title: Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse.
abstract: Leopard complex spotting is a group of white spotting patterns in horses caused by an incompletely dominant gene (LP) where homozygotes (LP/LP) are also affected with congenital stationary night blindness. Previous studies implicated Transient Receptor Potential Cation Channel, Subfamily M, Member 1 (TRPM1) as the best candidate gene for both CSNB and LP. RNA-Seq data pinpointed a 1378 bp insertion in intron 1 of TRPM1 as the potential cause. This insertion, a long terminal repeat (LTR) of an endogenous retrovirus, was completely associated with LP, testing 511 horses (χ(2)=1022.00, p<<0.0005), and CSNB, testing 43 horses (χ(2)=43, p<<0.0005). The LTR was shown to disrupt TRPM1 transcription by premature poly-adenylation. Furthermore, while deleterious transposable element insertions should be quickly selected against the identification of this insertion in three ancient DNA samples suggests it has been maintained in the horse gene pool for at least 17,000 years. This study represents the first description of an LTR insertion being associated with both a pigmentation phenotype and an eye disorder.
authors.affiliation: Department of Biology, University of Tampa, Tampa, Florida, United States of America.
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Bellone
authors.forename: Heather
authors.initials: H
authors.lastname: Holl
authors.forename: Vijayasaradhi
authors.initials: V
authors.lastname: Setaluri
authors.forename: Sulochana
authors.initials: S
authors.lastname: Devi
authors.forename: Nityanand
authors.initials: N
authors.lastname: Maddodi
authors.forename: Sheila
authors.initials: S
authors.lastname: Archer
authors.forename: Lynne
authors.initials: L
authors.lastname: Sandmeyer
authors.forename: Arne
authors.initials: A
authors.lastname: Ludwig
authors.forename: Daniel
authors.initials: D
authors.lastname: Foerster
authors.forename: Melanie
authors.initials: M
authors.lastname: Pruvost
authors.forename: Monika
authors.initials: M
authors.lastname: Reissmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Bortfeldt
authors.forename: David L
authors.initials: DL
authors.lastname: Adelson
authors.forename: Sim Lin
authors.initials: SL
authors.lastname: Lim
authors.forename: Janelle
authors.initials: J
authors.lastname: Nelson
authors.forename: Bianca
authors.initials: B
authors.lastname: Haase
authors.forename: Martina
authors.initials: M
authors.lastname: Engensteiner
authors.forename: Tosso
authors.initials: T
authors.lastname: Leeb
authors.forename: George
authors.initials: G
authors.lastname: Forsyth
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mienaltowski
authors.forename: Padmanabhan
authors.initials: P
authors.lastname: Mahadevan
authors.forename: Michael
authors.initials: M
authors.lastname: Hofreiter
authors.forename: Johanna L A
authors.initials: JL
authors.lastname: Paijmans
authors.forename: Gloria
authors.initials: G
authors.lastname: Gonzalez-Fortes
authors.forename: Bruce
authors.initials: B
authors.lastname: Grahn
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Brooks
mesh_terms: D000818:Animals; D005260:Female; D006734:Horse Diseases / Q000235:genetics*; D006736:Horses; D008297:Male; D016254:Mutagenesis, Insertional; D009755:Night Blindness / Q000235:genetics* / Q000378:metabolism / Q000662:veterinary*; D018626:Retroelements; D012190:Retroviridae / Q000235:genetics*; D012880:Skin Pigmentation / Q000235:genetics*; D050053:TRPM Cation Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D018626:Retroelements; D050053:TRPM Cation Channels