Breaking news

COAT COLOR RESEARCH UPDATE:

HARLEQUIN GENE DISCOVERED!

Dr. Leigh Anne Clark and colleagues at Clemson University have recently discovered the gene that causes the Harlequin phenotype & publication is pending. The discovery is a most interesting one, as it turns out the harlequin gene isn't a "color" (pigment producing) gene at all. The harlequin gene simply alters the affect of the merle gene, so that the diluted regions (of merle coloration) otherwise seen are largely removed from the coat pattern, leaving behind the bi-color dog we know as a Harlequin.

So there is now proof positive that all Harlequins are genetic merles. The old notion of a "modifier gene" is still basically correct & helps the layman understand the interaction of harl and merle alleles: the "harl gene" acts on dogs with the merle mutation to produce a novel phenotype by "taking the grey out" (i.e. removing most all of the diluted pigment we call merle). Harlequins essentially are a "dominant modification" of normal (Mm) merle, in that the Harlequin gene acts on the merle gene to produce the Harlequin coat pattern, so the Harlequin Great Dane, in Neil O'Sullivan's eloquent phrase is a "dual heterozygote (HhMm)."

The merle mutation is a "dominant" mutation of a pigment gene known as SILV that produces a protein called PMEL17. Merle is a semi-dominant, meaning this one gene with only two alleles produces three distinct phenotypes: non-merle, normal merle (the heterozygote) and white merle (the homozygote which is commonly defective & referred to in Danes as a merlikin). The merle gene produces a characteristic increase in white areas & in areas of reduced pigment, with patches of mid-tone and full pigment in the heterozygote typically, with the homozygote usually being mostly white. No merle ever inherits a copy of the harl gene.

The harl mutation is also a "dominant" mutation where the "wild type" allele does not reduce pigmentation. The harl mutation acts as a modifier on merle dogs, further reducing the amount of pigment seen in the coat. Dogs without a merle gene can carry the harl gene sight unseen. Both Harlequin and Merle Great Dane have black pigment left behind because every normal Merle & normal Harlequin have one copy of the "wild type" gene for both merle and harl genes. A dog with two copies of the merle mutation AND one copy of the harl mutation appears mostly white with some black & some merle patches possible in a pattern referred to as "white." (Any embyo that receives two copies of the harl gene is apparently resorbed.)

An important take home message of this recent research which parallels breeder knowledge accumulated over many decades is that all Harlequin and Merle Great Danes are unique; like snowflakes no two are ever exactly alike. This is because of the unique nature of the merle gene: for all that all Harlequins & Merles inherit the same merle mutation, the affect will vary in every individual dog. The coat pattern therefore cannot be controlled as to the details of pigment distribution (i.e. specific patterning will necessarily vary).

How this effect is exactly achieved is currently being explored by Dr. Clark's laboratory. Her earlier work included the discovery of the merle gene, as well as the isolation of the harlequin gene to chromosome 9 (see PDF & other links below). The GDCA's Charitable Trust underwrote the advent of this research through "The Harlequin Gene Project" and the Board of Directors has recently voted to again devote funding to Dr. Clark's continuing exploration of the harlequin gene & its interaction with merle and other genes in the Great Dane. We thank Dr. Clark for her continuing interest in our breed.

The above is a layman's explanation of the genes producing the Harlequin and Merle phenotypes.

For a more detailed explanation, see the following links:

Standard Coat Color Genetics For Breeders: http://www.chromadane.com/standardcoat.htm

Coat Color Alleles in Dogs: http://homepage.usask.ca/~schmutz/dogcolors.html 

Recommended Reading:

Genes Affecting Coat Color In Domestic Dogs: a Review: http://www.ncbi.nlm.nih.gov/pubmed/18052939

Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog: http://www.pnas.org/cgi/content/abstract/0506940103v1

Genome-wide linkage scan localizes the harlequin locus in the Great Dane to chromosome 9
http://www.ncbi.nlm.nih.gov/pubmed/18513894

Merle PDF File

Harl1 PDF FILE


Submitted by JP Yousha, Chair, H&R Committee, GDCA 2009
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