Evidence for a Retroviral Insertion in TRPM1 as the Cause of Congenital Stationary Night Blindness and Leopard Complex Spotting in the Horse

Rebecca R. Bellone; Heather Holl; Vijayasaradhi Setaluri; Sulochana Devi; Nityanand Maddodi; Sheila Archer; Lynne Sandmeyer; Arne Ludwig; Daniel Foerster; Melanie Pruvost; Monika Reissmann; Ralf Bortfeldt; David L. Adelson; Sim Lin Lim; Janelle Nelson; Bianca Haase; Martina Engensteiner; Tosso Leeb; George Forsyth; Michael J. Mienaltowski; Padmanabhan Mahadevan; Michael Hofreiter; Johanna L. A. Paijmans; Gloria Gonzalez-Fortes; Bruce Grahn; Samantha A. Brooks

doi:10.1371/journal.pone.0078280

Evidence for a Retroviral Insertion in TRPM1 as the Cause of Congenital Stationary Night Blindness and Leopard Complex Spotting in the Horse

Rebecca R. Bellone
, Heather Holl
, Vijayasaradhi Setaluri
, Sulochana Devi
, Nityanand Maddodi
, Sheila Archer
, Lynne Sandmeyer
, Arne Ludwig
, Daniel Foerster
, Melanie Pruvost
, Monika Reissmann
, Ralf Bortfeldt
, David L. Adelson
, Sim Lin Lim
, Janelle Nelson
, Bianca Haase
, Martina Engensteiner
, Tosso Leeb
, George Forsyth
, Michael J. Mienaltowski

Padmanabhan Mahadevan, Michael Hofreiter, Johanna L. A. Paijmans, Gloria Gonzalez-Fortes, Bruce Grahn, Samantha A. Brooks

University of Tampa
Cornell University
University of Wisconsin
University of Saskatchewan
Leibniz Institute for Zoo and Wildlife Research
Humboldt-University, Berlin
University of Adelaide
University of Sydney
University of Bern
University of South Florida
University of York

Research output: Contribution to journal › Article › peer-review

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 (χ2=1022.00, p<<0.0005), and CSNB, testing 43 horses (χ2=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.

Original language	Unknown
Pages (from-to)	e78280
Journal	PLoS ONE
Volume	8
Issue number	10
DOIs	https://doi.org/10.1371/journal.pone.0078280
Publication status	Published - 22 Oct 2013
Externally published	Yes

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10.1371/journal.pone.0078280Licence: CC BY

Cite this

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., ... Brooks, S. A. (2013). 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(10), e78280. https://doi.org/10.1371/journal.pone.0078280

@article{2e56d7ffad8c4d4c87c5fff549114cf1,

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 (χ2=1022.00, p<<0.0005), and CSNB, testing 43 horses (χ2=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.",

author = "Bellone, \{Rebecca R.\} and Heather Holl and Vijayasaradhi Setaluri and Sulochana Devi and Nityanand Maddodi and Sheila Archer and Lynne Sandmeyer and Arne Ludwig and Daniel Foerster and Melanie Pruvost and Monika Reissmann and Ralf Bortfeldt and Adelson, \{David L.\} and Lim, \{Sim Lin\} and Janelle Nelson and Bianca Haase and Martina Engensteiner and Tosso Leeb and George Forsyth and Mienaltowski, \{Michael J.\} and Padmanabhan Mahadevan and Michael Hofreiter and Paijmans, \{Johanna L. A.\} and Gloria Gonzalez-Fortes and Bruce Grahn and Brooks, \{Samantha A.\}",

year = "2013",

month = oct,

day = "22",

doi = "10.1371/journal.pone.0078280",

language = "Anadnabyddus",

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Bellone, RR, Holl, H, Setaluri, V, Devi, S, Maddodi, N, Archer, S, Sandmeyer, L, Ludwig, A, Foerster, D, Pruvost, M, Reissmann, M, Bortfeldt, R, Adelson, DL, Lim, SL, Nelson, J, Haase, B, Engensteiner, M, Leeb, T, Forsyth, G, Mienaltowski, MJ, Mahadevan, P, Hofreiter, M, Paijmans, JLA, Gonzalez-Fortes, G, Grahn, B & Brooks, SA 2013, 'Evidence for a Retroviral Insertion in TRPM1 as the Cause of Congenital Stationary Night Blindness and Leopard Complex Spotting in the Horse', PLoS ONE, vol. 8, no. 10, pp. e78280. https://doi.org/10.1371/journal.pone.0078280

TY - JOUR

T1 - Evidence for a Retroviral Insertion in TRPM1 as the Cause of Congenital Stationary Night Blindness and Leopard Complex Spotting in the Horse

AU - Bellone, Rebecca R.

AU - Holl, Heather

AU - Setaluri, Vijayasaradhi

AU - Devi, Sulochana

AU - Maddodi, Nityanand

AU - Archer, Sheila

AU - Sandmeyer, Lynne

AU - Ludwig, Arne

AU - Foerster, Daniel

AU - Pruvost, Melanie

AU - Reissmann, Monika

AU - Bortfeldt, Ralf

AU - Adelson, David L.

AU - Lim, Sim Lin

AU - Nelson, Janelle

AU - Haase, Bianca

AU - Engensteiner, Martina

AU - Leeb, Tosso

AU - Forsyth, George

AU - Mienaltowski, Michael J.

AU - Mahadevan, Padmanabhan

AU - Hofreiter, Michael

AU - Paijmans, Johanna L. A.

AU - Gonzalez-Fortes, Gloria

AU - Grahn, Bruce

AU - Brooks, Samantha A.

PY - 2013/10/22

Y1 - 2013/10/22

N2 - 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 (χ2=1022.00, p<<0.0005), and CSNB, testing 43 horses (χ2=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.

AB - 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 (χ2=1022.00, p<<0.0005), and CSNB, testing 43 horses (χ2=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.

U2 - 10.1371/journal.pone.0078280

DO - 10.1371/journal.pone.0078280

M3 - Erthygl

SN - 1932-6203

VL - 8

SP - e78280

JO - PLoS ONE

JF - PLoS ONE

IS - 10

ER -