George M. Strain, PhD
Recent issues of Top Notch Toys have printed dialog about the merle gene, especially relating to its presence in the Chihuahua breed. One particular article (1) cited research of mine (2) with an incorrect interpretation that I wish to correct. In addition, I would like to provide unbiased up-to-date information on the merle gene that may inform and clarify the debate on this issue. I have been performing research on hearing and deafness since the late 1980’s, and am identified as a leading authority on deafness in dogs, so I am well positioned to provide this information. I should point out that publications and writings of mine from past years discussing the merle gene no longer represent my opinion, as recent research has led me to change my position.
The above cited article contained the statement that According to Dr. George Strain merle and piebald dogs with blue eyes are 50% more likely to be deaf.@ The research from which this was drawn only applied to the piebald gene and only applied to the Dalmatian breed, where blue eyes and deafness are a wide-spread problem (30% of US Dalmatians are deaf in one or both ears). My research did not apply to dogs with merle, and I am unaware of any study examining this issue using adequate numbers of dogs and dogs from breeds other than Dachshund, where the published studies have limitations (see below).
Two pigment genes are associated with deafness in dogs: piebald (s) and merle (M). Piebald, which is present in Dalmatians, bull terriers, cocker spaniels, Jack Russell terriers, Chihuahuas and others, is a recessive gene. There are three recessive alleles for piebald: Irish spotting (si), piebald (sp), and extreme white piebald (sw); dogs that have uniform color without white carry the dominant allele (S). The piebald gene produces areas of white by suppressing pigmentation cells (melanocytes). Merle, which is present in Shetland sheepdogs, Australian shepherds, Dachshunds, Great Danes and others, is a dominant gene. Merle produces a color pattern where patches of color are diluted or absent (white); animals homozygous with the recessive allele (mm) have solid color. Dogs with piebald must be homozygous to have areas of white, while merles can be either heterozygous (mM) or homozygous (MM). There is no evidence to suggest that dogs carrying both the piebald and merle genes have an increased likelihood of deafness.
Much of the literature on merle in the past focused on problems seen in homozygous merles and in breeds where the merle gene can produce dramatic effects B in some cases including deafness, blindness and microphthalmia, and sterility. Even heterozygous dogs in these breeds can have less serious visual and auditory deficits. This indeed happens with some breeds, but unfortunately many people have taken this truth and extrapolated it to apply to all breeds carrying the merle gene, which is not true. For example, dogs in the Catahoula breed can be homozygous merle without any of these health defects, and heterozygotes do not seem to be affected. Until recently it was not possible to even distinguish between mM and MM merles in some breeds.
Since not all breeds carrying the merle gene experience the deleterious effects, it is incautious to proclaim that the presence of this pattern in a breed will be injurious to the breed without first investigating whether deaf or blind dogs result from breeding heterozygous merles. Are there any known deaf or blind merle chihuahuas? If so, are they heterozygous or homozygous? In many breeds carrying merle, breeders know not to breed homozygous merles, and visual and auditory deficits do not seem to be a problem in the heterozygotes. Studies have examined auditory function (3) and visual function (4) in heterozygous and homozygous dappled (merle) Dachshunds, as described in several writings by Dr. Malcolm Willis. These studies, from geographically and numerically restricted populations, found hearing loss and deafness and visual abnormalities, but only examined small numbers of dogs B 38 in the first study and 18 in the second. Dappled Dachshunds, when carefully bred to avoid MM, do not appear to have deafness or blindness in the general population, so one must be careful to not raise alarms at the presence of merle in a breed until experience shows that a true problem exists.
A large leap in understanding merle occurred when Clark and Murphy of Texas A&M University identified and sequenced the canine gene for merle in 2006 (5). The gene, named SILV, (also known as Silver in mice) plays a role in pigmentation in skin, eye, and ear. Dogs with the merle phenotype have a short piece of DNA inserted into this gene B a DNA modification known as a short interspersed element (SINE). This work was performed with Shetland sheepdogs, then confirmed in merles from eleven other breeds, including chihuahua. The sequence of the SINE was the same in all breeds, suggesting that all breeds in the study shared a common ancestor. The merle SINE insertion has three components: a head, a body and a tail; the latter contains a long string of repeated adenine nucleotides (polyA). For a dog to show the merle phenotype, it must have both the SINE insertion and a polyA tail that is of sufficient length (90-100 adenine repeats). Some merle-merle breedings produce homozygous merles called cryptic because they don=t show the merle phenotype, and when bred they do not produce any merle offspring. It turns out that the polyA tail in cryptic merles has been truncated to 65 or fewer adenine repeats. So, the merle gene phenotype can revert to the non-merle in one generation. In the same way, it is theoretically possible for the polyA tail length to increase from genetic processing error, spontaneously producing a merle (5,6). The likelihood of this possibility is unknown but probably low.
It has been suggested that merle appeared in the Chihuahua breed from a cross to another breed, such as the Dachshund. Others have suggested that the gene has been present for many generations, but that the pigmentation pattern was incorrectly described, such as blue and tan or black and silver. A single event of the first possibility might still make it hard to explain all of the merle Chihuahuas now in existence. Regardless of the source of merle in the breed, to my knowledge there is no data at this time to suggest that merle Chihuahuas are prone to visual or auditory problems. I would encourage the breed organization investigate the prevalence of visual and auditory disorders in merle Chihuahuas prior to making decisions affecting the breed standard.
More information on deafness in general can be found on my research web page:
1. Lambert G. 2006. Chihuahuas – Any color (breed) marked or splashed?? Top Notch Toys 22(4):116.
2. Strain GM. 2004. Deafness prevalence and pigmentation and gender associations in dog breeds at risk. The Veterinary Journal 167(1):23-32.
3. Reetz, I., Stecker, M., & Wegner, W. 1977. Audiometrische Befunde in einer Merlezucht [Audiometric findings in dachshunds (merle gene carriers)]. Deutsche Tierärztliche Wochenschrift 84(7):273 277.
4. Klinckmann G, Koniszewski G, Wegner W. 1986. Light microscopic investigations on the retinae of dogs carrying the Merle factor. Journal of Veterinary Medicine A 33(9):674 688.
5. Clark LE et al. 2006. Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog. Proceedings of the National Academy of Sciences 103(5):1376 81.
6. Cordaux R, Batzer MA. 2006. Teaching an old dog new tricks: SINEs of canine genomic diversity. Proceedings of the National Academy of Sciences 103(5):1157 8.