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
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.
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U2 - 10.1371/journal.pone.0078280
DO - 10.1371/journal.pone.0078280
M3 - Article
C2 - 24167615
AN - SCOPUS:84886061966
VL - 8
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 10
M1 - e78280
ER -