Fine-mapping and mutation analysis of TRPM1: A candidate gene for leopard complex (LP) spotting and congenital stationary night blindness in horses

Rebecca Bellone, George Forsyth, Tosso Leeb, Sheila Archer, Snaevar Sigurdsson, Freyja Imsland, Evan Mauceli, Martina Engensteiner, Ernest Bailey, Lynne Sandmeyer, Bruce Grahn, Kerstin Lindblad-Toh, Claire M. Wade

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Leopard Complex spotting occurs in several breeds of horses and is caused by an incompletely dominant allele (LP). Homozygosity for LP is also associated with congenital stationary night blindness (CSNB) in Appaloosa horses. Previously, LP was mapped to a 6 cm region on ECA1 containing the candidate gene TRPM1 (Transient Receptor Potential Cation Channel, Subfamily M, Member 1) and decreased expression of this gene, measured by qRT-PCR, was identified as the likely cause of both spotting and ocular phenotypes. This study describes investigations for a muta-tion causing or associated with the Leopard Complex and CSNB phenotype in horses. Re-sequencing of the gene and associated splice sites within the 105 624 bp genomic region of TRPM1 led to the discovery of 18 SNPs. Most of the SNPs did not have a predictive value for the presence of LP. However, one SNP (ECA1:108,249,293 C>T) found within intron 11 had a strong (P < 0.0005), but not complete, association with LP and CSNB and thus is a good marker but unlikely to be causative. To further localize the association, 70 SNPs spanning over two Mb including the TRPM1 gene were genotyped in 192 horses from three different breeds segregating for LP. Asingle 173 kb haplo-type associated with LP and CSNB (ECA1: 108,197,355- 108,370,150) was identified. Illumina sequencing of 300 kb sur-rounding this haplotype revealed 57 SNP variants. Based on their localization within expressed sequences or regions of high sequence conservation across mammals, six of these SNPs were considered to be the most likelycan-didate mutations. While the precise function of TRPM1 remains to be elucidated, this work solidifies its functional role in both pigmentation and night vision. Further, this work has identified several potential regulatory elements of the TRPM1 gene that should be investigated further in this and other species.

Original languageEnglish (US)
Article numberelq002
Pages (from-to)193-207
Number of pages15
JournalBriefings in Functional Genomics and Proteomics
Volume9
Issue number3
DOIs
StatePublished - Mar 29 2010
Externally publishedYes

Fingerprint

Panthera
Metrorrhagia
Horses
Genes
Mutation
Single Nucleotide Polymorphism
Transient Receptor Potential Channels
Mammals
Introns
Conservation
Night Vision
Phenotype
Congenital stationary night blindness
Pigmentation
Haplotypes
Alleles

Keywords

  • Congenital stationary night blindness
  • Fine mapping
  • Illumina DNA sequencing
  • Leopard Complex spotting
  • Member I
  • Subfamily M
  • Transient receptor potential cation channel

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Fine-mapping and mutation analysis of TRPM1 : A candidate gene for leopard complex (LP) spotting and congenital stationary night blindness in horses. / Bellone, Rebecca; Forsyth, George; Leeb, Tosso; Archer, Sheila; Sigurdsson, Snaevar; Imsland, Freyja; Mauceli, Evan; Engensteiner, Martina; Bailey, Ernest; Sandmeyer, Lynne; Grahn, Bruce; Lindblad-Toh, Kerstin; Wade, Claire M.

In: Briefings in Functional Genomics and Proteomics, Vol. 9, No. 3, elq002, 29.03.2010, p. 193-207.

Research output: Contribution to journalArticle

Bellone, R, 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 2010, 'Fine-mapping and mutation analysis of TRPM1: A candidate gene for leopard complex (LP) spotting and congenital stationary night blindness in horses', Briefings in Functional Genomics and Proteomics, vol. 9, no. 3, elq002, pp. 193-207. https://doi.org/10.1093/bfgp/elq002
Bellone, Rebecca ; Forsyth, George ; Leeb, Tosso ; Archer, Sheila ; Sigurdsson, Snaevar ; Imsland, Freyja ; Mauceli, Evan ; Engensteiner, Martina ; Bailey, Ernest ; Sandmeyer, Lynne ; Grahn, Bruce ; Lindblad-Toh, Kerstin ; Wade, Claire M. / Fine-mapping and mutation analysis of TRPM1 : A candidate gene for leopard complex (LP) spotting and congenital stationary night blindness in horses. In: Briefings in Functional Genomics and Proteomics. 2010 ; Vol. 9, No. 3. pp. 193-207.
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abstract = "Leopard Complex spotting occurs in several breeds of horses and is caused by an incompletely dominant allele (LP). Homozygosity for LP is also associated with congenital stationary night blindness (CSNB) in Appaloosa horses. Previously, LP was mapped to a 6 cm region on ECA1 containing the candidate gene TRPM1 (Transient Receptor Potential Cation Channel, Subfamily M, Member 1) and decreased expression of this gene, measured by qRT-PCR, was identified as the likely cause of both spotting and ocular phenotypes. This study describes investigations for a muta-tion causing or associated with the Leopard Complex and CSNB phenotype in horses. Re-sequencing of the gene and associated splice sites within the 105 624 bp genomic region of TRPM1 led to the discovery of 18 SNPs. Most of the SNPs did not have a predictive value for the presence of LP. However, one SNP (ECA1:108,249,293 C>T) found within intron 11 had a strong (P < 0.0005), but not complete, association with LP and CSNB and thus is a good marker but unlikely to be causative. To further localize the association, 70 SNPs spanning over two Mb including the TRPM1 gene were genotyped in 192 horses from three different breeds segregating for LP. Asingle 173 kb haplo-type associated with LP and CSNB (ECA1: 108,197,355- 108,370,150) was identified. Illumina sequencing of 300 kb sur-rounding this haplotype revealed 57 SNP variants. Based on their localization within expressed sequences or regions of high sequence conservation across mammals, six of these SNPs were considered to be the most likelycan-didate mutations. While the precise function of TRPM1 remains to be elucidated, this work solidifies its functional role in both pigmentation and night vision. Further, this work has identified several potential regulatory elements of the TRPM1 gene that should be investigated further in this and other species.",
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