Disease relevance of Inbreeding

• A naturally occurring cardiomyopathy (round heart disease) which is potentiated by inbreeding and a cardiomyopathy produced by furazolidone, a nitrofuran derivative, were studied for an associated alpha1-antitrypsin deficiency in two flocks of turkeys (one inbred for round heart disease and a commercial flock) [1].
• The within-sibship ratio, the autosomal and X-linked inbreeding coefficients, and the creatine kinase levels suggest a possible alternative interpretation: X-linked muscular dystrophy with failure of clinical expression in some males [2].
• In a family study of all patients with multiple sclerosis (MS) in Orkney, the number of inbred among patients, although high for Britain, is not higher than the number among controls, and the inbreeding coefficients appear to eliminate recessive involvement of rare genes from the aetiology [3].
• However, backcrossing of these Tg mice with NOD mice accelerated the onset of diabetes, indicating a pathogenic role for IL-10 in the pathogenesis of autoimmune diabetes since it is able to replace the genetic susceptibility information on the NOD genome [4].
• SAP-deficient animals, created by backcrossing the 129/Sv SAP gene deletion into pure line C57BL/6 mice and studied here for the first time, also spontaneously developed broad spectrum antinuclear autoimmunity and proliferative immune complex glomerulonephritis but without proteinuria, renal failure, or increased morbidity or mortality [5].

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

• C57BL6/J (C57) mice serve as a useful animal model of cocaine abuse because they self-administer cocaine, exhibit place conditioning to cocaine, discriminate the interoceptive cues of cocaine, and are used for backcrossing strains of genetically modified mice [29].
• The mean inbreeding coefficient was only slightly elevated in the CF group compared with three control groups, and was due to remote consanguinity [30].

References