IOVS MS 11-7777 (Article 2207) Proofs Available _______________________ Dear Author: The proofs of your article above are available for your review. Please download the file located at this URLaddress: http://rapidproof.cadmus.com/RapidProof/retrieval/index.jsp Login: [your e-mail address]Password: 99S4UntgTcU9 You will need to have Adobe Acrobat Reader software to read this file. This is free software and is availablefor user downloading at http://www.adobe.com/products/acrobat/readstep.html. If you experience technical problems, please contact Tracey Ritchey(e-mail: ritcheyt@cadmus.com; phone: 717-721-2646) This file contains: -- Instructions to Author-- Adobe Acrobat Comments and Notes Instructions-- Publication Fees and Reprint Order Form-- Page Proofs for your article, table of contents precis blurb, and author queries - containing 5 pages Please insert your comments electronically (instructions enclosed), or print the PDF proofs and add yourcomments manually. Follow the enclosed instructions for emailing, faxing, or mailing your corrections.Return all materials within 48 hours (two business days) to assure quick publication of your article. NOTE: Effective with the January 2010 issue IOVS will be available online only. No printed issues will beproduced. Printed reprints may still be ordered using the file provided. If you have any questions regarding your article, please contact me. ALWAYS INCLUDE YOURARTICLE NO. (IOVS MS 11-7777) WITH ALL CORRESPONDENCE. Cathy FreyTel: 717-721-2616Fax: 717-738-9479 or 717-738-9478freyc@cadmus.com

/pdf/investigative-ophthalmology-and-visual-science-2azo1n1ewx.pdf

Investigative Ophthalmology and Visual Science

Stargardt disease (STGD, also known as fundus flavimaculatus; FFM) is an autosomal recessive retinal disorder characterized by a juvenile-onset macular dystrophy, alterations of the peripheral retina, and subretinal deposition of lipofuscin-like material A gene encoding an ATP-binding cassette (ABC) transporter was mapped to the 2-cM (centiMorgan) interval at 1p13-p21 previously shown by linkage analysis to harbour the STGD gene This gene, ABCR, is expressed exclusively and at high levels in the retina, in rod but not cone photoreceptors, as detected by in situ hybridization Mutational analysis of ABCR in STGD families revealed a total of 19 different mutations including homozygous mutations in two families with consanguineous parentage These data indicate that ABCR is the causal gene of STGD/FFM

A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy

This paper presents the 12th update of the human obesity gene map, which incorporates published results up to the end of October 2005. Evidence from single-gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, transgenic and knockout murine models relevant to obesity, quantitative trait loci (QTL) from animal cross-breeding experiments, association studies with candidate genes, and linkages from genome scans is reviewed. As of October 2005, 176 human obesity cases due to single-gene mutations in 11 different genes have been reported, 50 loci related to Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and causal genes or strong candidates have been identified for most of these syndromes. There are 244 genes that, when mutated or expressed as transgenes in the mouse, result in phenotypes that affect body weight and adiposity. The number of QTLs reported from animal models currently reaches 408. The number of human obesity QTLs derived from genome scans continues to grow, and we now have 253 QTLs for obesity-related phenotypes from 61 genome-wide scans. A total of 52 genomic regions harbor QTLs supported by two or more studies. The number of studies reporting associations between DNA sequence variation in specific genes and obesity phenotypes has also increased considerably, with 426 findings of positive associations with 127 candidate genes. A promising observation is that 22 genes are each supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. The electronic version of the map with links to useful publications and relevant sites can be found at http://obesitygene.pbrc.edu.

/pdf/the-human-obesity-gene-map-the-2005-update-3zvtci1u6f.pdf

The human obesity gene map: the 2005 update.

Cilia and flagella are ancient, evolutionarily conserved organelles that project from cell surfaces to perform diverse biological roles, including whole-cell locomotion; movement of fluid; chemo-, mechano-, and photosensation; and sexual reproduction Consistent with their stringent evolutionary conservation, defects in cilia are associated with a range of human diseases, such as primary ciliary dyskinesia, hydrocephalus, polycystic liver and kidney disease, and some forms of retinal degeneration Recent evidence indicates that ciliary defects can lead to a broader set of developmental and adult phenotypes, with mutations in ciliary proteins now associated with nephronophthisis, Bardet-Biedl syndrome, Alstrom syndrome, and Meckel-Gruber syndrome The molecular data linking seemingly unrelated clinical entities are beginning to highlight a common theme, where defects in ciliary structure and function can lead to a predictable phenotypic pattern that has potentially predictive and therapeutic value

https://www.annualreviews.org/doi/pdf/10.1146/annurev.genom.7.080505.115610

The Ciliopathies: An Emerging Class of Human Genetic Disorders

This paper presents the eleventh update of the human obesity gene map, which incorporates published results up to the end of October 2004. Evidence from single-gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, transgenic and knockout murine models relevant to obesity, quantitative trait loci (QTLs) from animal cross-breeding experiments, association studies with candidate genes, and linkages from genome scans is reviewed. As of October 2004, 173 human obesity cases due to single-gene mutations in 10 different genes have been reported, and 49 loci related to Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and causal genes or strong candidates have been identified for most of these syndromes. There are 166 genes which, when mutated or expressed as transgenes in the mouse, result in phenotypes that affect body weight and adiposity. The number of QTLs reported from animal models currently reaches 221. The number of human obesity QTLs derived from genome scans continues to grow, and we have now 204 QTLs for obesity-related phenotypes from 50 genome-wide scans. A total of 38 genomic regions harbor QTLs replicated among two to four studies. The number of studies reporting associations between DNA sequence variation in specific genes and obesity phenotypes has also increased considerably with 358 findings of positive associations with 113 candidate genes. Among them, 18 genes are supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. Overall, >600 genes, markers, and chromosomal regions have been associated or linked with human obesity phenotypes. The electronic version of the map with links to useful publications and genomic and other relevant sites can be found at http://obesitygene.pbrc.edu.

https://onlinelibrary.wiley.com/doi/pdf/10.1038/oby.2005.50

The human obesity gene map: the 2004 update.

X-linked retinitis pigmentosa (xlRP) is a severe progressive retinal degeneration which affects about 1 in 25,000 of the population. The most common form of xlRP, RP3, has been localised to the interval between CYBB and OTC in Xp21.1 by linkage analysis and deletion mapping. Identification of microdeletions within this region has now led to the positional cloning of a gene, RPGR, that spans 60 kg of genomic DNA and is ubiquitously expressed. The predicted 90 kD protein contains in its N-terminal half a tandem repeat structure highly similar to RCC1 (regulator of chromosome condensation), suggesting an interaction with a small GTPase. The C-terminal half contains a domain, rich in acidic residues, and ends in a potential isoprenylation anchorage site. The two intragenic deletions, two nonsense and three missense mutations within conserved domains provide evidence that RPGR (retinitis pigmentosa GTPase regulator) is the RP3 gene.

K. Porter

Papers

A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3).

Linkage mapping in 29 Bardet-Biedl syndrome families confirms loci in chromosomal regions 11q13, 15q22.3-q23, and 16q21.