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Gene Review

Tcd1a  -  t-complex distorter 1A

Mus musculus

Synonyms: TRD, Tcd-1, Tcd1, tcs-1, tcs1
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Disease relevance of Tcd1a

  • One deletion, T(30H), together with three others, T(31H), T(33H), and T(36H), which extended more proximally, caused male sterility when heterozygous with a complete t haplotype and also enhanced transmission ratio of the partial t haplotype t(6), and this was attributed to deletion of the Tcd1 locus [1].
  • We find that the distorter activity of Tcd1 is distinct from a linked sterility factor, originally called tcs1 [2].

High impact information on Tcd1a

  • Tagap1 maps to the Tcd1 interval and has four t loci, which encode altered proteins including a C-terminally truncated form [3].
  • Combined with the recent identification of another putative t complex distorter, Tctex2, within the outer dynein arm, these results support the hypothesis that transmission ratio distortion (meiotic drive) of mouse t haplotypes involves dysfunction of both flagellar inner and outer dynein arms but does not require the cytoplasmic isozyme [4].
  • In this, study a transgenic approach was used to identify the proximal sterility locus, tcs1 (S1), and test its role in TRD [5].
  • The mouse t complex distorter/sterility candidate, Dnahc8, expresses a gamma-type axonemal dynein heavy chain isoform confined to the principal piece of the sperm tail [6].
  • Heterozygosity for a t haplotype (t) in male mice results in distorted transmission (TRD) of the t-bearing chromosome 17 homolog to their offspring [6].

Biological context of Tcd1a

  • One factor, Tcd1, was previously shown to be amorphic using a chromosome deletion [2].
  • Sperm carrying the responder locus (Tcr) have a high probability of fertilizing eggs at the expense of wild-type sperm, provided that distorter loci (Tcd-1 to Tcd-5) are expressed during spermatogenesis [7].
  • This analysis shows that segmental exchange, either by gene conversion or double crossing-over, has occurred at molecular markers in the vicinity of a gene, Dnahc8, that is a candidate for the t complex distorter locus Tcd2 [8].
  • The Ca(2+)-dependent sperm tail curvature phenotypes, "fishhook", where abnormally high levels of sperm exhibit sharp bends in the midpiece, and "curlicue", where motile sperm exhibit a chronic negative curving of the entire tail, have been tightly linked to t-associated male TRD and sterility traits, respectively [6].
  • RESULTS: The Tg8 line of transgene carriers had a significant (P < 0.001) TRD, due to reduced fertilizing ability of transgene-bearing sperm [9].

Anatomical context of Tcd1a

  • Genomic structure around joining segments and constant regions of swine T-cell receptor alpha/delta (TRA/TRD) locus [10].
  • In these animals, V(D)J rearrangements are detected in thymus, lymph nodes, and spleen at the TRB locus, and in thymus and lymph nodes at the TRD locus [11].
  • Our earlier studies on carriers of spontaneous mutations of mouse Sperm Adhesion Molecule 1 (Spam1) suggested that TRD results from biochemically different sperm, due to a lack of transcript sharing through the intercellular cytoplasmic bridges of spermatids [9].

Other interactions of Tcd1a

  • To overcome limitations imposed by recombination suppression, we used a series of deletions within the t complex in trans to t chromosomes to characterize the Tcd1 region [2].
  • It is suggested that the original distorter Tcd1 in fact consists of two loci: Tcd1a, lying between D17Mit164 and D17Leh48, and Tcd1b, lying between T and D17Leh66E [1].
  • An allele of the mouse brachyury locus, T22H, had been shown previously to involve a deletion of several markers in the proximal part of chromosome 17, and almost certainly includes deletion of the t-complex distorter gene Tcd-1 [12].
  • YACs mapped with respect to deletion breakpoints localize tcs1 to a 1.1-Mb interval flanked by D17Aus9 and Tctex1 [2].
  • The possibility that the Sod-2 locus is related to some of the t-complex distorter or responder loci is discussed [13].

Analytical, diagnostic and therapeutic context of Tcd1a

  • METHODS: Carriers of Spam1-Hyal5 BAC transgenes were mated with wild-type female mice and the progeny analyzed for TRD by PCR genotyping [9].


  1. Narrowing the critical regions for mouse t complex transmission ratio distortion factors by use of deletions. Lyon, M.F., Schimenti, J.C., Evans, E.P. Genetics (2000) [Pubmed]
  2. Physical mapping of male fertility and meiotic drive quantitative trait loci in the mouse t complex using chromosome deficiencies. Planchart, A., You, Y., Schimenti, J.C. Genetics (2000) [Pubmed]
  3. The t complex-encoded GTPase-activating protein Tagap1 acts as a transmission ratio distorter in mice. Bauer, H., Willert, J., Koschorz, B., Herrmann, B.G. Nat. Genet. (2005) [Pubmed]
  4. Identification of the t complex-encoded cytoplasmic dynein light chain tctex1 in inner arm I1 supports the involvement of flagellar dyneins in meiotic drive. Harrison, A., Olds-Clarke, P., King, S.M. J. Cell Biol. (1998) [Pubmed]
  5. Mutations in Serac1 or Synj2 cause proximal t haplotype-mediated male mouse sterility but not transmission ratio distortion. Schimenti, J.C., Reynolds, J.L., Planchart, A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  6. The mouse t complex distorter/sterility candidate, Dnahc8, expresses a gamma-type axonemal dynein heavy chain isoform confined to the principal piece of the sperm tail. Samant, S.A., Ogunkua, O.O., Hui, L., Lu, J., Han, Y., Orth, J.M., Pilder, S.H. Dev. Biol. (2005) [Pubmed]
  7. The mouse Rsk3 gene maps to the Leh66 elements carrying the t-complex responder Tcr. Kispert, A., Stöger, R.J., Caparros, M., Herrmann, B.G. Mamm. Genome (1999) [Pubmed]
  8. Pattern of segmental recombination in the distal inversion of mouse t haplotypes. Erhart, M.A., Lekgothoane, S., Grenier, J., Nadeau, J.H. Mamm. Genome (2002) [Pubmed]
  9. Spam1-associated transmission ratio distortion in mice: elucidating the mechanism. Martin-DeLeon, P.A., Zhang, H., Morales, C.R., Zhao, Y., Rulon, M., Barnoski, B.L., Chen, H., Galileo, D.S. Reprod. Biol. Endocrinol. (2005) [Pubmed]
  10. Genomic structure around joining segments and constant regions of swine T-cell receptor alpha/delta (TRA/TRD) locus. Uenishi, H., Hiraiwa, H., Yamamoto, R., Yasue, H., Takagaki, Y., Shiina, T., Kikkawa, E., Inoko, H., Awata, T. Immunology (2003) [Pubmed]
  11. Partial reconstitution of V(D)J rearrangement and lymphocyte development in RAG-deficient mice expressing inducible, tetracycline-regulated RAG transgenes. Shockett, P.E., Zhou, S., Hong, X., Schatz, D.G. Mol. Immunol. (2004) [Pubmed]
  12. Deletion of mouse t-complex distorter-1 produces an effect like that of the t-form of the distorter. Lyon, M.F. Genet. Res. (1992) [Pubmed]
  13. Mapping of the Sod-2 locus into the t complex on mouse chromosome 17. Figueroa, F., Vincek, V., Kasahara, M., Bell, G.I., Klein, J. Immunogenetics (1988) [Pubmed]
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