A single affected male dog carrying an autosomal dominant allele for RCND sired five litters of pups with five unique and unaffected females. Affected dogs are shown in black, and unaffected dogs in white. Squares indicate males, circles females, and lines relationships. The portion of canine chromosome 5q14 showing linkage is indicated as a rectangle below each square or circle. Black bars indicate the portion of the affected parental chromosome inherited by each offspring from the affected father, and white bars indicate the portion inherited from the normal chromosome of the father. Alleles for each marker are indicated as numbers. Breakpoints allow the disease gene to be localized to a region adjacent to marker ZuBeCa6. Reprinted from Jónasdóttir et al.,³⁰ with the permission of the publisher.

The mutation causing a hypothetical disease is indicated by a yellow star. The various breeds with the disease are shown on the left; the chromosome responsible for the disease is indicated by a horizontal bar. Within each breed, meiotic breakpoints are indicated by the start and finish of the blue bar for each breed. When all breeds are considered together, the minimal associated region where the mutation must lie is between the red vertical lines.

Breeds vary according to many traits, including size, leg length, pelage (coat), color, and skull shape. Shown are borzoi (Panel A), basset hound (Panel B), Chihuahua (Panel C), giant schnauzer (Panel D), bichon frise (Panel E), collie (Panel F), French bulldog (Panel G), dachshund (Panel H), German shorthaired pointer (Panel I), papillon (Panel J), and Neapolitan mastiff (Panel K). (Images courtesy of Mary Bloom, American Kennel Club.)

On average, 10 to 12 dogs were genotyped for each of approximately 80 breeds. Trees were constructed with the use of data from each genotyped dog individually or by grouping the data from each member of a breed together, so each breed is represented as a single data entry. Data were also analyzed in two ways: by considering adjacent 10 single-nucleotide-polymorphism (SNP) windows or haplotypes or by considering each SNP alone. The two analytic methods provided similar results. Panel A shows the relationships among the various dog breeds. The color groupings indicate breeds that probably share common founders. Panel B shows the historical relationship of the breeds with the same color coding used in Panel A. In each case, breeds that share either common behaviors or morphologic traits are grouped together on the basis of DNA analysis, indicating that they probably share common ancestors. A black dot indicates at least 95% bootstrap support (a measure of the likelihood that an evolutionary split occurred in a given location in an evolutionary tree) after the performance of 1000 replicates. Reprinted from vonHoldt et al.²³ with permission of the publisher.

Panel A shows examples of breeds that are associated with chondrodysplasia, including the corgi, basset hound, and wire-haired dachshund. Panel B shows observed heterozygosity for breeds that are at increased risk for chondrodysplasia (red) and those that are not at increased risk (black) within the associated 34-kb region on canine chromosome 18. The x axis indicates the chromosomal position of association, and the y axis indicates observed heterozygosity The red and black lines indicate trends and highlight a 24-kb region with low heterozygosity in the dogs at risk for chondrodysplasia that is absent in dogs that are not at increased risk. Gene 1 is a pseudogene, a defective segment of DNA that resembles a gene but cannot be transcribed, called txndc1 (similar to the gene encoding thioredoxin-related transmembrane protein 1), and gene 2 marks the 33 end of the gene encoding semaphorin 3C (SEMA3C). The green boxes are conserved in both sequence and context in all mammals for which data are available. A 5-kb insertion (red rectangle), which was observed only in dogs with an association with chondrodysplasia and was found between the two putative regulatory elements, contains an fg f4 retrogene. LINE denotes long interspersed nuclear element, and SINE short interspersed nuclear element. Panel C shows expression studies indicating that the fg f4 retrogene is expressed in articular cartilage from the distal and proximal humerus isolated from a 4-week-old dog with chondrodysplasia. The retrogene and source gene are distinguished by a single-nucleotide polymorphism, which is cut by restriction enzyme BsrB1 in complementary DNA (cDNA) produced from the source gene, resulting in two bands on a 2% agarose gel, but uncut in the cDNA from the retrogene that is present in dogs with chondrodysplasia, resulting in only one band. MW denotes molecular weight marker. The source of control material is DNA isolated from the testes of a dog with chondrodysplasia. Modified from Parker et al.,⁵¹ with the permission of the publisher.