Monday, October 01, 2007

The gene-mapper’s best friend

Genetic variants associated with dominant or recessive disease-related traits in dogs can be mapped efficiently and with high confidence, report two studies to be published online this week in Nature Genetics. As dogs and humans have a similar complement of genes, the mapping of disease-associated variants in dogs may make an important contribution to the study of human genetic disease.

There are more than 400 genetically distinct dog breeds. As each breed originated in a small number of founder dogs, there is a limited amount of genetic diversity within each breed. This sort of genome structure is ideal for the rough mapping of genes because it allows one to analyze most of the genome with a limited number of genetic markers. Kerstin Lindblad-Toh and colleagues found small regions of the genome to be associated with two traits by assessing a relatively small number of single-nucleotide polymorphisms (27,000) in only 20 dogs.

The authors identified a genomic region containing only one gene—MITF—as responsible for the absence of skin and coat pigmentation in white boxers, which also predisposes them to deafness. They also identified a region associated with the dorsal hair ridge in Ridgeback dogs, which are prone to dermoid sinus, a neural tube defect. In the accompanying paper, Leif Andersson and colleagues carried out fine mapping of the region associated with the Ridgeback hair ridge, and showed that the causative mutation is a duplication containing four different genes—FGF3, FGF4, FGF19 and ORAOV1.

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