: To locate and identify variants associated with macular corneal dystrophy (MCD) in Labrador Retriever (LR) dogs, in the candidate gene carbohydrate sulfotransferase-6 (CHST6).

Methods: The single coding exon of canine CHST6 was sequenced in one affected LR with MCD and one control LR clinically clear of ocular disease. A further 71 control LR with unknown clinical status were sequenced for the putative causal variant in CHST6.

An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed.

Sensory neuropathy in the Border Collie is a severe neurological disorder caused by the degeneration of sensory and, to a lesser extent, motor nerve cells with clinical signs starting between 2 and 7 months of age. Using a genome-wide association study approach with three cases and 170 breed matched controls, a suggestive locus for sensory neuropathy was identified that was followed up using a genome sequencing approach. An inversion disrupting the candidate gene FAM134B was identified.

Correction: Two Independent Mutations in ADAMTS17 Are Associated with Primary Open Angle Glaucoma in the Basset Hound and Basset Fauve de Bretagne Breeds of Dog.

[This corrects the article DOI: 10.1371/journal.pone.

A Novel Genome-Wide Association Study Approach Using Genotyping by Exome Sequencing Leads to the Identification of a Primary Open Angle Glaucoma Associated Inversion Disrupting ADAMTS17.

Closed breeding populations in the dog in conjunction with advances in gene mapping and sequencing techniques facilitate mapping of autosomal recessive diseases and identification of novel disease-causing variants, often using unorthodox experimental designs. In our investigation we demonstrate successful mapping of the locus for primary open angle glaucoma in the Petit Basset Griffon Vendéen dog breed with 12 cases and 12 controls, using a novel genotyping by exome sequencing approach. The resulting genome-wide association signal was followed up by genome sequencing of an individual case, leading to the identification of an inversion with a breakpoint disrupting the ADAMTS17 gene.

Two Independent Mutations in ADAMTS17 Are Associated with Primary Open Angle Glaucoma in the Basset Hound and Basset Fauve de Bretagne Breeds of Dog.

Purpose: Mutations in ADAMTS10 (CFA20) have previously been associated with primary open angle glaucoma (POAG) in the Beagle and Norwegian Elkhound. The closely related gene, ADAMTS17, has also been associated with several different ocular phenotypes in multiple breeds of dog, including primary lens luxation and POAG. We investigated ADAMTS17 as a candidate gene for POAG in the Basset Hound and Basset Fauve de Bretagne dog breeds.

A novel locus on canine chromosome 13 is associated with cataract in the Australian Shepherd breed of domestic dog.

Hereditary cataract is a common ocular disorder in the purebred dog population and is a leading cause of visual impairment and blindness in dogs. Despite this, little is known to date about the genetics underlying this condition. We have used a genome-wide association study and targeted resequencing approach to identify a novel locus for cataracts in the Australian Shepherd breed of dog, using dogs that are clear of an HSF4 mutation, previously identified as the major susceptibility locus in this breed.

Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in Cavalier King Charles spaniel dogs. Part II: candidate gene study.

Purpose: To identify causative mutation(s) for congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID) in Cavalier King Charles spaniel (CKCS) dogs using a candidate gene approach.

Methods: DNA samples from 21 cases/parents were collected. Canine candidate genes (CCGs) for similar inherited human diseases were chosen.

ADAMTS17 mutation associated with primary lens luxation is widespread among breeds.

Primary lens luxation (PLL) is a well-recognized, painful and potentially blinding inherited ocular condition in dogs. We screened PLL-affected dogs of 30 different breeds, to identify those which carried a previously described c.1473+1 G>A mutation in ADAMTS17 that is associated with PLL in Miniature Bull terriers, Lancashire Heelers, and Jack Russell terriers.

An ADAMTS17 splice donor site mutation in dogs with primary lens luxation.

Purpose: To identify the genetic cause of isolated canine ectopia lentis, a well-characterized veterinary disease commonly referred to as primary lens luxation (PLL) and to compare the canine disease with a newly described human Weill-Marchesani syndrome (WMS)-like disease of similar genetic etiology.

Methods: Genomewide association analysis and fine mapping by homozygosity were used to identify the chromosomal segment harboring the PLL locus. The resequencing of a regional candidate gene was used to discover a mutation in a splice donor site predicted to cause exon skipping.

Mutation in HSF4 is associated with hereditary cataract in the Australian Shepherd.

Cataracts are a leading cause of blindness in dogs with approximately 100 breeds affected by primary hereditary forms. Despite the large number of breeds affected with hereditary cataracts (HC) little is known about the genetics of the condition, and to date only a single gene, HSF4, has been implicated in the development of the disease in dogs. We previously identified a recessively inherited 1-bp insertion in the transcription factor gene HSF4 resulting in the loss of the open reading frame in Boston terriers and Staffordshire bull terriers.

Mutation in HSF4 associated with early but not late-onset hereditary cataract in the Boston Terrier.

Primary hereditary cataract (HC) is one of the most common disorders in purebred dogs and is a leading cause of blindness. Boston Terriers suffer from 2 distinct forms of HC which occur at different ages and which are different in their appearance and progression. Early-onset hereditary cataract (EHC) affects dogs within the first few months of life, is always progressive and bilateral, and results in total blindness, whereas late-onset hereditary cataract (LHC) in general affects dogs over the age of 3 and is more variable in its clinical phenotype, age of onset, progression, and the degree to which vision is impaired.

Mapping the mutation causing lens luxation in several terrier breeds.

Primary lens luxation (PLL), a painful and blinding inherited condition, is common in several breeds of terrier. Here we have examined the Veterinary Medical Database of patient encounters and Canine Eye Registration Foundation (CERF) cases records for the last 10 years and found the diagnosis recorded in 85 breeds. We have performed association analysis using a genome-wide microsatellite screen to map mutations underlying the condition in miniature bull terriers and Lancashire heelers.

L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model.

l-2-hydroxyglutaric aciduria (l-2-HGA) is a neurometabolic disorder that produces a variety of clinical neurological deficits, including psychomotor retardation, seizures and ataxia. The biochemical hallmark of l-2-HGA is the accumulation of l-2-hydroxyglutaric acid (l-2-HG) in cerebrospinal fluid, plasma and urine. Mutations within the gene L2HGDH (Entrez Gene ID 79944) on chromosome 14q22 encoding L-2-hydroxyglutaric acid dehydrogenase have recently been shown to cause l-2-HGA in humans.

Identification of mutations in HSF4 in dogs of three different breeds with hereditary cataracts.

Cataracts are a leading cause of blindness in both dogs and humans. Mutations in several genes have been associated with inherited forms of human cataract, but no mutations have been identified as the cause of any form of canine inherited cataract. We have used a candidate gene approach to investigate 20 genes, known to be associated with cataract in humans, for their potential association with the development of hereditary cataract (HC) in dogs.

Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis.

Cone-rod dystrophy 1 (cord1) is a recessive condition that occurs naturally in miniature longhaired dachshunds (MLHDs). We mapped the cord1 locus to a region of canine chromosome CFA15 that is syntenic with a region of human chromosome 14 (HSA14q11.2) containing the retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) gene.

Single linkage group per chromosome genetic linkage map for the horse, based on two three-generation, full-sibling, crossbred horse reference families.

A genetic linkage map of the horse consisting of 742 markers, which comprises a single linkage group for each of the autosomes and the X chromosome, is presented. The map has been generated from two three-generation full-sibling reference families, sired by the same stallion, in which there are 61 individuals in the F2 generation. Each linkage group has been assigned to a chromosome and oriented with reference to markers mapped by fluorescence in situ hybridization.