OMIA 000702-9031 : Nanomelia in Gallus gallus

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1994

Molecular basis: By cloning and sequencing a very likely candidate gene (based on prior physiological and biochemical studies, reinforced by strong linkage between the disorder and that gene), Primorac et al. (1994) demonstrated "A stop codon . . . at codon 1513, which is located in the eighth repeat of the chondroitin sulfate 2 domain of the large tenth exon [of the avian aggrecan gene]."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
ACAN aggrecan Gallus gallus 10 NC_006097.5 (13533614..13488503) ACAN Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Nanomelia ACAN nonsense (stop-gain) Galgal4 10 g.12554157G>T c.4537G>T p.E1513* 1994 7827752 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

References


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.
2003 Mosher, T.J., Chen, Q., Smith, M.B. :
1H magnetic resonance spectroscopy of nanomelic chicken cartilage: effect of aggrecan depletion on cartilage T2. Osteoarthritis Cartilage 11:709-15, 2003. Pubmed reference: 13129689.
2000 Velleman, S.G. :
The role of the extracellular matrix in skeletal development. Poult Sci 79:985-9, 2000. Pubmed reference: 10901199.
1999 Primorac, D., Johnson, C.V., Lawrence, J.B., McKinstry, M.B., Stover, M.L., Schanfield, M.S., Andelinovic, S., Tadic, T., Rowe, D.W. :
Premature termination codon in the aggrecan gene of nanomelia and its influence on mRNA transport and stability Croatian Medical Journal 40:528-532, 1999. Pubmed reference: 10554355.
1996 Domowicz, M., Krueger, R.C., Li, H., Mangoura, D., Vertel, B.M., Schwartz, N.B. :
The nanomelic mutation in the aggrecan gene is expressed in chick chondrocytes and neurons International Journal of Developmental Neuroscience 14:191-201, 1996. Pubmed reference: 8842798.
1995 Li, H., Schwartz, N.B. :
Gene structure of chick cartilage chondroitin sulfate proteoglycan (aggrecan) core protein Journal of Molecular Evolution 41:878-885, 1995. Pubmed reference: 8587132.
1994 Primorac, D., Stover, M.L., Clark, S.H., Rowe, D.W. :
Molecular basis of nanomelia, a heritable chondrodystrophy of chicken Matrix Biology 14:297-305, 1994. Pubmed reference: 7827752.
Vertel, B.M., Grier, B.L., Li, H., Schwartz, N.B. :
The chondrodystrophy, nanomelia: biosynthesis and processing of the defective aggrecan precursor Biochemical Journal 301:211-216, 1994. Pubmed reference: 8037674.
1993 Chandrasekaran, L., Tanzer, M.L. :
Molecular Cloning of Chicken Aggrecan (Vol 288, Pg 903, 1992) Biochemical Journal 296:885, 1993. Pubmed reference: 8280087.
Li, H., Schwartz, B., Vertel, B.M. :
cDNA Cloning of Chick Cartilage Chondroitin Sulfate (Aggrecan) Core Protein and Identification of a Stop Codon in the Aggrecan Gene Associated with the Chondrodystrophy, Nanomelia Journal of Biological Chemistry 268:23504-23511, 1993. Pubmed reference: 8226878.
Velleman, S.G., Haines, J.S., Pierro, L.J. :
Screening for Carriers of the Avian Cartilage Proteoglycan Core Protein Defect, Nanomelia, by Denaturing Gradient Gel Electrophoresis Journal of Heredity 84:147-149, 1993. Pubmed reference: 8228166.
Vertel, B.M., Walters, L.M., Grier, B., Maine, N., Goetinck, P.F. :
Nanomelic chondrocytes synthesize, but fail to translocate, a truncated aggrecan precursor. J Cell Sci :939-48, 1993. Pubmed reference: 8314884.
1992 Chandrasekaran, L., Tanzer, M.L. :
Molecular Cloning of Chicken Aggrecan - Structural Analyses Biochemical Journal 288:903-910, 1992. Pubmed reference: 1339285.
Velleman, S.G., Clark, S.H. :
The cartilage proteoglycan deficient mutation, nanomelia, contains a DNA polymorphism in the proteoglycan core protein gene that is genetically linked to the nanomelia phenotype. Matrix 12:66-72, 1992. Pubmed reference: 1560791.
Wong, M., Lawton, T., Goetinck, P.F., Kuhn, J.L., Goldstein, S.A., Bonadio, J. :
Aggrecan Core Protein Is Expressed in Membranous Bone of the Chick Embryo - Molecular and Biomechanical Studies of Normal and Nanomelia Embryos Journal of Biological Chemistry 267:5592-5598, 1992. Pubmed reference: 1372006.
1988 Goetinck, P.F. :
Studies on the avian chondrodysplasia mutant, nanomelia. Pathol Immunopathol Res 7:73-5, 1988. Pubmed reference: 3146751.
O'Donnell, C.M., Kaczman-Daniel, K., Goetinck, P.F., Vertel, B.M. :
Nanomelic chondrocytes synthesize a glycoprotein related to chondroitin sulfate proteoglycan core protein. J Biol Chem 263:17749-54, 1988. Pubmed reference: 3182870.
1987 Stirpe, N.S., Argraves, W.S., Goetinck, P.F. :
Chondrocytes from the cartilage proteoglycan-deficient mutant, nanomelia, synthesize greatly reduced levels of the proteoglycan core protein transcript Development Biology 124:77-81, 1987.
1983 McKeown-Longo, P.J., Velleman, S.G., Goetinck, P.F. :
The independent synthesis and secretion of cartilage proteoglycan and link protein by embryonic chicken chondrocytes. J Biol Chem 258:10779-85, 1983. Pubmed reference: 6885801.
1965 Landauer, W. :
Nanomelia, a lethal mutation of the fowl. J Hered 56:131-8, 1965. Pubmed reference: 14328419.

Edit History


  • Created by Frank Nicholas on 12 Sep 2005
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 31 Aug 2012