Recent Clinical Advances on Hereditary Diseases and Breed Predispositions
World Small Animal Veterinary Association World Congress Proceedings, 2008
School of Veterinary Medicine, University of Pennsylvania
Philadelphia, PA, USA

The topic of clinical genetics in small animals has often been overlooked by veterinarians, presumably because hereditary disorders were thought to occur rarely in clinical practice, to offer relatively little for a clinician to do, or to represent an area where clinicians defer to breeders or academic institutions. However, many of the characteristic breed traits and common and rare genetic diseases and predispositions seen in veterinary practice are now recognized to have a heritable basis and have taken on an increasingly important role in veterinary medicine as many infectious diseases, nutritional deficiencies, and intoxications have been controlled. Today, many hereditary diseases are well characterized from clinical signs to the gene defect, precise diagnostic tools have been developed to detect affecteds but also carriers, specific treatments can be offered for a few, and genetic counseling with breeder clients can improve the health of small animals in future generations.

It is difficult for a clinician to keep up with the rapidly accumulating information on clinical genetics and the large spectrum of disorders and genetic predispositions. Thus, comprehensive update resources are needed. There are several web site that provide some information on many different diseases in companion animals such as 'Inherited Diseases in Dogs'(; Mendelian Inheritance in Animals,; Canine Inherited Disease Database; and the FAB list of feline hereditary disorders The WSAVA Committee on Hereditary Diseases, established in late 2006, is setting up a data base with the Veterinary Information Network ( with pertinent practical information on clinical features, genetic diagnostics, and management specifically for the clinician. This novel tool will be demonstrated and integrated into this 3-hour session. We will begin with the recent exciting advances on canine and feline genetics and the discovery and examples of the characterization of hereditary diseases and genetic breed predispositions to disease. The recent sequencing of the canine and feline genome and thereby generated tools really facilitated these investigations and permit soon an emphasis shift from single gene defects to complex traits. Thereafter we will be explaining the practical tools of genetic testing to reach a definitive diagnosis from routine clinical to molecular genetic tests for single gene disorders. Finally, guidelines on genetic counseling of breeders and pet owners by clinicians will be provided. While there are clear guidelines for single gene defects with accurate tests, the counseling is more challenging for less well defined disorders and complex traits. Case examples will illustrate the salient features during each presentation.

Genetic diseases are caused by chromosomal alterations or gene mutations. Disease-causing mutations are heritable changes in the sequence of genomic DNA that alter the expression, structure, and function of the coded protein. The genotype refers to the animal's genetic makeup, reflected by its DNA sequence, whereas the phenotype relates to the clinical manifestation of specific gene(s) and environment, or both. The molecular genetic defect is now known for 60 hereditary disorders in dogs and 20 in cats. These molecular genetic changes include point mutations, deletions, and insertions in the DNA sequence that result in a missense or nonsense sequence with an altered codon sequence. For approximately half of the disorders suspected to be of a genetic nature the mode of inheritance remains, however, unknown and may well be polygenic. The canine genome (7.5x) has been sequenced and annotated during the past years, which has greatly facilitated the characterization of molecular bases of simple and complex hereditary diseases in dogs, and will continue to do so. The high quality canine DNA genome sequence of a boxer makes up a total of ~20,000 genes. Similarly, the recently published low density (1.9x) feline genome sequence has identified 19,000 genes and facilitated the characterization of genetic diseases in cats. Based upon the vast variety of polymorphic markers (microsatellites and single nucleotide polymorphisms [SNPs]) spread throughout the genome, new genes can be discovered and associated with disease traits, while originally some were used for parentage testing. Moreover, certain SNP panels can be used to group breeds of dogs and cats and reveal their structure and ancestry. Recently, this technology has been applied to develop a mixed breed test (Mars Veterinary Wisdom Panel Mx mixed breed analysis based upon 130 AKC breeds or MetaMorphix Canine Heritage Breed Test based upon 38 breeds). Knowing the breed contributions of a mixed breed puppy may predict the size, temperament and other traits as well as possibly some hereditary disease predilections.

The dog has 76 autosomes (38 pairs) and 2 sex chromosomes (78XX or 78XY), and the cat's karyotype is 38XX or 38XY. The pattern of inheritance depends mainly on two factors:

1.  Whether the mutation is located on an autosome (autosomal) or on the X-chromosome (X-linked), and

2.  Whether the phenotype, the observable expression of a genotype as a disease trait, is dominant, i.e., expressed when only one chromosome of a pair carries the mutation, or recessive, i.e., expressed when both chromosomes of a pair carry the mutation.

Thus, it is the phenotype rather than the mutant gene or protein that is dominant or recessive. Whereas in humans more diseases are dominantly inherited, recessive traits are favored by the common inbreeding practices in small animals. In addition, complex genetic traits where more than one gene alteration (polygenic) and environmental factors play a role in the expression and severity of a disease are being recognized. Many susceptibilities to disease, such as inflammatory, immune-mediated, and neoplastic diseases as well as drug reactions, are considered to be transmitted by a complex trait.

Speaker Information
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School of Veterinary Medicine
University of Pennsylvania
Philadelphia, Pennsylvania, USA

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