OMIA:001547-9031 : Wingless-2 in Gallus gallus (chicken)
Categories: Limbs / fins / digit / tail phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive lethal
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2019
Species-specific symbol: wg-2
History: Webb et al. (2018): "The wingless-2 (wg-2) mutation was originally identified at the University of Connecticut in a flock of chickens synthesized from Rhode Island Red, White Leghorn, Dorking breeds, and Red Jungle Fowl (Zwilling, 1956) . . . Wg-2 was the second wingless mutation characterized in the chicken; the first, now extinct, exhibited a similar phenotype and additionally was described as having incomplete or absent lungs, air sacs, and kidneys (Waters and Bywaters, 1943)" [see OMIA 001073-9031 for details of the original wingless mutant].
Webb et al. (2018) also reported that "In the late 1980s at the University of California Davis (UCD), a congenic inbred line was established by introgression of wg-2 in order to advance mapping and gene analysis research at a time wherein genomic tools were barely envisioned, much less the advent of the chicken sequencing project to advance poultry and vertebrate biology. The Wingless-2.331 (Wg-2.331) congenic inbred line was derived by first crossing known wg-2 carriers (+/wg-2) into the UCD 331.003 congenic line (Abplanalp et al., 1992; Pisenti et al., 1999). The +/wg-2 carrier progeny were confirmed by test-mating and then used to backcross to the parent line UCD 331.003. The backcross method using confirmed carrier (+/wg-2) progeny was repeated for at least 7 generations, with 2 additional backcrosses after the line was closed to improve fertility and viability, as per available breeding records and personal communications. This labor-intensive multi-year strategy placed the wg-2 locus in a uniform genetic background (99+% inbred) such that only the introgressed region containing the mutation along with other normal polymorphisms differs between normal (+/+ or +/wg-2) and mutant (wg-2/wg-2) individuals. The line was closed (inter se matings only) and perpetuated using +/wg-2 parents as breeders after being verified by test crosses. Over more than 60 yr of breeding, Mendelian ratios fit an autosomal recessive pattern of inheritance for the wg-2 mutation."
Inheritance: Citing Somes (1990) and Pisenti (1995), Webb et al. (2018) stated that the wg-2 "mutation is inherited in an autosomal recessive pattern and is an embryonic lethal".
Mapping: Webb et al. (2018) mapped this disorder "to a 227 kb candidate region on chicken chromosome 12".
Molecular basis: By sequencing the positional candidate region on chromosome GGA12 identified by Webb et al. (2018), in chickens from the powerful congenic line described in the History section above, Youngworth and Delany (2019) identified a likely causal variant as "a cytosine to thymine transition, resulting in a predicted stop codon in the transcript for RAF1 in wg-2/wg-2 individuals".
Clinical features: Youngworth and Delany (2019): "The phenotype of affected homozygous mutants is characterized by absent forelimbs, truncated hindlimbs, craniofacial malformations such as clefting or cross beak, and kidney and severe skin/feather malformations".
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|RAF1||Raf-1 proto-oncogene, serine/threonine kinase||Gallus gallus||12||NC_052543.1 (5204860..5135889)||RAF1||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1123||Wingless-2||RAF1||nonsense (stop-gain)||Naturally occurring variant||GRCg6a||12||g.5374854G>A||c.175C>T||p.(R59*)||NC_006099.5:g.5374854G>A ENSGALT00000033956.3:c.175C>T ENSGALP00000033314.3:p.Arg59Ter||rs314452077||rs314452077||2019||31075853|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2019||Youngworth, I., Delany, M.E. :|
|A premature stop codon in RAF1 is the priority candidate causative mutation of the inherited chicken Wingless-2 developmental syndrome. Genes (Basel) 10:353, 2019. Pubmed reference: 31075853 . DOI: 10.3390/genes10050353.|
|2018||Webb, A.E., Youngworth, I.A., Kaya, M., Gitter, C.L., O'Hare, E.A., May, B., Cheng, H.H., Delany, M.E. :|
|Narrowing the wingless-2 mutation to a 227 kb candidate region on chicken chromosome 12. Poult Sci 97:1872-1880, 2018. Pubmed reference: 29562287 . DOI: 10.3382/ps/pey073.|
|2012||Robb, E.A., Delany, M.E. :|
|Case study of sequence capture enrichment technology: identification of variation underpinning developmental syndromes in an amniote model. Genes (Basel) 3:233-47, 2012. Pubmed reference: 24704915 . DOI: 10.3390/genes3020233.|
|1999||Pisenti, J.M., Delany, M.E., Taylor, R.L., Abbott, U.K., Abplanalp, H., Arthur, J.A., Bakst, M.R., Baxter-Jones, C., Bitgood, J.J., Bradley, F.A., Cheng, K.M., Dietert, R.R., Dodgson, J.B., Donoghue, A.M., Emsley, A.B., Etches, R.J., Frahm, R.R., Gerrits, R.J., Goetinck, P.F., Grunder, A.A., Harry, D.E., Lamont, S.J., Martin, G.R., McGuire, P.E., Moberg, G.P., Pierro, L.J., Qualset, C.O., Qureshi, M.A., Shultz, F.T., Wilson, B.W. :|
|Avian genetic resources at risk: An assessment and proposal for conservation of genetic stocks in the USA and Canada. GRCP Report No. 20. Univ. California Division of Agriculture and Natural Resources, Genetic Resources Conservation Program, Davis CA. http://grcp.ucdavis.edu/publications/index.htm. :, 1999.|
|1996||Dealy, C.N., Kosher, R.A. :|
|Igf-i, insulin and fgfs induce outgrowth of the limb buds of amelic mutant chick embryos Development 122:1323-1330, 1996. Pubmed reference: 8620859 .|
|1995||Pisenti, J.M. :|
|Genetic and Environmental Influences on the Expression of the Mutation wingless-2 in the Chick Embryo. Ph.D. Thesis, University California, Davis, CA, USA :, 1995.|
|1992||Abplanalp, H., Sato, K., Napolitano, D., Reid, J. :|
|Reproductive performance of inbred congenic Leghorns carrying different haplotypes for the major histocompatibility complex. Poult Sci 71:9-17, 1992. Pubmed reference: 1539027 . DOI: 10.3382/ps.0710009.|
|1990||Somes, R.G. Jr :|
|Lethal mutant traits in chickens. In "Poultry Breeding and Genetics" (ed. R.D. Crawford), Elsevier, Amsterdam; Chapter 11 :293-315, 1990.|
|1956||Zwilling, E. :|
|Interaction between limb bud ectoderm and mesoderm in the chick embryo. IV. experiments with a wingless mutant. Journal of Experimental Zoology 132:241-251, 1956.|
|1943||Waters, N.F., Bywaters, J.H. :|
|Lethal embryonic wing mutation in the domestic fowl. Journal of Heredity 34:213-217, 1943.|
- Created by Frank Nicholas on 26 Feb 2011
- Changed by Frank Nicholas on 24 Sep 2019