Dataset Information

Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog.

ABSTRACT: Merle is a pattern of coloring observed in the coat of the domestic dog and is characterized by patches of diluted pigment. This trait is inherited in an autosomal, incompletely dominant fashion. Dogs heterozygous or homozygous for the merle locus exhibit a wide range of auditory and ophthalmologic abnormalities, which are similar to those observed for the human auditory-pigmentation disorder Waardenburg syndrome. Mutations in at least five genes have been identified as causative for Waardenburg syndrome; however, the genetic bases for all cases have not been determined. Linkage disequilibrium was identified for a microsatellite marker with the merle phenotype in the Shetland Sheepdog. The marker is located in a region of CFA10 that exhibits conservation of synteny with HSA12q13. This region of the human genome contains SILV, a gene important in mammalian pigmentation. Therefore, this gene was evaluated as a candidate for merle patterning. A short interspersed element insertion at the boundary of intron 10/exon 11 was found, and this insertion segregates with the merle phenotype in multiple breeds. Another finding was deletions within the oligo(dA)-rich tail of the short interspersed element. Such deletions permit normal pigmentation. These data show that SILV is responsible for merle patterning and is associated with impaired function of the auditory and ophthalmologic systems. Although the mutant phenotype of SILV in the human is unknown, these results make it an intriguing candidate gene for human auditory-pigmentation disorders.

SUBMITTER: Clark LA

PROVIDER: S-EPMC1360527 | biostudies-literature | 2006 Jan

REPOSITORIES: biostudies-literature

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Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog.

Clark Leigh Anne LA Wahl Jacquelyn M JM Rees Christine A CA Murphy Keith E KE

Proceedings of the National Academy of Sciences of the United States of America 20060109 5

Merle is a pattern of coloring observed in the coat of the domestic dog and is characterized by patches of diluted pigment. This trait is inherited in an autosomal, incompletely dominant fashion. Dogs heterozygous or homozygous for the merle locus exhibit a wide range of auditory and ophthalmologic abnormalities, which are similar to those observed for the human auditory-pigmentation disorder Waardenburg syndrome. Mutations in at least five genes have been identified as causative for Waardenburg ...[more]

PMID: 16407134

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Project description: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.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.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).

Project description:The domestic dog shows a wide range of morphologies, that humans have selected for in the process of creating unique breeds. Recent studies have revealed correlations between changes in morphology and behaviour as reported by owners. For example, as height and weight decrease, many undesirable behaviours (non-social fear, hyperactivity and attention seeking) become more apparent. The current study aimed to explore more of these correlations, but this time used reports from trained observers. Phenotypic measurements were recorded from a range of common dog breeds (n = 45) and included cephalic index (CI: the ratio of skull width to skull length), bodyweight, height and sex. These data were then correlated with results from the Dog Mentality Assessment (DMA), which involves trained observers scoring a dog's reaction to stimuli presented over 10 standardised subtests. Each subtest is designed to evoke a behavioural response. Backward elimination and weighted step-wise regression revealed that shorter dogs demonstrated more aggressive tendencies, reacting defensively toward both assistants dressed as ghosts (p = 0.045), and to a dummy (p = 0.008). Taller dogs were more affectionate when greeting and being handled by humans (p = 0.007, p = <0.001, respectively). Taller dogs were also more cooperative (p = <0.001), and playful (p = 0.001) with humans than shorter dogs. Heavier dogs were more inquisitive toward a dummy (p = 0.011), to the source of a metallic noise (p = 0.010) and to an assistant (p = 0.003). Heavier dogs were also more attentive to the ghosts (p = 0.013). In comparison, lighter dogs were cautious of a dummy (p = <0.001) and fearful of the sound of a gunshot (p = <0.001). Lighter dogs were also cautious of, and demonstrated prolonged fearfulness toward, the source of metallic noise (p = <0.001, p = <0.034, respectively). With a far larger sample and the advantage of third-party reporting (which overcomes potential owner bias), the current findings build on previous studies in this field, further supporting covariance between morphology and behaviour.

Dataset Information

Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog.

Publications

Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog.

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