Serial translocation by means of circular intermediates underlies colour sidedness in cattle.
Durkin, Keith ; Coppieters, Wouter ; et al
in Nature (2012), 482(7383), 81-4
Colour sidedness is a dominantly inherited phenotype of cattle characterized by the polarization of pigmented sectors on the flanks, snout and ear tips. It is also referred to as 'lineback' or 'witrik ... [more ▼]
Colour sidedness is a dominantly inherited phenotype of cattle characterized by the polarization of pigmented sectors on the flanks, snout and ear tips. It is also referred to as 'lineback' or 'witrik' (which means white back), as colour-sided animals typically display a white band along their spine. Colour sidedness is documented at least since the Middle Ages and is presently segregating in several cattle breeds around the globe, including in Belgian blue and brown Swiss. Here we report that colour sidedness is determined by a first allele on chromosome 29 (Cs(29)), which results from the translocation of a 492-kilobase chromosome 6 segment encompassing KIT to chromosome 29, and a second allele on chromosome 6 (Cs(6)), derived from the first by repatriation of fused 575-kilobase chromosome 6 and 29 sequences to the KIT locus. We provide evidence that both translocation events involved circular intermediates. This is the first example, to our knowledge, of a phenotype determined by homologous yet non-syntenic alleles that result from a novel copy-number-variant-generating mechanism. [less ▲]Detailed reference viewed: 96 (58 ULg)
Molecular dissection of the color-sided pehnotype in cattle reveals a novel mechanism of chromosome evolution involving circular shuttling intermediates.
Durkin, Keith ; Cambisano, Nadine ; Ahariz, Naïma et al
Poster (2011, May)Detailed reference viewed: 32 (15 ULg)
Molecular dissection of the color-sided phenotype in cattle reveals a novel mechanism of chromosome evolution involving circular shuttling intermediates.
Durkin, Keith ; Cambisano, Nadine ; Ahariz, Naïma et al
in Chromosome Research : An International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology (2011, May), 19(S1), 18
The color-sided (Cs) phenotype is a dominant coat color pattern segregating in several breeds including Belgian Blue Cattle (BBC) and Brown Swiss (BS). A genome-wide association study performed in BBC ... [more ▼]
The color-sided (Cs) phenotype is a dominant coat color pattern segregating in several breeds including Belgian Blue Cattle (BBC) and Brown Swiss (BS). A genome-wide association study performed in BBC unambiguously positioned the Cs locus on chromo- some 29 (BTA29); however, SNP arrays and CGH detected an equally perfectly associated <480 kb duplication encompassing the KIT gene on chromo- some 6 (BTA6). FISH analysis reconciled these results by revealing an intrachromosomal duplication, which transposed a fragment of BTA6 to BTA29. The organization of the duplicated segment, including breakpoint definition, was determined by high-throughput resequencing and revealed that the transpo- sition occurred via a circular intermediate. The trans- posed KIT copy was shown to be transcriptionally competent, suggesting that dominant color-sidedness results from dysregulated expression of KIT. Similar analyses of the color-sided phenotype conducted in BS revealed linkage on BTA6, a <120- kb-BTA6 duplication (which overlaps with the BBC duplication), and a <414-kb-BTA29 duplication adja- cent to the BTA29 breakpoint defined in BBC. FISH analysis showed the duplicated portion of BTA29 was located on BTA6 and adjacent to the KIT gene. SNP genotyping indicated that the BTA6 and BTA29 haplotypes associated with color-sidedness in BS and BBC were near identical, demonstrating the non-independence of the two chromosomal events. High-throughput resequencing of a color-sided BS animal defined the corresponding breakpoints and suggests that the BS Cs allele is derived from the BBC duplication [less ▲]Detailed reference viewed: 51 (17 ULg)
LUPA: a European initiative taking advantage of the canine genome architecture for unravelling complex disorders in both human and dogs.
Lequarré, Anne-Sophie ; ; et al
in Veterinary Journal (2011), 189(2), 155-9
The domestic dog offers a unique opportunity to explore the genetic basis of disease, morphology and behaviour. Humans share many diseases with our canine companions, making dogs an ideal model organism ... [more ▼]
The domestic dog offers a unique opportunity to explore the genetic basis of disease, morphology and behaviour. Humans share many diseases with our canine companions, making dogs an ideal model organism for comparative disease genetics. Using newly developed resources, genome-wide association studies in dog breeds are proving to be exceptionally powerful. Towards this aim, veterinarians and geneticists from 12 European countries are collaborating to collect and analyse the DNA from large cohorts of dogs suffering from a range of carefully defined diseases of relevance to human health. This project, named LUPA, has already delivered considerable results. The consortium has collaborated to develop a new high density single nucleotide polymorphism (SNP) array. Mutations for four monogenic diseases have been identified and the information has been utilised to find mutations in human patients. Several complex diseases have been mapped and fine mapping is underway. These findings should ultimately lead to a better understanding of the molecular mechanisms underlying complex diseases in both humans and their best friend. [less ▲]Detailed reference viewed: 27 (4 ULg)