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The Rose-comb Mutation in Chickens Constitutes a Structural Rearrangement Causing Both Altered Comb Morphology and Defective Sperm Motility
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
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2012 (English)In: PLOS Genetics, ISSN 1553-7404, Vol. 8, no 6, e1002775- p.Article in journal (Refereed) Published
Abstract [en]

Rose-comb, a classical monogenic trait of chickens, is characterized by a drastically altered comb morphology compared to the single-combed wild-type. Here we show that Rose-comb is caused by a 7.4 Mb inversion on chromosome 7 and that a second Rose-comb allele arose by unequal crossing over between a Rose-comb and wild-type chromosome. The comb phenotype is caused by the relocalization of the MNR2 homeodomain protein gene leading to transient ectopic expression of MNR2 during comb development. We also provide a molecular explanation for the first example of epistatic interaction reported by Bateson and Punnett 104 years ago, namely that walnut-comb is caused by the combined effects of the Rose-comb and Pea-comb alleles. Transient ectopic expression of MNR2 and SOX5 (causing the Pea-comb phenotype) occurs in the same population of mesenchymal cells and with at least partially overlapping expression in individual cells in the comb primordium. Rose-comb has pleiotropic effects, as homozygosity in males has been associated with poor sperm motility. We postulate that this is caused by the disruption of the CCDC108 gene located at one of the inversion breakpoints. CCDC108 is a poorly characterized protein, but it contains a MSP (major sperm protein) domain and is expressed in testis. The study illustrates several characteristic features of the genetic diversity present in domestic animals, including the evolution of alleles by two or more consecutive mutations and the fact that structural changes have contributed to fast phenotypic evolution.

Place, publisher, year, edition, pages
2012. Vol. 8, no 6, e1002775- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-178136DOI: 10.1371/journal.pgen.1002775ISI: 000305961000037OAI: diva2:542222
Available from: 2012-07-30 Created: 2012-07-30 Last updated: 2015-10-01Bibliographically approved
In thesis
1. Monogenic Traits Associated with Structural Variants in Chicken and Horse: Allelic and Phenotypic Diversity of Visually Appealing Traits
Open this publication in new window or tab >>Monogenic Traits Associated with Structural Variants in Chicken and Horse: Allelic and Phenotypic Diversity of Visually Appealing Traits
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Domestic animals have rich phenotypic diversity that can be explored to advance our understanding of the relationship between molecular genetics and phenotypic variation. Since the advent of second generation sequencing, it has become easier to identify structural variants and associate them with phenotypic outcomes. This thesis details studies on three such variants associated with monogenic traits.

The first studies on Rose-comb in the chicken were published over a century ago, seminally describing Mendelian inheritance and epistatic interaction in animals. Homozygosity for the otherwise dominant Rose-comb allele was later associated with reduced rooster fertility. We show that a 7.38 Mb inversion is causal for Rose-comb, and that two alleles exist for Rose-comb, R1 and R2. A novel genomic context for the gene MNR2 is causative for the comb phenotype, and the bisection of the gene CCDC108 is associated with fertility issues. The recombined R2 allele has intact CCDC108, and normal fertility.

The dominant phenotype Greying with Age in horses was previously associated with an intronic duplication in STX17. By utilising second generation sequencing we have examined the genomic region surrounding the duplication in detail, and excluded all other discovered variants as causative for Grey.

Dun is the ancestral coat colour of equids, where the individual is mostly pale in colour, but carries intensely pigmented primitive markings, most notably a dorsal stripe. Dun is a dominant trait, and yet most domestic horses are non-dun in colour and intensely pigmented. We show that Dun colour is established by radially asymmetric expression of the transcription factor TBX3 in hair follicles. This results in a microscopic spotting phenotype on the level of the individual hair, giving the impression of pigment dilution. Non-dun colour is caused by two different alleles, non-dun1 and non-dun2, both of which disrupt the TBX3-mediated regulation of pigmentation. Non-dun1 is associated with a SNP variant 5 kb downstream of TBX3, and non-dun2 with a 1.6 kb deletion that overlaps the non-dun1 SNP. Homozygotes for non-dun2 show a more intensely pigmented appearance than horses with one or two non-dun1 alleles. We have also shown by genotyping of ancient DNA that non-dun1 predates domestication.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 59 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1124
Structural variation, Pigmentation, Domestication, Equids, MNR2, CCDC108, STX17, TBX3, Grey, Dun, non-dun, Rose-comb, Chicken, Genetic mapping, Phenotyping
National Category
Genetics Genetics and Breeding
Research subject
Molecular Genetics
urn:nbn:se:uu:diva-259621 (URN)978-91-554-9295-3 (ISBN)
Public defence
2015-09-25, room B42, at the BMC, Husargatan 3, Uppsala, 13:15 (English)
Available from: 2015-09-04 Created: 2015-08-10 Last updated: 2015-10-01

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Imsland, FreyjaDorshorst, BenRubin, Carl-JohanHallböök, FinnAndersson, Leif
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