OMIA 001341-9796 : Night blindness, congenital stationary in Equus caballus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 613216

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Incompletely Dominant

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2011

Species-specific name: Leopard complex; Appaloosa; Congenital stationary night blindness

Species-specific symbol: LP; CSNB

Inheritance: As summarised by Bellone et al. (2013): "Leopard complex spotting is a group of white spotting patterns in horses caused by an incompletely dominant gene (LP) . . . homozygotes (LP/LP) are also affected with congenital stationary night blindness". Thus, a single mutation is autosomal incompletely dominant for Leopard Complex/Appaloosa and autosomal recessive for stationary congenital night blindness.

Mapping: A genome scan on 27 half-sibs segregating this trait, each genotyped with 102 microsatellites, enabled Terry et al. (2004) to linkage-map this trait to chromosome ECA1. Linkage analyses with additional markers on additional horses in the candidate region enabled Terry et al. (2004) to refine the location to a region of approximately 6cM "between microsatellite markers ASB08 and 1CA43". Comparative mapping analysis enabled Terry et al. (2004) to suggest TRPM1 (encoding transient receptor potential cation channel, subfamily M, member 1) as a potential comparative positional candidate gene. By judicial sequencing and SNP genotyping, Bellone et al. (2010) narrowed the candidate region to "A single 173 kb haplotype associated with LP and CSNB (ECA1: 108,197,355- 108,370,150)" which contains TRPM1.

From segregation analysis, Holl et al. (2016) concluded there is a major gene that modifies the extent of white in Leopard complex spotting. They mapped this gene, which they named PATN1 (for pattern-1), to a 15Mb region on chromosome ECA3p.

Molecular basis: RNA sequencing "from five samples (three from skin and two from retina)" enabled Bellone et al. (2011) to identify the causal mutation as a retroviral long terminal repeat (LTR) insertion in TRPM1. Details were provided by Bellone et al. (2013): the causal mutation is "a 1378 bp insertion in intron 1 of TRPM1".

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
TRPM1 transient receptor potential cation channel, subfamily M, member 1 Equus caballus 1 NC_009144.3 (109301575..109109527) TRPM1 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the required column headers

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
American Miniature Horse Appaloosa Australian Spotted Pony British Spotted Pony Knabstrupper Noriker Pony of the Americas Thoroughbred Stationary congenital night blindness & Leopard Complex/Appaloosa spotting TRPM1 insertion, gross (>20) EquCab2 1 g.108297929_108297930ins1378 "a 1378 bp retroviral LTR insertion in intron 1 of TRPM1" 2013 24167615

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2017 Bellone, R.R. :
Genetic Testing as a Tool to Identify Horses with or at Risk for Ocular Disorders. Vet Clin North Am Equine Pract 33:627-645, 2017. Pubmed reference: 29103563. DOI: 10.1016/j.cveq.2017.08.005.
2016 Holl, H.M., Brooks, S.A., Archer, S., Brown, K., Malvick, J., Penedo, M.C., Bellone, R.R. :
Variant in the RFWD3 gene associated with PATN1, a modifier of leopard complex spotting. Anim Genet 47:91-101, 2016. Pubmed reference: 26568529. DOI: 10.1111/age.12375.
2015 Ludwig, A., Reissmann, M., Benecke, N., Bellone, R., Sandoval-Castellanos, E., Cieslak, M., Fortes, G.G., Morales-Muñiz, A., Hofreiter, M., Pruvost, M. :
Twenty-five thousand years of fluctuating selection on leopard complex spotting and congenital night blindness in horses. Philos Trans R Soc Lond B Biol Sci 370:20130386, 2015. Pubmed reference: 25487337. DOI: 10.1098/rstb.2013.0386.
2013 Bellone, R.R., Holl, H., Setaluri, V., Devi, S., Maddodi, N., Archer, S., Sandmeyer, L., Ludwig, A., Foerster, D., Pruvost, M., Reissmann, M., Bortfeldt, R., Adelson, D.L., Lim, S.L., Nelson, J., Haase, B., Engensteiner, M., Leeb, T., Forsyth, G., Mienaltowski, M.J., Mahadevan, P., Hofreiter, M., Paijmans, J.L., Gonzalez-Fortes, G., Grahn, B., Brooks, S.A. :
Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse. PLoS One 8:e78280, 2013. Pubmed reference: 24167615. DOI: 10.1371/journal.pone.0078280.
2012 Sandmeyer, L.S., Bellone, R.R., Archer, S., Bauer, B.S., Nelson, J., Forsyth, G., Grahn, B.H. :
Congenital stationary night blindness is associated with the leopard complex in the Miniature Horse. Vet Ophthalmol 15:18-22, 2012. Pubmed reference: 22051042. DOI: 10.1111/j.1463-5224.2011.00903.x.
2011 Bellone, R.R., Holl, H., Nelson, J., Archer, S., Adelson, D., Sandmeyer, L., Haase, B., Engensteiner, M., Leeb, T., Forsyth, G., Grahn, B., Brooks, S.A. :
An Insertion In TRPM1, The Genetic Cause Of Leopard Complex (LP) Spotting And Congenital Stationary Night Blindness (CSNB) In Horses Plant & Animal Genomes XIX Conference :Abstract W204, 2011.
2010 Bellone, RR. :
Pleiotropic effects of pigmentation genes in horses. Anim Genet 41 Suppl 2:100-10, 2010. Pubmed reference: 21070283. DOI: 10.1111/j.1365-2052.2010.02116.x.
Bellone, RR., Forsyth, G., Leeb, T., Archer, S., Sigurdsson, S., Imsland, F., Mauceli, E., Engensteiner, M., Bailey, E., Sandmeyer, L., Grahn, B., Lindblad-Toh, K., Wade, CM. :
Fine-mapping and mutation analysis of TRPM1: a candidate gene for leopard complex (LP) spotting and congenital stationary night blindness in horses. Brief Funct Genomic Proteomic 9:193-207, 2010. Pubmed reference: 20353955. DOI: 10.1093/bfgp/elq002.
2009 Schmidt, T.M. :
Role of melastatin-related transient receptor potential channel TRPM1 in the retina: Clues from horses and mice. J Neurosci 29:11720-2, 2009. Pubmed reference: 19776258. DOI: 10.1523/JNEUROSCI.3275-09.2009.
2008 Bellone, RR., Brooks, SA., Sandmeyer, L., Murphy, BA., Forsyth, G., Archer, S., Bailey, E., Grahn, B. :
Differential gene expression of TRPM1, the potential cause of congenital stationary night blindness and coat spotting patterns (LP) in the Appaloosa horse (Equus caballus). Genetics 179:1861-70, 2008. Pubmed reference: 18660533. DOI: 10.1534/genetics.108.088807.
2007 Sandmeyer, LS., Breaux, CB., Archer, S., Grahn, BH. :
Clinical and electroretinographic characteristics of congenital stationary night blindness in the Appaloosa and the association with the leopard complex. Vet Ophthalmol 10:368-75, 2007. Pubmed reference: 17970998. DOI: 10.1111/j.1463-5224.2007.00572.x.
2006 Bellone, R., Lawson, S., Hunter, N., Archer, S., Bailey, E. :
Analysis of a SNP in exon 7 of equine OCA2 and its exclusion as a cause for appaloosa spotting. Anim Genet 37:525, 2006. Pubmed reference: 16978190. DOI: 10.1111/j.1365-2052.2006.01505.x.
Sandmeyer, LS., Grahn, BH., Breaux, CB. :
Diagnostic ophthalmology. Congenital stationary night blindness (CSNB). Can Vet J 47:1131, 1133, 2006. Pubmed reference: 17147148.
2005 Nunnery, C., Pickett, JP., Zimmerman, KL. :
Congenital stationary night blindness in a Thoroughbred and a Paso Fino. Vet Ophthalmol 8:415-9, 2005. Pubmed reference: 16359365. DOI: 10.1111/j.1463-5224.2005.00416.x.
2004 Terry, RB., Archer, S., Brooks, S., Bernoco, D., Bailey, E. :
Assignment of the appaloosa coat colour gene (LP) to equine chromosome 1. Anim Genet 35:134-7, 2004. Pubmed reference: 15025575. DOI: 10.1111/j.1365-2052.2004.01113.x.
2002 Terry, R.B., Bailey, E., Lear, T., Cothran, E.G. :
Rejection of MITF and MGF as the genes responsible for appaloosa coat colour patterns in horses Animal Genetics 33:82-84, 2002. Pubmed reference: 11849149.
2001 Terry, R.R., Bailey, E., Bernoco, D., Cothran, E.G. :
Linked markers exclude KIT as the gene responsible for appaloosa coat colour spotting patterns in horses Animal Genetics 32:98-101, 2001. Pubmed reference: 11421946.
1990 Sponenberg, D.P., Carr, G., Simak, E., Schwink, K. :
The Inheritance of the Leopard Complex of Spotting Patterns in Horses Journal of Heredity 81:323-331, 1990. Pubmed reference: 2177073.
1978 Witzel, DA., Smith, EL., Wilson, RD., Aguirre, GD. :
Congenital stationary night blindness: an animal model. Invest Ophthalmol Vis Sci 17:788-95, 1978. Pubmed reference: 308060.
1977 Joyce, J.R., Witzel, D.A. :
Equine night blindness. J Am Vet Med Assoc 170:878, 880, 1977. Pubmed reference: 301522.
Witzel, D.A., Joyce, J.R., Smith, E.L. :
Electroretinography of congenital night blindness in a filly Journal of Equine Medicine and Surgery 1:226-229, 1977.
Witzel, D.A., Riis, R.C., Rebhun, W.C., Hillman, R.B. :
Night blindness in the Appaloosa: sibling occurrence Journal of Equine Medicine and Surgery 1:383-386, 1977.

Edit History


  • Created by Frank Nicholas on 11 Feb 2011
  • Changed by Frank Nicholas on 11 Sep 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 01 Nov 2013
  • Changed by Frank Nicholas on 02 Jun 2016
  • Changed by Frank Nicholas on 03 Nov 2016
  • Changed by Frank Nicholas on 12 Dec 2017