Teaching an old dog new tricks: SINEs of canine genomic diversity

With >400 recognized breeds worldwide and a recently completed draft genomic sequence, the dog has emerged as a model organism of choice for the genetic dissection of morphological traits and diseases (1–3). Of great interest is the fact that a number of disorders in purebred dogs are also of human medical relevance (1, 2). In this context, the study by Clark et al. (4) in this issue of PNAS is exciting because of its implications on morphological, medical, and evolutionary grounds. Indeed, the authors have discovered a mutation in the dog SILV gene that is responsible for merle, a color patterning in the coat of various canine breeds. Strikingly, merle dogs exhibit auditory and ophthalmologic abnormalities similar to those observed for the human auditory-pigmentation disorder Waardenburg syndrome, which accounts for 2–5% of all human cases of congenital deafness (5).

The different dog breeds were established within the past few centuries from small numbers of founding individuals. As a consequence, linkage disequilibrium within the genome extends over at least 50-fold greater distances in dogs as compared to humans (3). Taking advantage of this feature of the dog genome, Clark et al. (4) carried out a whole-genome scan using the Shetland Sheepdog and were able to map the merle locus to the dog homologue of human chromosome 12q13. Characterization of the pigment gene SILV (6) located in this region revealed the presence of a short interspersed element (SINE) inserted at an intron/exon boundary that segregates with the merle phenotype (4). SINEs are “jumping genes” belonging to the retrotransposon class of mobile elements that propagate in their host genomes via a “copy and paste” mechanism (7–11). Because only a small fraction of mammalian genomes is functional, most retrotransposon insertions occur in genomic regions where they essentially induce …