Cloning and characterization of WDR17, a novel WD repeat-containing gene on chromosome 4q34

Stöhr, Heidi; Mohr, Nicole; Fröhlich, Susanne; Mehdi, S. Qasim; Bhattacharya, Siladitya; Weber, Bernhard H. F.

doi:10.1016/s0167-4781(02)00499-2

Cited by 13 publications

(11 citation statements)

References 22 publications

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“…In a large sequencing study of medulloblastoma, a single missense mutation in C16orf11 was identified in one sample (Parsons et al, 2008). Lastly, WDR17 is expressed in retina and testis and is a candidate gene for autosomal recessive retinitis pigmentosa (Stohr et al, 2002; Roni et al, 2007; Geisert et al, 2009). In the COSMIC database, missense and synonymous mutations in WDR17 have been occasionally reported in medulloblastoma, ovary carcinoma and malignant melanoma (Wellcome Trust Sanger Institute COSMIC database, accessed September 15, 2011).…”

Section: Discussionmentioning

confidence: 99%

Mitotic recombination of chromosome arm 17q as a cause of loss of heterozygosity of NF1 in neurofibromatosis type 1‐associated glomus tumors

Stewart

Pemov

Loo

et al. 2012

Genes Chromosomes & Cancer

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Neurofibromatosis type 1 (NF1) is a common, autosomal dominant, tumor-predisposition syndrome that arises secondary to mutations in NF1. Glomus tumors are painful benign tumors that originate from the glomus body in the fingers and toes due to biallelic inactivation of NF1. We karyotyped cultures from four previously reported and one new glomus tumor and hybridized tumor (and matching germline) DNA on Illumina HumanOmni1-Quad SNP arrays (~1 × 106 SNPs). Two tumors displayed evidence of copy-neutral loss of heterozygosity of chromosome arm 17q not observed in the germline sample, consistent with a mitotic recombination event. One of these two tumors, NF1-G12, featured extreme polyploidy (near-tetraploidy, near-hexaploidy, or near-septaploidy) across all chromosomes. In the remaining four tumors, there were few cytogenetic abnormalities observed, and copy-number analysis was consistent with diploidy in all chromosomes. This is the first study of glomus tumors cytogenetics, to our knowledge, and the first to report biallelic inactivation of NF1 secondary to mitotic recombination of chromosome arm 17q in multiple NF1-associated glomus tumors. We have observed mitotic recombination in 22% of molecularly-characterized NF1-associated glomus tumors, suggesting that it is a not uncommon mechanism in the reduction to homozygosity of the NF1 germline mutation in these tumors. In tumor NF1-G12, we hypothesize that mitotic recombination also “unmasked” (reduced to homozygosity) a hypomorphic germline allele in a gene on chromosome arm 17q associated with chromosomal instability, resulting in the extreme polyploidy.

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Section: Discussionmentioning

confidence: 99%

Mitotic recombination of chromosome arm 17q as a cause of loss of heterozygosity of NF1 in neurofibromatosis type 1‐associated glomus tumors

Stewart

Pemov

Loo

et al. 2012

Genes Chromosomes & Cancer

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“…The human total RNA master panel was purchased from BD Biosciences Clontech. RT-PCRs were performed with primer pair A126F2 (5Ј-CATCATTCCTCATCCCA TC-3Ј)/A126R (5Ј-GAGGCAAAGTTC ATCAGG-3Ј) for human TMEM16B and Tmem16b-F1 (5Ј-CACAACGGGACACTACATGG-3Ј)/Tmem16b-R1 (5Ј-CTTAAGCC AGTTCCCAGCA G-3Ј) for mouse Tmem16b as previously described (Stöhr et al, 2002). Primers specific for constitutively expressed housekeeping genes glyceraldehyde-3-phosphate dehydrogenase (G3PDH ) and ␤-glucuronidase (Gusb) have been described previously (Stöhr et al, 2000(Stöhr et al, , 2002.…”

Section: Methodsmentioning

confidence: 99%

TMEM16B, A Novel Protein with Calcium-Dependent Chloride Channel Activity, Associates with a Presynaptic Protein Complex in Photoreceptor Terminals

Stöhr¹,

Heisig²,

Benz³

et al. 2009

J. Neurosci.

194

186

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Photoreceptor ribbon synapses release glutamate in response to graded changes in membrane potential evoked by vast, logarithmically scalable light intensities. Neurotransmitter release is modulated by intracellular calcium levels. Large Ca 2ϩ -dependent chloride currents are important regulators of synaptic transmission from photoreceptors to second-order neurons; the molecular basis underlying these currents is unclear. We cloned human and mouse TMEM16B, a member of the TMEM16 family of transmembrane proteins, and show that it is abundantly present in the photoreceptor synaptic terminals in mouse retina. TMEM16B colocalizes with adaptor proteins PSD95, VELI3, and MPP4 at the ribbon synapses and contains a consensus PDZ class I binding motif capable of interacting with PDZ domains of PSD95. Furthermore, TMEM16B is lost from photoreceptor membranes of MPP4-deficient mice. This suggests that TMEM16B is a novel component of a presynaptic protein complex recruited to specialized plasma membrane domains of photoreceptors. TMEM16B confers Ca 2ϩ -dependent chloride currents when overexpressed in mammalian cells as measured by halide sensitive fluorescent protein assays and whole-cell patch-clamp recordings. The compartmentalized localization and the electrophysiological properties suggest TMEM16B to be a strong candidate for the long sought-after Ca 2ϩ -dependent chloride channel in the photoreceptor synapse.

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“…At least two genes within this interval ( WDR17 , GPM6A ), and one gene near the interval ( CCN3 ), were previously examined by sequencing and were excluded as candidates [74]. In our data, only one gene, KIAA1712 , was both located within the mapped interval and selectively expressed in our retinal samples.…”

Section: Resultsmentioning

confidence: 84%

Untitled

Diehn

Marmor

et al. 2005

Genome Biol

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Profiling human eye compartments

DNA microarrays (representing approximately 30,000 human genes) were used to analyze gene expression in six different human eye compartments, revealing candidate genes for diseases affecting the cornea, lens and retina.

Abstract Background: The human eye is composed of multiple compartments, diverse in form, function, and embryologic origin, that work in concert to provide us with our sense of sight. We set out to systematically characterize the global gene expression patterns that specify the distinctive characteristics of the various eye compartments.

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Cloning and characterization of WDR17, a novel WD repeat-containing gene on chromosome 4q34

Cited by 13 publications

References 22 publications

Mitotic recombination of chromosome arm 17q as a cause of loss of heterozygosity of NF1 in neurofibromatosis type 1‐associated glomus tumors

Mitotic recombination of chromosome arm 17q as a cause of loss of heterozygosity of NF1 in neurofibromatosis type 1‐associated glomus tumors

TMEM16B, A Novel Protein with Calcium-Dependent Chloride Channel Activity, Associates with a Presynaptic Protein Complex in Photoreceptor Terminals

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