A study of candidate genes for day blindness in the standard wire haired dachshund

<p>Abstract</p> <p>Background</p> <p>A genetic study was performed to identify candidate genes associated with day blindness in the standard wire haired dachshund. Based on a literature review of diseases in dogs and human with phenotypes similar to day blindness, ten genes were selected and evaluated as potential candidate genes associated with day blindness in the breed.</p> <p>Results</p> <p>Three of the genes, <it>CNGB3</it>, <it>CNGA3 </it>and <it>GNAT2</it>, involved in cone degeneration and seven genes and loci, <it>ABCA4</it>, <it>RDH5</it>, <it>CORD8</it>, <it>CORD9</it>, <it>RPGRIP1</it>, <it>GUCY2D </it>and <it>CRX</it>, reported to be involved in cone-rod dystrophies were studied. Polymorphic markers at each of the candidate loci were studied in a family with 36 informative offspring. The study revealed a high frequency of recombinations between the candidate marker alleles and the disease.</p> <p>Conclusion</p> <p>Since all of the markers were at the exact position of the candidate loci, and several recombinations were detected for each of the loci, all ten genes were excluded as causal for this canine, early onset cone-rod dystrophy. The described markers may, however, be useful to screen other canine resource families segregating eye diseases for association to the ten genes.</p

ZEN-definisjonen – En veileder for ZEN-pilotområder. Versjon 3.0. norsk

Denne tredje utgaven av ZEN-definisjonsveilederen bygger på versjon 1.0 og 2.0 av ZEN-definisjonsveilederne og ZEN-definisjonsrapporter. Denne rapporten presenterer ZEN KPI-verktøyet i mer detalj og gir mer informasjon om ZEN KPI-referanse-, grense-, og målverdier. En stor endring inkluderer å løfte prosess-nøkkelindikatorer ut av stedskvaliteterkategorien og å tilpasse dem til en prosessveileder for design og planlegging av ZEN-områder. Detaljer har blitt supplert for hver nøkkelindikator for å forklare i hvilken grad de bidrar til målsetningen av ZEN samt gir eksempler på beste praksis. Noen nye nøkkelindikatorer har blitt lagt til. Navnet på kategorien stedskvaliteter har blitt endret til byform og arealbruk.This third version of the ZEN definition guideline report builds upon version 1.0 and 2.0 of the ZEN definition guideline reports and series of ZEN definition reports. This report gives further details on the ZEN KPI tool and on ZEN KPI reference, limit, and target values. A major change involves lifting the process KPIs out of spatial qualities and incorporating them into a process guideline for designing ZENs. Details have been added to each KPI to explain to what degree it contributes to the main goal of ZEN, and examples of best practice are given. Additional power KPIs have been added. The spatial qualities category has been renamed to urban form and land use.publishedVersio

Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping

Peer reviewe

Functional and structural changes in the retina of wire-haired dachshunds with early-onset cone-rod dystrophy

PURPOSE. To describe and classify the morphologic changes in a naturally occurring dog model of early-onset cone-rod dystrophy (CRD) and to correlate these with earlier described clinical characteristics of the disease in dogs. METHODS. Purpose-bred Standard Wire-Haired Dachshunds (SWHDs) derived from a large pedigree of dogs with earlyonset CRD were euthanatized at defined ages to characterize morphologic changes in the disease process. Specimens were examined by light microscopy, including morphometric studies, electron microscopy, and immunohistochemistry. Peanut agglutinin (PNA), protein kinase C (PKC), synaptophysin (Syn), rhodopsin (Rho)-63, glial fibrillary acidic protein (GFAP), and short-wavelength cone opsin (OS) were used for immunohistochemical characterization. RESULTS. The photopic cone-system-derived ERG amplitudes were already significantly reduced or nonrecordable in CRD-affected dogs at 5 weeks, the earliest age studied. The outer retina was morphologically most severely affected initially, with a subsequent degeneration of the inner retina. Cone degeneration was more pronounced than rod degeneration in young CRD-affected dogs. There was a marked phenotypic variation based on morphologic findings in the affected dogs. At the earliest time point studied (5-8 weeks) cone photoreceptor and glial cell abnormalities were observed, in accordance with earlier studies based on electrophysiological and clinical findings in which day blindness and abnormal cone ERGs were observed in young affected SWHD puppies. Preliminary genetic studies have indicated an autosomal recessive mode of inheritance for the defect. CONCLUSIONS. Through functional and structural characterization, early-onset cone abnormalities were found, consistent with a cone dysplasia at an age when rod structure was normal. Further studies are in progress to identify the gene(s) involved in this retinal disease process. The presently described natural animal model of primary cone dysplasia followed by rod degeneration may provide further insight into the human counterpart. Further studies are needed to ascertain an autosomal recessive mode of inheritance for CRD in the SWHD

A deletion in nephronophthisis 4 (NPHP4) is associated with recessive cone-rod dystrophy in standard wire-haired dachshund

Cone-rod dystrophy is a retinal degenerative disorder occurring naturally in man and dog. Here we identify a novel gene for early-onset cone-rod dystrophy in the wire-haired dachshund. For the first time, we use genome-wide association-based Sibling Transmission Disequilibrium Test (sibTDT) analysis of only 13 discordant sib-pairs to identify a single significantly associated 6.5-Mb region (PrawTDT = 4.8 × 10−5, PgenomeTDT = 6 × 10−4) on canine chromosome 5, containing more than 70 genes. Segregation studies using microsatellites in the candidate region including additional meiosis supported the sibTDT analysis but could not further reduce the area. Candidate gene resequencing identified a 180-bp deletion in exon/intron 5 of NPHP4 (nephronophthisis 4, also known as nephroretinin). RT-PCR analysis of NPHP4 in cases and controls showed exon skipping of exon 5, resulting in a truncated protein that retains the binding domain interacting with nephronophthisis 1 (also known as nephrocystin-1) in the kidney but lacks the domain interacting with RPGRIP1 in retina. We suggest that this deletion in the canine NPHP4 gene is the cause of cone-rod dystrophy in the standard wire-haired dachshund. In humans, mutations in NPHP4 have been associated with simultaneous eye and kidney disease. Here we describe the first naturally occurring mutation in NPHP4 without additional kidney disease. Further studies will permit elucidation of the complex molecular mechanism of this retinopathy and the development of potential therapies

Zero Emission Neighbourhoods in Smart Cities

This document outlines the definition, key performance indicators (KPI) and assessment criteria for the Research Centre on Zero Emission Neighbourhoods in Smart Cities (ZEN research centre). This fourth version of the ZEN definition builds upon previous versions of the ZEN definition report and the third version of the ZEN definition guideline report. This report gives details on the ZEN definition framework. A major change involves lifting the process KPIs out of spatial qualities and incorporating them into a process guideline for designing ZENs. Additional power KPIs have been added. The spatial qualities category has been renamed to urban form and land use, and additional KPIs have been added. This report has been shortened to give a synopsis of the ZEN definition and important definitions relating to the ZEN definition framework. Further details on ZEN KPIs can be found in the ZEN definition guideline report version 3.0. Over 100 people involved in the ZEN research centre have contributed to this document.publishedVersio

Nullutslippsområde i smarte byerDefinisjon, nøkkelindikatorer og vurderingskriterier: Versjon 4.0

Denne rapporten beskriver definisjoner, nøkkelindikatorer og vurderingskriterier som benyttes i Forskningssenter for nullutslippsområder i smarte byer (ZEN-senteret). Versjon 4.0 bygger på tidligere versjoner av ZEN-definisjonsrapport og tredje versjon av rapporten ZEN definisjonsveileder (1). Versjon 4.0 gir detaljer om ZEN definisjonsrammeverk. En stor endring involverer å løfte prosess-KPI-er ut av kategorien "stedskvaliteter" og å inkludere dem i en prosessveileder for å designe ZEN. Flere effekt-KPI-er er lagt til. Kategorien "stedskvaliteter" heter nå "byform og arealbruk (BYF)" og flere KPI-er er lagt til. Denne rapporten er kortere enn tidligere versjoner og gir oversikt over ZEN-definisjonen og viktige definisjoner relatert til ZEN definisjonsrammeverk. Flere detaljer om ZEN KPI finnes i rapporten ZEN definisjonsveileder versjon 3.0. Til sammen har over 100 eksperter fra ZEN-senteret bidratt til dette dokumentet.publishedVersio

Nullutslippsnabolag i smarte byer: Definisjon, vurderingskriterier og nøkkelindikatorer: Versjon 3.0

Denne rapporten beskriver definisjonen, nøkkelindikatorer og vurderingskriterier som benyttes i forskningssenteret for nullutslippsområde i smarte byer (ZEN senteret). Denne tredje utgaven av ZEN-definisjonen bygger på tidligere versjoner av ZEN-definisjonen. Klimagassutslipp (KGU), energi (ENE) og effekt (EFF) kategoriene har blitt videre utviklet og raffinert gjennom empirisk forskning og iterativ testing i ZEN pilotområdene. Tabell 2: ZEN-vurderingskriterier og nøkkelindikatorer (KPI) er revidert. Justeringer for kategoriene mobilitet (MOB), økonomi (ØKO), stedskvaliteter (KVA) og innovasjon (INN) er gjennomført. Innovasjon inneholder ikke lenger ZEN vurderingskriterier eller nøkkel-indikatorer, men er fortsatt en viktig prosess som skal forskes videre på i de neste utgavene av ZEN definisjonsrapport. Rapporten er tilgjengelig i en engelsk versjon (EN) og en norsk versjon (NO). Til sammen har over 100 eksperter fra ZEN senteret bidratt til dette dokumentet