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Length variations within the Merle retrotransposon of canine PMEL: correlating genotype with phenotype
BACKGROUND: The antisense insertion of a canine short interspersed element (SINEC_Cf) in the pigmentation gene PMEL (or SILV) causes a coat pattern phenotype in dogs termed merle. Merle is a semi-dominant trait characterized by patches of full pigmentation on a diluted background. The oligo(dT) trac...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091007/ https://www.ncbi.nlm.nih.gov/pubmed/30123327 http://dx.doi.org/10.1186/s13100-018-0131-6 |
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author | Murphy, Sarah C. Evans, Jacquelyn M. Tsai, Kate L. Clark, Leigh Anne |
author_facet | Murphy, Sarah C. Evans, Jacquelyn M. Tsai, Kate L. Clark, Leigh Anne |
author_sort | Murphy, Sarah C. |
collection | PubMed |
description | BACKGROUND: The antisense insertion of a canine short interspersed element (SINEC_Cf) in the pigmentation gene PMEL (or SILV) causes a coat pattern phenotype in dogs termed merle. Merle is a semi-dominant trait characterized by patches of full pigmentation on a diluted background. The oligo(dT) tract of the Merle retrotransposon is long and uninterrupted and is prone to dramatic truncation. Phenotypically wild-type individuals carrying shorter oligo(dT) lengths of the Merle allele have been previously described and termed cryptic merles. Two additional coat patterns, dilute merle (uniform, steely-grey coat) and harlequin merle (white background with black patches), also appear in breeds segregating the Merle allele. RESULTS: Sequencing of all PMEL exons in a dilute and a harlequin merle reveals that variation exists solely within the oligo(dT) tract of the SINEC_Cf insertion. In fragment analyses from 259 dogs heterozygous for Merle, we observed a spectrum of oligo(dT) lengths spanning 25 to 105 base pairs (bp), with ranges that correspond to the four varieties of the merle phenotype: cryptic (25–55 bp), dilute (66–74 bp), standard (78–86 bp), and harlequin (81–105 bp). Somatic contractions of the oligo(dT) were observed in 43% of standard and 51% of harlequin merle dogs. A small proportion (4.6%) of the study cohort inherited de novo contractions or expansions of the Merle allele that resulted in dilute or harlequin coat patterns, respectively. CONCLUSIONS: The phenotypic consequence of the Merle SINE insertion directly depends upon oligo(dT) length. In transcription, we propose that the use of an alternative splice site increases with oligo(dT) length, resulting in insufficient PMEL and a pigment dilution spectrum, from dark grey to complete hypopigmentation. We further propose that during replication, contractions and expansions increase in frequency with oligo(dT) length, causing coat variegation (somatic events in melanocytes) and the spontaneous appearance of varieties of the merle phenotype (germline events). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13100-018-0131-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6091007 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60910072018-08-17 Length variations within the Merle retrotransposon of canine PMEL: correlating genotype with phenotype Murphy, Sarah C. Evans, Jacquelyn M. Tsai, Kate L. Clark, Leigh Anne Mob DNA Research BACKGROUND: The antisense insertion of a canine short interspersed element (SINEC_Cf) in the pigmentation gene PMEL (or SILV) causes a coat pattern phenotype in dogs termed merle. Merle is a semi-dominant trait characterized by patches of full pigmentation on a diluted background. The oligo(dT) tract of the Merle retrotransposon is long and uninterrupted and is prone to dramatic truncation. Phenotypically wild-type individuals carrying shorter oligo(dT) lengths of the Merle allele have been previously described and termed cryptic merles. Two additional coat patterns, dilute merle (uniform, steely-grey coat) and harlequin merle (white background with black patches), also appear in breeds segregating the Merle allele. RESULTS: Sequencing of all PMEL exons in a dilute and a harlequin merle reveals that variation exists solely within the oligo(dT) tract of the SINEC_Cf insertion. In fragment analyses from 259 dogs heterozygous for Merle, we observed a spectrum of oligo(dT) lengths spanning 25 to 105 base pairs (bp), with ranges that correspond to the four varieties of the merle phenotype: cryptic (25–55 bp), dilute (66–74 bp), standard (78–86 bp), and harlequin (81–105 bp). Somatic contractions of the oligo(dT) were observed in 43% of standard and 51% of harlequin merle dogs. A small proportion (4.6%) of the study cohort inherited de novo contractions or expansions of the Merle allele that resulted in dilute or harlequin coat patterns, respectively. CONCLUSIONS: The phenotypic consequence of the Merle SINE insertion directly depends upon oligo(dT) length. In transcription, we propose that the use of an alternative splice site increases with oligo(dT) length, resulting in insufficient PMEL and a pigment dilution spectrum, from dark grey to complete hypopigmentation. We further propose that during replication, contractions and expansions increase in frequency with oligo(dT) length, causing coat variegation (somatic events in melanocytes) and the spontaneous appearance of varieties of the merle phenotype (germline events). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13100-018-0131-6) contains supplementary material, which is available to authorized users. BioMed Central 2018-08-03 /pmc/articles/PMC6091007/ /pubmed/30123327 http://dx.doi.org/10.1186/s13100-018-0131-6 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Murphy, Sarah C. Evans, Jacquelyn M. Tsai, Kate L. Clark, Leigh Anne Length variations within the Merle retrotransposon of canine PMEL: correlating genotype with phenotype |
title | Length variations within the Merle retrotransposon of canine PMEL: correlating genotype with phenotype |
title_full | Length variations within the Merle retrotransposon of canine PMEL: correlating genotype with phenotype |
title_fullStr | Length variations within the Merle retrotransposon of canine PMEL: correlating genotype with phenotype |
title_full_unstemmed | Length variations within the Merle retrotransposon of canine PMEL: correlating genotype with phenotype |
title_short | Length variations within the Merle retrotransposon of canine PMEL: correlating genotype with phenotype |
title_sort | length variations within the merle retrotransposon of canine pmel: correlating genotype with phenotype |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091007/ https://www.ncbi.nlm.nih.gov/pubmed/30123327 http://dx.doi.org/10.1186/s13100-018-0131-6 |
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