A major locus for autosomal recessive retinitis pigmentosa on 6q, determined by homozygosity mapping of chromosomal regions that contain gamma-aminobutyric acid-receptor clusters. (original) (raw)

Am J Hum Genet. 1998 Jun; 62(6): 1452–1459.

Unidad de Genética, Hospital Universitario "Virgen del Rocío," Seville, Spain.

Abstract

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy, with extensive allelic and nonallelic genetic heterogeneity. Autosomal recessive RP (arRP) is the most common form of RP worldwide, with at least nine loci known and accountable for approximately 10%-15% of all cases. Gamma-aminobutyric acid (GABA) is the major inhibitory transmitter in the CNS. Different GABA receptors are expressed in all retinal layers, and inhibition mediated by GABA receptors in the human retina could be related to RP. We have selected chromosomal regions containing genes that encode the different subunits of the GABA receptors, for homozygosity mapping in inbred families affected by arRP. We identify a new locus for arRP, on chromosome 6, between markers D6S257 and D6S1644. Our data suggest that 10%-20% of Spanish families affected by typical arRP could have linkage to this new locus. This region contains subunits GABRR1 and GABRR2 of the GABA-C receptor, which is the effector of lateral inhibition at the retina.

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Selected References

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Bormann J, Feigenspan A. GABAC receptors. Trends Neurosci. 1995 Dec;18(12):515–519. [PubMed] [Google Scholar]
Cutting GR, Curristin S, Zoghbi H, O'Hara B, Seldin MF, Uhl GR. Identification of a putative gamma-aminobutyric acid (GABA) receptor subunit rho2 cDNA and colocalization of the genes encoding rho2 (GABRR2) and rho1 (GABRR1) to human chromosome 6q14-q21 and mouse chromosome 4. Genomics. 1992 Apr;12(4):801–806. [PubMed] [Google Scholar]
Cutting GR, Lu L, O'Hara BF, Kasch LM, Montrose-Rafizadeh C, Donovan DM, Shimada S, Antonarakis SE, Guggino WB, Uhl GR, et al. Cloning of the gamma-aminobutyric acid (GABA) rho 1 cDNA: a GABA receptor subunit highly expressed in the retina. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2673–2677. [PMC free article] [PubMed] [Google Scholar]
DeLorey TM, Olsen RW. Gamma-aminobutyric acidA receptor structure and function. J Biol Chem. 1992 Aug 25;267(24):16747–16750. [PubMed] [Google Scholar]
Dib C, Fauré S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, Marc S, Hazan J, Seboun E, et al. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. [PubMed] [Google Scholar]
Dryja TP. Human genetics. Deficiencies in sight with the candidate gene approach. Nature. 1990 Oct 18;347(6294):614–614. [PubMed] [Google Scholar]
Dryja TP, Finn JT, Peng YW, McGee TL, Berson EL, Yau KW. Mutations in the gene encoding the alpha subunit of the rod cGMP-gated channel in autosomal recessive retinitis pigmentosa. Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10177–10181. [PMC free article] [PubMed] [Google Scholar]
Dryja TP, Li T. Molecular genetics of retinitis pigmentosa. Hum Mol Genet. 1995;4(Spec No):1739–1743. [PubMed] [Google Scholar]
Farrall M. Homozygosity mapping: familiarity breeds debility. Nat Genet. 1993 Oct;5(2):107–108. [PubMed] [Google Scholar]
Fukai K, Oh J, Karim MA, Moore KJ, Kandil HH, Ito H, Bürger J, Spritz RA. Homozygosity mapping of the gene for Chediak-Higashi syndrome to chromosome 1q42-q44 in a segment of conserved synteny that includes the mouse beige locus (bg). Am J Hum Genet. 1996 Sep;59(3):620–624. [PMC free article] [PubMed] [Google Scholar]
Gladwin A, Donnai D, Metcalfe K, Schrander-Stumpel C, Brueton L, Verloes A, Aylsworth A, Toriello H, Winter R, Dixon M. Localization of a gene for oculodentodigital syndrome to human chromosome 6q22-q24. Hum Mol Genet. 1997 Jan;6(1):123–127. [PubMed] [Google Scholar]
Gschwend M, Levran O, Kruglyak L, Ranade K, Verlander PC, Shen S, Faure S, Weissenbach J, Altay C, Lander ES, et al. A locus for Fanconi anemia on 16q determined by homozygosity mapping. Am J Hum Genet. 1996 Aug;59(2):377–384. [PMC free article] [PubMed] [Google Scholar]
Gu SM, Thompson DA, Srikumari CR, Lorenz B, Finckh U, Nicoletti A, Murthy KR, Rathmann M, Kumaramanickavel G, Denton MJ, et al. Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy. Nat Genet. 1997 Oct;17(2):194–197. [PubMed] [Google Scholar]
Huang SH, Pittler SJ, Huang X, Oliveira L, Berson EL, Dryja TP. Autosomal recessive retinitis pigmentosa caused by mutations in the alpha subunit of rod cGMP phosphodiesterase. Nat Genet. 1995 Dec;11(4):468–471. [PubMed] [Google Scholar]
Inglehearn CF. Intelligent linkage analysis using gene density estimates. Nat Genet. 1997 May;16(1):15–15. [PubMed] [Google Scholar]
Kelsell RE, Godley BF, Evans K, Tiffin PA, Gregory CY, Plant C, Moore AT, Bird AC, Hunt DM. Localization of the gene for progressive bifocal chorioretinal atrophy (PBCRA) to chromosome 6q. Hum Mol Genet. 1995 Sep;4(9):1653–1656. [PubMed] [Google Scholar]
Knowles JA, Shugart Y, Banerjee P, Gilliam TC, Lewis CA, Jacobson SG, Ott J. Identification of a locus, distinct from RDS-peripherin, for autosomal recessive retinitis pigmentosa on chromosome 6p. Hum Mol Genet. 1994 Aug;3(8):1401–1403. [PubMed] [Google Scholar]
Kolb H. The connections between horizontal cells and photoreceptors in the retina of the cat: electron microscopy of Golgi preparations. J Comp Neurol. 1974 May 1;155(1):1–14. [PubMed] [Google Scholar]
Kolb H. The architecture of functional neural circuits in the vertebrate retina. The Proctor Lecture. Invest Ophthalmol Vis Sci. 1994 Apr;35(5):2385–2404. [PubMed] [Google Scholar]
Kruglyak L, Daly MJ, Lander ES. Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping. Am J Hum Genet. 1995 Feb;56(2):519–527. [PMC free article] [PubMed] [Google Scholar]
Lander ES, Botstein D. Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. Science. 1987 Jun 19;236(4808):1567–1570. [PubMed] [Google Scholar]
Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med. 1994 Mar 3;330(9):613–622. [PubMed] [Google Scholar]
Lisman J, Fain G. Support for the equivalent light hypothesis for RP. Nat Med. 1995 Dec;1(12):1254–1255. [PubMed] [Google Scholar]
Lukasiewicz PD. GABAC receptors in the vertebrate retina. Mol Neurobiol. 1996 Jun;12(3):181–194. [PubMed] [Google Scholar]
Martínez-Mir A, Bayés M, Vilageliu L, Grinberg D, Ayuso C, del Río T, García-Sandoval B, Bussaglia E, Baiget M, Gonzàlez-Duarte R, et al. A new locus for autosomal recessive retinitis pigmentosa (RP19) maps to 1p13-1p21. Genomics. 1997 Feb 15;40(1):142–146. [PubMed] [Google Scholar]
Maw MA, Kennedy B, Knight A, Bridges R, Roth KE, Mani EJ, Mukkadan JK, Nancarrow D, Crabb JW, Denton MJ. Mutation of the gene encoding cellular retinaldehyde-binding protein in autosomal recessive retinitis pigmentosa. Nat Genet. 1997 Oct;17(2):198–200. [PubMed] [Google Scholar]
McLaughlin ME, Sandberg MA, Berson EL, Dryja TP. Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa. Nat Genet. 1993 Jun;4(2):130–134. [PubMed] [Google Scholar]
Pastural E, Barrat FJ, Dufourcq-Lagelouse R, Certain S, Sanal O, Jabado N, Seger R, Griscelli C, Fischer A, de Saint Basile G. Griscelli disease maps to chromosome 15q21 and is associated with mutations in the myosin-Va gene. Nat Genet. 1997 Jul;16(3):289–292. [PubMed] [Google Scholar]
Rapaport DH. Quantitative aspects of synaptic ribbon formation in the outer plexiform layer of the developing cat retina. Vis Neurosci. 1989 Jul;3(1):21–32. [PubMed] [Google Scholar]
Rosenfeld PJ, Cowley GS, McGee TL, Sandberg MA, Berson EL, Dryja TP. A null mutation in the rhodopsin gene causes rod photoreceptor dysfunction and autosomal recessive retinitis pigmentosa. Nat Genet. 1992 Jun;1(3):209–213. [PubMed] [Google Scholar]
Wilcox AS, Warrington JA, Gardiner K, Berger R, Whiting P, Altherr MR, Wasmuth JJ, Patterson D, Sikela JM. Human chromosomal localization of genes encoding the gamma 1 and gamma 2 subunits of the gamma-aminobutyric acid receptor indicates that members of this gene family are often clustered in the genome. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5857–5861. [PMC free article] [PubMed] [Google Scholar]
Schuler GD, Boguski MS, Stewart EA, Stein LD, Gyapay G, Rice K, White RE, Rodriguez-Tomé P, Aggarwal A, Bajorek E, et al. A gene map of the human genome. Science. 1996 Oct 25;274(5287):540–546. [PubMed] [Google Scholar]
Sivilotti L, Nistri A. GABA receptor mechanisms in the central nervous system. Prog Neurobiol. 1991;36(1):35–92. [PubMed] [Google Scholar]
Small KW, Weber JL, Roses A, Lennon F, Vance JM, Pericak-Vance MA. North Carolina macular dystrophy is assigned to chromosome 6. Genomics. 1992 Jul;13(3):681–685. [PubMed] [Google Scholar]
Stone EM, Nichols BE, Kimura AE, Weingeist TA, Drack A, Sheffield VC. Clinical features of a Stargardt-like dominant progressive macular dystrophy with genetic linkage to chromosome 6q. Arch Ophthalmol. 1994 Jun;112(6):765–772. [PubMed] [Google Scholar]
Tanaka K, Watase K, Manabe T, Yamada K, Watanabe M, Takahashi K, Iwama H, Nishikawa T, Ichihara N, Kikuchi T, et al. Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science. 1997 Jun 13;276(5319):1699–1702. [PubMed] [Google Scholar]
van Soest S, van den Born LI, Gal A, Farrar GJ, Bleeker-Wagemakers LM, Westerveld A, Humphries P, Sandkuijl LA, Bergen AA. Assignment of a gene for autosomal recessive retinitis pigmentosa (RP12) to chromosome 1q31-q32.1 in an inbred and genetically heterogeneous disease population. Genomics. 1994 Aug;22(3):499–504. [PubMed] [Google Scholar]

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