Genetic mapping of a cone and rod dysfunction (Aland Island eye disease) to the proximal short arm of the human X chromosome.

Glass, I. A.; Good, Peter; Coleman, Michael P.; Fullwood, P; Giles, M.; Lindsay, Susan; Németh, Andrea H.; Davies, Kay E.; Willshaw, H A; Fielder, A. H. L.

doi:10.1136/jmg.30.12.1044

Cited by 32 publications

(12 citation statements)

References 19 publications

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“…A total of 41 of the validated candidate genes have human orthologs, 7 of which have previously been associated with vision disorders. cac, which encodes a calcium channel, has seven human orthologs that also encode calcium channel subunits, of which CACNA1F has been associated with congenital night blindness (CSNB2A) (78), Aland Island eye disease (AIED) (79,80), and X-linked conerod dystrophy (CORDX3) (81). fz encodes a seven-transmembrane helix containing protein necessary for binding Wnt ligands in the noncanonical Wnt signaling pathway (82) and has 10 human orthologs encoding frizzled class receptors, of which FZD4 is associated with exudative vitreoretinopathy (83).…”

Section: Discussionmentioning

confidence: 99%

Genetic architecture of natural variation in visual senescence in Drosophila

Carbone

Yamamoto

Huang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Senescence, i.e., functional decline with age, is a major determinant of health span in a rapidly aging population, but the genetic basis of interindividual variation in senescence remains largely unknown. Visual decline and age-related eye disorders are common manifestations of senescence, but disentangling age-dependent visual decline in human populations is challenging due to inability to control genetic background and variation in histories of environmental exposures. We assessed the genetic basis of natural variation in visual senescence by measuring age-dependent decline in phototaxis using Drosophila melanogaster as a genetic model system. We quantified phototaxis at 1, 2, and 4 wk of age in the sequenced, inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and found an average decline in phototaxis with age. We observed significant genetic variation for phototaxis at each age and significant genetic variation in senescence of phototaxis that is only partly correlated with phototaxis. Genome-wide association analyses in the DGRP and a DGRP-derived outbred, advanced intercross population identified candidate genes and genetic networks associated with eye and nervous system development and function, including seven genes with human orthologs previously associated with eye diseases. Ninety percent of candidate genes were functionally validated with targeted RNAi-mediated suppression of gene expression. Absence of candidate genes previously implicated with longevity indicates physiological systems may undergo senescence independent of organismal life span. Furthermore, we show that genes that shape early developmental processes also contribute to senescence, demonstrating that senescence is part of a genetic continuum that acts throughout the life span.aging | behavioral genetics | DGRP GWA analysis | phototaxis | xQTL mapping

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Section: Discussionmentioning

confidence: 99%

Genetic architecture of natural variation in visual senescence in Drosophila

Carbone

Yamamoto

Huang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…14,19 Several ophthalmological findings in this family such as negative scotopic and abnormal photopic waveforms of the electroretinogram, and the defective dark adaptometry 20 suggested allelic heterogeneity to incomplete XLCSNB. 14 Analysis of all 48 exons of the CACNA1F gene by complete DNA sequencing revealed no aberration in an affected male.…”

Section: Is6mentioning

confidence: 99%

Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina

Wutz¹,

Sauer

Zrenner³

et al. 2002

Eur J Hum Genet

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X-linked CSNB patients may exhibit myopia, nystagmus, strabismus and ERG abnormalities of the Schubert-Bornschein type. We recently identified the retina-specific L-type calcium channel a1 subunit gene CACNA1F localised to the Xp11.23 region, which is mutated in families showing the incomplete type (CSNB2). Here, we report comprehensive mutation analyses in the 48 CACNA1F exons in 36 families, most of them from Germany. All families were initially diagnosed as having the incomplete type of CSNB, except for two which have been designated as Å land Island eye disease (Å IED)-like. Out of 33 families, a total of 30 different mutations were identified, of which 24 appear to be unique for the German population. The mutations, 20 of which are published here for the first time, were found to be equally distributed over the entire gene sequence. No mutation could be found in a classic Å IED family previously shown to map to the CSNB2 interval. Cacna1f expression in photoreceptor-negative mice strains indicate that the gene is expressed in the outer nuclear, the inner nuclear, and the ganglion cell layer. Such a distribution points to the central role of calcium regulation in the interaction of retinal cells that mediate signal transmission.

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“…All these cDNAs were excluded as candidate genes for RP2 in a single family but remain candidate genes for CSNB1 (Bech-Hansen and Pearce 1993) and the Aland Island eye disease (Glass et al 1993). The EPB gene (Harmer et al 1995) lies adjacent to MG61, and the RBM gene (Derry et al 1995a) next to MG81, and both are, because of their functional role, not expected to be associated with eye diseases.…”

Section: Candidate Genes In the Gene-rich Intervalmentioning

confidence: 99%

“…] Multiple genes and disease loci have been mapped to the Xp11.23-22 region. A gene mutated in Wiskott-Aldrich syndrome (WAS) patients has been identified recently by positional cloning (Derry et al 1994), whereas the genes for a number of disease loci including a type of Xlinked congenital stationary night blindness (CSNB) (Bech-Hansen and Pearce 1993), retinitis pigmentosa (xlRP) (Meitinger et al 1989;Ott et al 1990) and Aland Island eye disease (Glass et al 1993) remain to be isolated. In addition, at least four X-linked mental retardation loci (MRX1, MRX8, MRX12, MRX26; Lubs et al 1996) and X-linked infantile spinal muscular atrophy (Kobayashi et al 1995) have been linked to this region.…”

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confidence: 99%

Long-range map of a 3.5-Mb region in Xp11.23-22 with a sequence-ready map from a 1.1-Mb gene-rich interval.

Schindelhauer

Hellebrand²,

Grimm

et al. 1996

Genome Res.

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Most of the yeast artificial chromosomes (YACs} isolated from the Xp11.23-22 region have shown instability and chimerism and are not a reliable resource for determining physical distances. We therefore constructed a long-range pulsed-field gel electrophoresis map that encompasses -3.5 Mb of genomic DNA between the loci TIMP and DXSI46 including a CpG-rich region around the WASP and TFE-3 gene loci. A combined YAC-cosmid contig was constructed along the genomic map and was used for fine-mapping of 15 polymorphic microsatellites and 30 expressed sequence tags (ESTs} or sequence transcribed sites {STSs}, revealing the following order: teI~SYN-TIMPHDXS426-ELKI~ZNF(CAJn

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Genetic mapping of a cone and rod dysfunction (Aland Island eye disease) to the proximal short arm of the human X chromosome.

Abstract: A five generation family with an X linked ocular disorder has been investigated. The major clinical features were reduced visual acuity, nystagmus, and myopia.

Cited by 32 publications

References 19 publications

Genetic architecture of natural variation in visual senescence in Drosophila

Genetic architecture of natural variation in visual senescence in Drosophila

Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina

Long-range map of a 3.5-Mb region in Xp11.23-22 with a sequence-ready map from a 1.1-Mb gene-rich interval.

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