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71.
Summary The kinetics of replication of the inactive (late replicating) X chromosome (LRX) were studied in karyotypically normal lymphocytes and human amniotic fluid cells. Both cell types were successively pulse labeled with 1-h or 1/2-h thymidine pulses in an otherwise BrdU-substituted S phase after partial synchronization of the cultures at G1/S. For the first time with this technique, the entire sequence of replication was analyzed for the LRX from the beginning to the end of the S phase, with special reference to mid S (R-band to G-band transition replication). The inactive X is the last chromosome of the metaphase to start replication, with a delay of 1 or 2h, after which time a thymidine pulse results in R-type patterns. In mid S, the inactive X is the first chromosome to switch to G-type replication (without overlapping of both types and without any detectable replication pause). Until the end of S, a thymidine pulse results in G-type patterns. To rule out artifacts that might arise by the synchronization of cultures in these experiments, controls were carried out with BrdU pulses and the BrdU antibody technique without synchronization. In the course of replication, no fundamental difference was seen between the two different cell types examined. In contrast to studies using continuos labeling, this study did not reveal an interindividual difference of replication kinetics in the LRXs of the seven individuals studied; thus it is concluded that the inactive X chromosome shows only one characteristic course of replication. 相似文献
72.
Several reports in the literature suggest that many of the phenotypic defects of LPS-hyporesponsive C3H/HeJ mice may be attributed to decreased IFN production by their macrophages. The physical proximity on chromosome 4 of the gene which encodes sensitivity to LPS (Lps) and the structural gene cluster which encodes IFN-alpha (Ifa), suggests the possibility that the Lps gene, whose product is unknown, may actually be a part of the Ifa gene cluster. The C57BL/6J and C3H/HeJ mouse strains carry distinct alleles at both the LPs and the Ifa loci. In this study, we have analyzed these parental strains, as well as 12 recombinant inbred strains derived from these parental strains (e.g., BXH strains), for inheritance of these distinct alleles. The results show the segregation of these two loci: in 5 of 12 BXH RI strains, the IFN-alpha restriction fragment length polymorphism characteristic of one parental strain was discordant with the predicted LPS response phenotype. Therefore, we conclude that the Lps and the Ifa genes are physically distinct despite the apparent cause and effect relationship which is observed phenotypically. 相似文献
73.
The white and vermilion loci in D. melanogaster were selected as target genes for the study of the mutational specificity of ionizing radiation and N-ethyl-N-nitrosourea (ENU) in a whole organism. Analysis of X-ray- and neutron-induced white mutants by a combination of genetic and molecular techniques showed that ionizing radiation induces primarily break-type mutations against a repair-proficient background, the majority of these alterations being deletions. Both very large multi-locus deficiencies and deletions of only a few base pairs were observed. These small deletions are flanked by repeats of 2-3 nucleotides, one copy of which is retained at the new junction. Presumably these small repeats are involved in the generation of the X-ray-induced deletions. In excision-repair-deficient mus201D1 flies, the frequency of whole-body white mutants recovered after X-ray irradiation is the same as in the wild-type strain. The percentage of mosaic mutations, however, is enhanced by a factor 3-4. Analysis by blot hybridization of ENU-induced white mutants strongly indicates that most mutations are due to base-pair changes. This was confirmed by sequence analysis of 25 ENU-induced vermilion mutants. In all mutants the alterations are due to base-pair changes, the majority being GC to AT transitions (61%). 相似文献
74.
Xp-duplications with and without sex reversal 总被引:5,自引:0,他引:5
Annette Baumstark Gotthold Barbi Mahmoud Djalali Claudia Geerkens Beate Mitulla Torsten Mattfeldt José Carlos Cabral de Almeida Fernando Regla Vargas Juan Clinton Llerena Jr Walther Vogel Walter Just 《Human genetics》1996,97(1):79-86
Duplications in Xp including the DSS (dosage sensitive sex reversal) region cause male to female sex reversal. We investigated two patients from families with Xp duplications. The first case was one of two sisters with karyotype 46,XY, der(22), t(X;22)(p11.3;p11)mat and unambiguous female genitalia. The living sister was developmentally retarded, and showed multiple dysmorphic features and an acrocallosal syndrome. The second case was a boy with a maternally inherited direct duplication of Xp21.3-pter with the breakpoint close to the DSS locus. He had multiple abnormalities and micropenis, but otherwise unambiguous male genitalia. We performed quantitative Southern blot analysis with probes from Xp22.13 to p21.2 to define the duplicated region. Clinical, cytogenetic, and molecular data from both patients were compared with those of previously reported related cases. A comparison of the extragenital symptoms revealed no differences between patients with or without sex reversal. In both cases, the symptoms were non-specific. Among 22 patients with a duplication in Xp, nine had unambiguous female genitalia and a well-documented duplication of the DSS region. Two patients with duplication of DSS showed ambiguous external genitalia. From these data, we conclude that induction of testicular tissue may start in these patients, but that the type of genitalia depends on the degree of subsequent degeneration by a gene in DSS. 相似文献
75.
The Lys residues in the 75-residue Ca2+-binding protein calbindin D9k were reductively methylated with13C-enriched formaldehyde. The possible structural effects resulting from the chemical modification were critically investigated by comparing two-dimensional NMR spectra and the exchange rates of some of the amide protons of the native and the modified protein. Our results show that the protein retains its structure even though 10 Lys out of a total of 75 amino acid residues were modified. In the Ca2+- and apo-forms of the protein, the13C-methylated Lys residues can be detected with high sensitivity and resolution using two-dimensional (1H,13C)-heteronuclear multiple quantum coherence (HMQC) NMR spectroscopy. ThepKa values of the individual Lys residues in Ca2+-calbindin D9k and apo-calbindin D9k were obtained by combiningpH titration experiments and (1H,13C)-HMQC NMR spectroscopy. Each Lys residue in the Ca2+- and apo-forms of calbindin D9k has a uniquepKa value. The LyspKa values in the calcium protein range from 9.3 to 10.9, while those in the apo-protein vary between 9.7 and 10.7. Although apo-calbindin D9k has a very similar structure compared to Ca2+-calbindin D9k, the removal of two Ca2+ ions from the protein leads to an increase of thepKa values of the Lys residues. 相似文献
76.
77.
Genetic evidence for a functional relationship between Hsp104 and Hsp70. 总被引:12,自引:2,他引:10 下载免费PDF全文
Y Sanchez D A Parsell J Taulien J L Vogel E A Craig S Lindquist 《Journal of bacteriology》1993,175(20):6484-6491
The phenotypes of single Hsp104 and Hsp70 mutants of the budding yeast Saccharomyces cerevisiae provide no clue that these proteins are functionally related. Mutation of the HSP104 gene severely reduces the ability of cells to survive short exposures to extreme temperatures (thermotolerance) but has no effect on growth rates. On the other hand, mutations in the genes that encode Hsp70 proteins have significant effects on growth rates but do not reduce thermotolerance. The absence of a thermotolerance defect in S. cerevisiae Hsp70 mutants is puzzling, since the protein clearly plays an important role in thermotolerance in a variety of other organisms. In this report, examination of the phenotypes of combined Hsp104 and Hsp70 mutants uncovers similarities in the functions of Hsp104 and Hsp70 not previously apparent. In the absence of the Hsp104 protein, Hsp70 is very important for thermotolerance in S. cerevisiae, particularly at very early times after a temperature upshift. Similarly, Hsp104 plays a substantial role in vegetative growth under conditions of decreased Hsp70 protein levels. These results suggest a close functional relationship between Hsp104 and Hsp70. 相似文献
78.
Gundula Thiel Tanka Lozanova Siegfried Vogel Dieter Kintzel Werner Jänisch Regine Witkowski 《Human genetics》1993,91(6):547-550
We report a cytogenetic investigation of 55 low-grade astrocytomas in 52 patients, 15 children and 37 adults. In addition to numerical aberrations such as trisomy 7 and gonosomal losses, we found structural and/or numerical aberrations of chromosome 1 in eight astrocytomas. There was a striking difference between the rearranged chromosomes in pediatric and adult patients. Whereas the pediatric tumors revealed monosomies 1p with accompanying trisomy 1q, the astrocytomas in adults showed partial or complete monosomies 1q. 相似文献
79.
80.