A YAC Contig Spanning the Dominant Retinitis Pigmentosa Locus (RP9) on Chromosome 7p

doi:10.1006/geno.1995.1165

Genomics

Volume 28, Issue 3, 10 August 1995, Pages 383-388

https://doi.org/10.1006/geno.1995.1165 Get rights and content

Abstract

The dominant retinitis pigmentosa locus RP9 has previously been localized to 7p13-p15, in the interval D7S526-D7S484. We now report refinement of the locus to the interval D7S795-D7S484 and a YAC contig of approximately 4.8 Mb spanning this region and extending both distally and proximally from it. The contig was constructed by STS content mapping and physically orders 29 STSs in 28 YAC clones. The order of polymorphic markers in the contig is consistent with a genetic map that has been assembled using haplotype data from the CEPH pedigrees. This contig will provide a primary resource for the construction of a transcriptional map of this region and for the identification of the defective gene causing this form of adRP.

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Cited by (15)

Defective trafficking of rhodopsin and its role in retinal degenerations
2012, International Review of Cell and Molecular Biology
Citation Excerpt :
Other genes resulting in ADRP and ARRP include Rp1, Nrl, Crx, Best1, and Impdh1 (Bessant et al., 1999b; Blanton et al., 1991; Bowne et al., 2002; Davidson et al., 2009; Tzekov et al., 2001). Genes thus far known to be unique to ADRP code for precursor mRNA-processing factors 31, 8, and 3 (PRPF31, PRPF8, PRPF3) and Pim-1-associated protein (RP9), all of which are involved in RNA splicing, topoisomerase I-binding RS protein (TOPORS), a RING domain-containing E3 ubiquitin ligase, the structural proteins peripherin (RDS) and fascin (FSCN2), an activator of T-cell-mediated immunity semaphorin B (SEMA4A) which also serves to guide axons in the developing nervous system, the pH regulating carbonic anhydrase IV (CA4), one of the enzymes composing the spliceosome which unwinds mRNAs to allow for spicing U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200), kelch-like protein 7 (KLHL7), a protein involved with the E3 ubiquitin ligase, and guanylate cyclase activator protein 1B (GCAP1B) which works to restore the dark current of the photoreceptors by increasing the production of cyclic guanidine monophosphate (Blanton et al., 1991; Chakarova et al., 2002, 2007; Friedman et al., 2009; Kajiwara et al., 1991; Keen et al., 1995; Makarova et al., 2002; Martinez-Gimeno et al., 2003; Sato et al., 2005; Schmidt-Kastner et al., 2008; van Lith-Verhoeven et al., 2002; Wada et al., 2001; Yang et al., 2005; Zhao et al., 2009). Animal models for ADRP mutations exist in many species including mouse, rat, fly, pig, and others.
Retinitis pigmentosa is a retinal degeneration transmitted by varied modes of inheritance and affects approximately 1 in 4000 individuals. The photoreceptors of the outer retina, as well as the retinal pigmented epithelium which supports the outer retina metabolically and structurally, are the retinal regions most affected by the disorder. In several forms of retinitis pigmentosa, the mislocalization of the rod photoreceptor protein rhodopsin is thought to be a contributing factor underlying the pathophysiology seen in patients. The mutations causing this mislocalization often occur in genes coding proteins involved in ciliary formation, vesicular transport, rod outer segment disc formation, and stability, as well as the rhodopsin protein itself. Often, these mutations result in the most early-onset cases of both recessive and dominant retinitis pigmentosa, and the following presents a discussion of the proteins, their degenerative phenotypes, and possible treatments of the disease.
Characterization of the human TBX20 gene, a new member of the T-box gene family closely related to the Drosophila H15 gene
2000, Genomics
T-box transcription factors contain a novel type of DNA-binding domain, the T-box domain, and are encoded by an ancient gene family. Four T-box genes, omb, Trg, org-1, and H15, have been identified in Drosophila, whereas in mammals the T-box gene family has expanded, and 12 human T-box genes have been isolated. We have identified a new human T-box gene, TBX20, and its mouse homologue Tbx20, which are more closely related to the Drosophila H15 gene than to any known vertebrate gene. H15 expression in leg imaginal discs correlates with commitment to a ventral fate, implicating this gene in early patterning events. We find that TBX20 is expressed in the fetal heart, eye, and limb, and during embryogenesis in the mouse, Tbx20 is expressed in the developing heart, eye, ventral neural tube, and limbs, indicating a possible role in regulating development of these tissues. The TBX20 gene maps to chromosome 7p14–p15. An association between TBX20 and loci for retinitis pigmentosa, RP9, and blepharophimosis syndrome, BPES, have been excluded.
Autosomal dominant distal spinal muscular atrophy type V (dSMA-V) and Charcot-Marie-Tooth disease type 2D (CMT2D) segregate within a single large kindred and map to a refined region on chromosome 7p15
1998, Journal of the Neurological Sciences
Two separate disorders, autosomal dominant distal spinal muscular atrophy type V (dSMA-V) characterized by marked bilateral weakness in the hands and atrophy of thenar eminence and the first interosseous muscle, and Charcot-Marie-Tooth disease type 2D (CMT2D) characterized by sensory deficits in addition to the upper limb weakness and wasting, have been independently linked to chromosome 7p. We identified a multigenerational Mongolian kindred with 17 members affected with either dSMA-V or CMT2D and mapped both syndromes to the same region on chromosome 7p15. A maximum two-point lod score of 4.74 at recombination fraction zero was obtained with marker D7S474. Tight linkage without recombination was also detected with markers D7S526 and D7S632. A multipoint lod score of 6.07 suggested that the gene is located between markers D7S526 and D7S474. A single conserved haplotype was associated with dSMA-V and CMT2D. Based on informative recombination events, the disease locus was placed between markers D7S516 and D7S1514 within the 7p15 band. Data obtained from this study suggest that a single gene is responsible for both syndromes, dSMA-V and CMT2D, and extend our knowledge of the candidate region.
Analysis of a human gene homologous to rat ventral prostate.1 protein
1997, Genomics
We report on the analysis of a human gene homologous to the rat ventral prostate.1 protein (RVP.1), which is transcriptionally induced in the regressing rat prostate after castration. EST database searching and Northern blotting reveal that this is one of at least four different members of a gene family in the human genome that produce transcripts of 3.4, 2.4, 1.9, and 1.2 kb, expressed in a wide range of tissues. Three other members of this gene family have already been mapped to chromosomes 7q, 17p, and 22q and reported either as anonymous ESTs or as full-length clones. We have now characterized a fourth member (assigned the gene name C7orf1 by GDB) and localized it also to chromosome 7q. C7orf1 is almost identical over much of its length to the reported ORF of RVP.1, while the other family members are more divergent from RVP.1. The genomic sequence of C7orf1 is intron-less, is spanned by a CpG low-methylation island, and has two noncoding, nonpolymorphic STR regions immediately adjacent to the open reading frame, one 5′ and one 3′. The presence of aNotI restriction site in the coding sequence results in a deficiency in the IMAGE cDNA libraries, as a result of which the 3′ end of the gene is not in the EST databases. The putative 220-amino-acid protein shows 89% identity to the amino terminus of rat RVP.1. Like rat RVP.1, it has four hydrophobic potential membrane-spanning regions, but it lacks 60 amino acid residues at its carboxyl terminus relative to rat RVP.1. Nevertheless, gene-specific primers from this transcript amplified a product in human cDNAs from several different tissues; its size corresponds to the 1.2-kb transcript seen on a Northern blot, and identical ESTs from several different tissues exist in the databases. It therefore seems likely that C7orf1 is the closest human homologue of rat RVP.1.
Evidence that the penetrance of mutations at the RP11 locus causing dominant retinitis pigmentosa is influenced by a gene linked to the homologous RP11 allele
1997, American Journal of Human Genetics
A subset of families with autosomal dominant retinitis pigmentosa (RP) display reduced penetrance with some asymptomatic gene carriers showing no retinal abnormalities by ophthalmic examination or by electroretinography. Here we describe a study of three families with reduced-penetrance RP. In all three families the disease gene appears to be linked to chromosome 19q13.4, the region containing the RP11 locus, as defined by previously reported linkage studies based on five other reduced-penetrance families. Meiotic recombinants in one of the newly identified RP11 families and in two of the previously reported families serve to restrict the disease locus to a 6-cM region bounded by markers D19S572 and D19S926. We also compared the disease status of RP11 carriers with the segregation of microsatellite alleles within 19q13.4 from the noncarrier parents in the newly reported and the previously reported families. The results support the hypothesis that wild-type alleles at the RP11 locus or at a closely linked locus inherited from the noncarrier parents are a major factor influencing the penetrance of pathogenic alleles at this locus.
Prioritization of Retinal Disease Genes: An Integrative Approach
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Regular ArticleA YAC Contig Spanning the Dominant Retinitis Pigmentosa Locus (RP9) on Chromosome 7p

Abstract

Regular Article
A YAC Contig Spanning the Dominant Retinitis Pigmentosa Locus (RP9) on Chromosome 7p