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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Inbreeding


High impact information on Inbreeding

  • Three cycles of shuffling and two cycles of backcrossing with wild-type DNA, to eliminate non-essential mutations, were each followed by selection on increasing concentrations of the antibiotic cefotaxime [6].
  • Repeated backcrossing from Mta+ females to NZB or NMRI males has shown that, given the right cytoplasmic genes, the chromosomal genes of these Mta- strains permit expression of Mta2 [7].
  • By backcrossing into the Ws and Landsberg erecta genetic backgrounds, we constructed sibling pairs of PHYD+ and phyD-1 lines and of phyB- PHYD+ and phyB- phyD- lines [8].
  • The high inbreeding coefficients found in these eusocial thrips have increased relatedness among and within both sexes and have reduced the haplodiploidy-induced relatedness asymmetries [Hamilton, W. D. (1964) J. Theor. Biol. 7, 1-52] [9].
  • Generation and negative selection of NK1.1(+)alpha/beta T cell receptor (TCR)+ thymocytes were analyzed using TCR-transgenic (B10. D2 x DO10)F1 and (C57BL/6 x DO10)F1 mice and Rag-1(-/-)/DO10 mice, which had been established by breeding and backcrossing between Rag-1(-/-) and DO10 mice [10].

Chemical compound and disease context of Inbreeding

  • We demonstrate that tetracycline treatment of adult Ae. albopictus can predictably generate uninfected individuals, simplify the procedure required for Wolbachia removal, and reduce the level of inbreeding required to produce uninfected lines [11].

Biological context of Inbreeding

  • Here we characterize an LDL receptor mutation that is associated with a distinct haplotype and causes FH in the Druze, a small Middle Eastern Islamic sect with a high degree of inbreeding [12].
  • Although some plants apparently have multiple integration sites, analysis of progeny obtained by self-fertilization of the transgenic plants indicates that the kanamycin-resistance marker is inherited as a single dominant gene [13].
  • After backcrossing the knockout mutation onto the NOD genetic background for up to eight generations, female littermates of the three resulting genotypes were produced by intercrossing: GAD65 +/+ (n=23), GAD65 +/- (n=62), and GAD65 -/- (n=31) [14].
  • The logarithm of odds (Lod) score analyzed from the family with inbreeding (R) was compatible with linkage of disease and the TPO gene (Lod = 2.08) [15].
  • After backcrossing with the Landsberg erecta (Ler) wild-type (WT) followed by selfing, the mutant phenotype was identified in the GA4 background [16].

Anatomical context of Inbreeding

  • These results suggest that the long history of inbreeding for high tumor incidence of C3H and R111 mouse strains has selected for the fixation of host mutations which either complement the action of the particular int gene or affect the sensitivity of specific subpopulations of mammary epithelium to infection by particular strains of MMTV [17].
  • In this study, the relationship between inbreeding and semen quality was examined in 285 immature Shetland pony stallions submitted for breeding soundness examination in March-April of the years 1992-1997 [18].

Associations of Inbreeding with chemical compounds

  • DRH strain rats were established by inbreeding a closed colony of Donryu rats continuously fed the chemical hepatocarcinogen 3'-methyl-4-dimethylaminoazobenzene for over 10 years [19].
  • Repeated backcrossing of F1 with W rats successively improved glucose tolerance [20].
  • ALS is an inbred strain with low antioxidant defenses produced by inbreeding CD-1 mice, with selection for susceptibility to alloxan, a generator of highly reactive oxygen free radicals and a potent beta-cell toxin [21].
  • Further work, however, is required to clarify whether the cholesterol trait is related to the etiology of stroke or has been retained by chance through the inbreeding process in SHRSP [22].
  • By crossing replicates of the M lines with the C16 control, the effects of inbreeding depression were removed [23].

Gene context of Inbreeding

  • Exaggerated sex-dependent variations in metabolism by rats may be the result of extensive inbreeding and/or differential evolution of isoforms of cytochromes P450 in mammals [24].
  • We created a congenic strain with reduced (approximately 20%) circulating IGF-I (C3H.B6-6T [6T]) by backcrossing a small genomic region (30 cM) of Chromosome 6 (Chr6) from C3H/HeJ (C3H) onto a C57Bl/6J (B6) background [25].
  • Multipoint linkage analysis, using a simplified pedigree structure for the family (which contains 192 individuals and two inbreeding loops), gave a maximum lod score of 12.2 for RP1 at a distance 8.1 cM proximal to PLAT in the pericentric region of the chromosome [26].
  • Murine Ptx1 was localized, by interspecific backcrossing, to Chr 13 within 2.6 cM of Caml [27].
  • We have created congenic lines (F(chr15L)), by recurrent marker-assisted backcrossing, to introgress the QTL region with the highest LOD score, Fob3 on Chr 15, from the L-Iine into the F-line background [28].

Analytical, diagnostic and therapeutic context of Inbreeding


  1. Furazolidone-induced cardiomyopathy in turkeys. Association with a relative alpha1-antitrypsin deficiency. Staley, N.A., Noren, G.R., Bandt, C.M., Sharp, H.L. Am. J. Pathol. (1978) [Pubmed]
  2. Reflections on muscular dystrophy in a Sudanese kindred. Salih, M.A., Roberts, D.F., Omer, M.I., Karrar, O., Bayoumi, R.A. Clin. Genet. (1983) [Pubmed]
  3. Genetic analysis of multiple sclerosis in Orkney. Roberts, D.F., Roberts, M.J., Poskanzer, D.C. Journal of epidemiology and community health. (1979) [Pubmed]
  4. The paradoxical effects of interleukin 10 in the immunoregulation of autoimmune diabetes. Balasa, B., Sarvetnick, N. J. Autoimmun. (1996) [Pubmed]
  5. Autoimmunity and glomerulonephritis in mice with targeted deletion of the serum amyloid P component gene: SAP deficiency or strain combination? Gillmore, J.D., Hutchinson, W.L., Herbert, J., Bybee, A., Mitchell, D.A., Hasserjian, R.P., Yamamura, K., Suzuki, M., Sabin, C.A., Pepys, M.B. Immunology (2004) [Pubmed]
  6. Rapid evolution of a protein in vitro by DNA shuffling. Stemmer, W.P. Nature (1994) [Pubmed]
  7. A new H-2-linked class I gene whose expression depends on a maternally inherited factor. Lindahl, K.F., Hausmann, B., Chapman, V.M. Nature (1983) [Pubmed]
  8. A deletion in the PHYD gene of the Arabidopsis Wassilewskija ecotype defines a role for phytochrome D in red/far-red light sensing. Aukerman, M.J., Hirschfeld, M., Wester, L., Weaver, M., Clack, T., Amasino, R.M., Sharrock, R.A. Plant Cell (1997) [Pubmed]
  9. High relatedness and inbreeding at the origin of eusociality in gall-inducing thrips. Chapman, T.W., Crespi, B.J., Kranz, B.D., Schwarz, M.P. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  10. Intrathymic selection of NK1.1(+)alpha/beta T cell antigen receptor (TCR)+ cells in transgenic mice bearing TCR specific for chicken ovalbumin and restricted to I-Ad. Iwabuchi, C., Iwabuchi, K., Nakagawa, K., Takayanagi, T., Nishihori, H., Tone, S., Ogasawara, K., Good, R.A., Onoé, K. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  11. A novel technique for removing Wolbachia infections from Aedes albopictus (Diptera: Culicidae). Dobson, S.L., Rattanadechakul, W. J. Med. Entomol. (2001) [Pubmed]
  12. A nonsense mutation in the LDL receptor gene leads to familial hypercholesterolemia in the Druze sect. Landsberger, D., Meiner, V., Reshef, A., Levy, Y., van der Westhuyzen, D.R., Coetzee, G.A., Leitersdorf, E. Am. J. Hum. Genet. (1992) [Pubmed]
  13. Stable transformation of tobacco by electroporation: evidence for plasmid concatenation. Riggs, C.D., Bates, G.W. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  14. Development of autoimmune diabetes in glutamic acid decarboxylase 65 (GAD65) knockout NOD mice. Yamamoto, T., Yamato, E., Tashiro, F., Sato, T., Noso, S., Ikegami, H., Tamura, S., Yanagawa, Y., Miyazaki, J.I. Diabetologia (2004) [Pubmed]
  15. Genetic linkage studies of thyroid peroxidase (TPO) gene in families with TPO deficiency. Mangklabruks, A., Billerbeck, A.E., Wajchenberg, B., Knobel, M., Cox, N.J., DeGroot, L.J., Medeiros-Neto, G. J. Clin. Endocrinol. Metab. (1991) [Pubmed]
  16. The ELONGATED gene of Arabidopsis acts independently of light and gibberellins in the control of elongation growth. Halliday, K., Devlin, P.F., Whitelam, G.C., Hanhart, C., Koornneef, M. Plant J. (1996) [Pubmed]
  17. Host genetic background effect on the frequency of mouse mammary tumor virus-induced rearrangements of the int-1 and int-2 loci in mouse mammary tumors. Marchetti, A., Robbins, J., Campbell, G., Buttitta, F., Squartini, F., Bistocchi, M., Callahan, R. J. Virol. (1991) [Pubmed]
  18. Possible negative effects of inbreeding on semen quality in Shetland pony stallions. van Eldik, P., van der Waaij, E.H., Ducro, B., Kooper, A.W., Stout, T.A., Colenbrander, B. Theriogenology (2006) [Pubmed]
  19. Genetic resistance to chemical carcinogen-induced preneoplastic hepatic lesions in DRH strain rats. Zeng, Z.Z., Higashi, S., Kitayama, W., Denda, A., Yan, Y., Matsuo, K., Konishi, Y., Hiai, H., Higashi, K. Cancer Res. (2000) [Pubmed]
  20. Impact of diabetic inheritance on glucose tolerance and insulin secretion in spontaneously diabetic GK-Wistar rats. Abdel-Halim, S.M., Guenifi, A., Luthman, H., Grill, V., Efendic, S., Ostenson, C.G. Diabetes (1994) [Pubmed]
  21. ALS/Lt: a new type 2 diabetes mouse model associated with low free radical scavenging potential. Mathews, C.E., Bagley, R., Leiter, E.H. Diabetes (2004) [Pubmed]
  22. Identification of quantitative trait loci for serum cholesterol levels in stroke-prone spontaneously hypertensive rats. Kato, N., Tamada, T., Nabika, T., Ueno, K., Gotoda, T., Matsumoto, C., Mashimo, T., Sawamura, M., Ikeda, K., Nara, Y., Yamori, Y. Arterioscler. Thromb. Vasc. Biol. (2000) [Pubmed]
  23. Population size and selection intensity effects on long-term selection response in mice. Eisen, E.J. Genetics (1975) [Pubmed]
  24. Sex-dependent metabolism of xenobiotics. Mugford, C.A., Kedderis, G.L. Drug Metab. Rev. (1998) [Pubmed]
  25. Congenic mice with low serum IGF-I have increased body fat, reduced bone mineral density, and an altered osteoblast differentiation program. Rosen, C.J., Ackert-Bicknell, C.L., Adamo, M.L., Shultz, K.L., Rubin, J., Donahue, L.R., Horton, L.G., Delahunty, K.M., Beamer, W.G., Sipos, J., Clemmons, D., Nelson, T., Bouxsein, M.L., Horowitz, M. Bone (2004) [Pubmed]
  26. Linkage mapping of autosomal dominant retinitis pigmentosa (RP1) to the pericentric region of human chromosome 8. Blanton, S.H., Heckenlively, J.R., Cottingham, A.W., Friedman, J., Sadler, L.A., Wagner, M., Friedman, L.H., Daiger, S.P. Genomics (1991) [Pubmed]
  27. Human and murine PTX1/Ptx1 gene maps to the region for Treacher Collins syndrome. Crawford, M.J., Lanctôt, C., Tremblay, J.J., Jenkins, N., Gilbert, D., Copeland, N., Beatty, B., Drouin, J. Mamm. Genome (1997) [Pubmed]
  28. Genetic complexity of an obesity QTL ( Fob3) revealed by detailed genetic mapping. Stylianou, I.M., Christians, J.K., Keightley, P.D., Bünger, L., Clinton, M., Bulfield, G., Horvat, S. Mamm. Genome (2004) [Pubmed]
  29. The influence of sex on extracellular dopamine and locomotor activity in C57BL/6J mice before and after acute cocaine challenge. Griffin, W.C., Middaugh, L.D. Synapse (2006) [Pubmed]
  30. Genetic epidemiology of cystic fibrosis in Saguenay-Lac-St-Jean (Quebec, Canada). Daigneault, J., Aubin, G., Simard, F., De Braekeleer, M. Clin. Genet. (1991) [Pubmed]
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