Canine Genome mapping : Current Scenario

Introduction

Understanding the canine karyotype has proved to be one of the toughest problems as yet faced by geneticists. The karyotype of Canis familiaris, the pet dog is one of the most difficult mammalian karyotypes to work with. The mapping of the canine genome been hastened by the publication of radiation hybrid (RH), genetic linkage, and dog/human comparative maps.

Genome map
Breen et al at the Animal Health Trust, UK have recently described the first fully integrated, comprehensive map of the canine genome, incorporating detailed cytogenetic, radiation hybrid (RH), and meiotic information. The investigators have mapped a total of 266 chromosome-specific cosmid clones, each containing a microsatellite marker, to all 38 canine autosomes by fluorescence in situ hybridization (FISH).

In another study performed a year earlier, Sargan et al had reported the construction of a 1500-marker RH map, with 1078 microsatellites, 320 dog gene markers, and 102 chromosome-specific markers. In the karyotype map constructed, each chromosome can be identified by one meiotic linkage group and one or more RH groups. With more than a total of 1800 markers, the map included more than 90% of the entire dog genome.

Canine Minimal Screening Set 1
Richman et al at the Fred Hutchinson Cancer Research Centre, have characterized a subset of 172 microsatellite markers from the canine map, termed 'Minimal Screening Set 1' (Canine MSS-1), to be used for initial genome-wide genetic linkage studies. From the results of their studies, it appears that 42% of the genome is within 5 cM of at least one marker in the minimal screening set, while 77% of the genome is within 10 cM. According to the research team, this minimal mapping set provides an efficient and cost effective way to start screening pedigrees of interest for genetic linkage.

Micro rearrangements of evolutionarily conserved segments rare!
The dog has one of the most extensively rearranged mammalian karyotypes investigated so far. Parker et al at the Fred Hutchinson Cancer Research Centre have developed and positioned 52 new gene-associated polymorphic markers on the canine meiotic linkage map. Forty-eight of 52 genes map to a chromosomal region predicted to contain genes from the corresponding region of the human genome. According to Parker et al microrearrangements of evolutionarily conserved segments between the canine and human genomes are rare, and account for less than 0.5% of gene data reported to date.

Canine X-linked progressive retinal atrophy (XLPRA)
Canine X-linked progressive retinal atrophy (XLPRA) is a hereditary, progressive retinal degeneration mapped to the canine X chromosome in a region flanked by the dystrophin (DMD) and tissue inhibitor of metalloproteinase 1 (TIMP1) genes, and is tightly linked to the gene RPGR.

TGM 1 gene seqeunced
The transglutaminase 1 gene (TGM1) codes for an enzyme essential in cross-linking the structural proteins that form the cornified envelope, a vital component of the outermost layer of the skin, the stratum corneum. Credille et al at the department of veterinary pathology, Texas A&M University have mapped the canine TGM1gene and observed that it has 2,448 nucleotides distributed over 15 exons.

MSX2 gene for normal face and head growth and shape sequenced
The canine MSX2 gene encodes a homeodomain transcription factor essential for normal head and face morphogenesis. Haworth et al at the human biochemical genetics unit, University College, London have sequenced the MSX2 gene and localized it to dog chromosome 4q23. In their study, the investigators examined the DNA from 11 individual domestic dogs belonging to 10 different breeds. They observed that variation in MSX2 does not contribute to the diversity of face shape observed in these domestic dogs and that the MSX2 sequence is strongly conserved between different dog breeds.

Canine generalized progressive retinal atrophies (gPRA)
Lin et al at the department of veterinary medicine, National Taiwan University, Taiwan have been working on the canine generalized progressive retinal atrophies (gPRA), a group of degenerative retinal diseases that cause hereditary blindness in a significant number of dog breeds. Using the expressed sequence tag (EST) approach, the investigators have worked on identifying candidate genes from canine retinal cDNA libraries.

The gene for canine narcolepsy
Li et al at the Stanford Centre for Narcolepsy Research have been investigating the genes responsible for canine narcolepsy, a condition characterized by excessive daytime sleepiness. The investigators have successfully cloned the hypocretin receptor 2, and the gene for autosomal recessive canine narcolepsy, which is believed to be located in canine chromosome 12 (CFA12), in a region corresponding to human chromosome 6p12-q13.

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