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P M Frossard P A Gonzalez L C Fritz P A Ponte J C Fiddes S A Atlas 《Nucleic acids research》1986,14(10):4380
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We report the identification of a TaqI dimorphic site in the first intron of a human phospholipase A2 gene that has been localized on chromosome 12. This single two-allele polymorphism was detected by DNA blot hybridization using a full-length, 584 bp human phospholipase A2 cDNA isolated from a human lung gt10 cDNA library. Fragment lengths were detected at either 1.3 kb or 2.2 kb. The PIC value of this dimorphism was 0.369 in a random population of 353 Caucasians. 相似文献
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Litman GW; Rast JP; Shamblott MJ; Haire RN; Hulst M; Roess W; Litman RT; Hinds- Frey KR; Zilch A; Amemiya CT 《Molecular biology and evolution》1993,10(1):60-72
Immunoglobulins are encoded by a large multigene system that undergoes
somatic rearrangement and additional genetic change during the development
of immunoglobulin-producing cells. Inducible antibody and antibody-like
responses are found in all vertebrates. However, immunoglobulin possessing
disulfide-bonded heavy and light chains and domain-type organization has
been described only in representatives of the jawed vertebrates. High
degrees of nucleotide and predicted amino acid sequence identity are
evident when the segmental elements that constitute the immunoglobulin gene
loci in phylogenetically divergent vertebrates are compared. However, the
organization of gene loci and the manner in which the independent elements
recombine (and diversify) vary markedly among different taxa. One striking
pattern of gene organization is the "cluster type" that appears to be
restricted to the chondrichthyes (cartilaginous fishes) and limits
segmental rearrangement to closely linked elements. This type of gene
organization is associated with both heavy- and light-chain gene loci. In
some cases, the clusters are "joined" or "partially joined" in the germ
line, in effect predetermining or partially predetermining, respectively,
the encoded specificities (the assumption being that these are expressed)
of the individual loci. By relating the sequences of transcribed gene
products to their respective germ-line genes, it is evident that, in some
cases, joined-type genes are expressed. This raises a question about the
existence and/or nature of allelic exclusion in these species. The
extensive variation in gene organization found throughout the vertebrate
species may relate directly to the role of intersegmental
(V<==>D<==>J) distances in the commitment of the individual
antibody-producing cell to a particular genetic specificity. Thus, the
evolution of this locus, perhaps more so than that of others, may reflect
the interrelationships between genetic organization and function.
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Toluene diisocyanate (TDI) is a highly volatile chemical known to cause occupational asthma in exposed workers. TDI-induced asthma is associated with airway epithelium injury and repair, and subepithelial fibrosis. We investigated the effect of TDI and its hydrolysis products, the 2,4- and 2,6-toluenediamines (TDA), on viability and growth of human lung fibroblasts (HLFs) in culture, using a tetrazolium-based cell viability assay. The effects of increasing concentrations of each of these chemicals were evaluated on quiescent cells seeded at two densities (2500 and 5000 cells/well) and treated for 24 or 48 h. TDI (10–4–10–5 mol/L, as a mixture of 80% 2,4-TDI and 20% 2,6-TDI) exhibited a partial but significant cytotoxic effect (10–24%, p<0.05) on HLFs. This effect was observed at both cell densities, and was time- and concentration-dependent. 2,4-TDA, at lower concentrations (10–8–10–6 mol/L) applied for 48 h, also partially reduced HLF viability (10–15%, p<0.05), whereas it tended to trigger cell growth at concentrations higher than 10–5 mol/L. 2,6-TDA exhibited both a cytotoxic and a proliferative effect on HLFs that depended on concentration, time of exposure and cell culture density. Significant cytotoxicity was only observed after 24 h of treatment with 10–7–10–6 mol/L 2,6-TDA, and reached greater intensity in cells cultured at the highest density. In contrast, 2,6-TDA stimulated HLF growth only after 48 h of incubation at 10–4 mol/L on cells cultured at the lowest density. Taken together, our results showed that TDI and 2,4-TDA somewhat decreased HLF viability, whereas 2,6-TDA appeared to exhibit both a cytotoxic and a growth stimulatory effect on these cells. TDI and 2,4-TDA are thus suggested to contribute to airway epithelium damage associated with TDI-induced asthma, whereas 2,6-TDA might either trigger epithelial damage or induce cell proliferation that could contribute to epithelium repair or subepithelial fibrosis. 相似文献
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