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排序方式: 共有70条查询结果,搜索用时 15 毫秒
1.
N B Spinner D L Eunpu R D Schmickel E H Zackai D McEldrew G R Bunin H McDermid B S Emanuel 《American journal of human genetics》1989,44(5):631-638
Silver-stained chromosomes from 29 couples with a trisomy 21 offspring and from 25 control couples were studied to determine whether there was an association of nucleolar-organizing-region variants in parents of children with trisomy 21. A reproducible scoring system for the analysis of silver-stained chromosomes was developed, and this was applied to the analysis of study participants in a blinded fashion. Seven of the 58 parents of children with trisomy 21 and seven of the 50 control parents were found to have variant NORs on silver staining. Therefore, we do not find a demonstrable risk for nondisjunction of chromosome 21 in individuals with silver-staining variants. 相似文献
2.
Polymorphisms of mitochondrially encoded proteins can be detected in human lymphocytes by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Using an SDS-polyacrylamide 8 M urea system, 17 mitochondrially encoded proteins are distinguishable. Three of these (ME-6, ME-8, and ME-17) were polymorphic among 92 individuals screened, and these polymorphisms are reported here for the first time. With SDS-polyacrylamide electrophoresis without urea, 18 mitochondrial proteins are detectable. One of these (MV-1) varied in two of 31 individuals tested. This polymorphism has been identified previously in HeLa cells. Maternal inheritance of the ME-8 polymorphism was demonstrated by three informative families. 相似文献
3.
Molecular analysis of 24 Alagille syndrome families identifies a single submicroscopic deletion and further localizes the Alagille region within 20p12. 总被引:1,自引:1,他引:0 下载免费PDF全文
E B Rand N B Spinner D A Piccoli P F Whitington R Taub 《American journal of human genetics》1995,57(5):1068-1073
Alagille syndrome (AGS) is a clinically defined disorder characterized by cholestatic liver disease with bile duct paucity, peculiar facies, structural heart defects, vertebral anomalies, and ocular abnormalities. Multiple patients with various cytogenetic abnormalities involving 20p12 have been identified, allowing the assignment of AGS to this region. The presence of interstitial deletions of varying size led to the hypothesis that AGS is a contiguous gene deletion syndrome. This molecular analysis of cytogenetically normal AGS patients was performed in order to test this hypothesis and to refine the localization of the known AGS region. Investigation of inheritance of simple tandem repeat polymorphism alleles in 67 members of 24 cytogenetically normal Alagille families led to the identification of a single submicroscopic deletion. The deletion included loci D20S61, D20S41, D20S186, and D20S188 and presumably intervening uninformative loci D20S189 and D20S27. The six deleted loci are contained in a single YAC of 1.9 Mb. The additional finding of multiple unrelated probands who are heterozygous at each locus demonstrates that microdeletions at known loci within the AGS region are rare in cytogenetically normal patients with this disorder. This suggests that the majority of cases of AGS may be the result of a single gene defect rather than a contiguous gene deletion syndrome. 相似文献
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5.
Mutations of Jagged 1 (JAG1), a ligand in the Notch signaling pathway, cause Alagille syndrome (AGS). AGS is an autosomal dominant, multisystem disorder with variable expressivity, characterized by bile duct paucity and resultant liver disease in combination with cardiac, ocular, skeletal, and facial findings. JAG1 mutations in AGS include gene deletions and protein truncating, splicing, and missense mutations, suggesting that haploinsufficiency is the mechanism of disease causation. With limited exceptions, there is no genotype-phenotype correlation. We have studied a JAG1 missense mutation (JAG1-G274D) that was previously identified in 13 individuals from an extended family with cardiac defects of the type seen in patients with AGS (e.g., peripheral pulmonic stenosis and tetralogy of Fallot) in the absence of liver dysfunction. Our data indicate that this mutation is "leaky." Two populations of proteins are produced from this allele. One population is abnormally glycosylated and is retained intracellularly rather than being transported to the cell surface. A second population is normally glycosylated and is transported to the cell surface, where it is able to signal to the Notch receptor. The JAG1-G274D protein is temperature sensitive, with more abnormally glycosylated (and nonfunctional) molecules produced at higher temperatures. Carriers of this mutation therefore have >50% but <100% of the normal concentration of JAG1 molecules on the cell surface. The cardiac-specific phenotype associated with this mutation suggests that the developing heart is more sensitive than the developing liver to decreased dosage of JAG1. 相似文献
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7.
Chen EC Yagi S Kelly KR Mendoza SP Tarara RP Canfield DR Maninger N Rosenthal A Spinner A Bales KL Schnurr DP Lerche NW Chiu CY 《PLoS pathogens》2011,7(7):e1002155
Adenoviruses are DNA viruses that naturally infect many vertebrates, including humans and monkeys, and cause a wide range of clinical illnesses in humans. Infection from individual strains has conventionally been thought to be species-specific. Here we applied the Virochip, a pan-viral microarray, to identify a novel adenovirus (TMAdV, titi monkey adenovirus) as the cause of a deadly outbreak in a closed colony of New World monkeys (titi monkeys; Callicebus cupreus) at the California National Primate Research Center (CNPRC). Among 65 titi monkeys housed in a building, 23 (34%) developed upper respiratory symptoms that progressed to fulminant pneumonia and hepatitis, and 19 of 23 monkeys, or 83% of those infected, died or were humanely euthanized. Whole-genome sequencing of TMAdV revealed that this adenovirus is a new species and highly divergent, sharing <57% pairwise nucleotide identity with other adenoviruses. Cultivation of TMAdV was successful in a human A549 lung adenocarcinoma cell line, but not in primary or established monkey kidney cells. At the onset of the outbreak, the researcher in closest contact with the monkeys developed an acute respiratory illness, with symptoms persisting for 4 weeks, and had a convalescent serum sample seropositive for TMAdV. A clinically ill family member, despite having no contact with the CNPRC, also tested positive, and screening of a set of 81 random adult blood donors from the Western United States detected TMAdV-specific neutralizing antibodies in 2 individuals (2/81, or 2.5%). These findings raise the possibility of zoonotic infection by TMAdV and human-to-human transmission of the virus in the population. Given the unusually high case fatality rate from the outbreak (83%), it is unlikely that titi monkeys are the native host species for TMAdV, and the natural reservoir of the virus is still unknown. The discovery of TMAdV, a novel adenovirus with the capacity to infect both monkeys and humans, suggests that adenoviruses should be monitored closely as potential causes of cross-species outbreaks. 相似文献
8.
9.
Replication slippage may cause parallel evolution in the secondary structures of mitochondrial transfer RNAs 总被引:9,自引:4,他引:5
Presence of the dihydrouridine (D) stem in the mitochondrial cysteine tRNA
is unusually variable among lepidosaurian reptiles. Phylogenetic and
comparative analyses of cysteine tRNA gene sequences identify eight
parallel losses of the D-stem, resulting in D-arm replacement loops.
Sampling within the monophyletic Acrodonta provides no evidence for
reversal. Slipped-strand mispairing of noncontiguous repeated sequences
during replication or direct replication slippage can explain repeats
observed within cysteine tRNAs that contain a D-arm replacement loop. These
two mechanisms involving replication slippage can account for the loss of
the cysteine tRNA D-stem in several lepidosaurian lineages, and may
represent general mechanisms by which the secondary structures of
mitochondrial tRNAs are altered.
相似文献
10.
Zhao Y Thornton AM Kinney MC Ma CA Spinner JJ Fuss IJ Shevach EM Jain A 《The Journal of biological chemistry》2011,286(47):40520-40530
CYLD is a lysine 63-deubiquitinating enzyme that inhibits NF-κB and JNK signaling. Here, we show that CYLD knock-out mice have markedly increased numbers of regulatory T cells (Tregs) in peripheral lymphoid organs but not in the thymus. In vitro stimulation of CYLD-deficient naive T cells with anti-CD3/28 in the presence of TGF-β led to a marked increase in the number of Foxp3-expressing T cells when compared with stimulated naive control CD4(+) cells. Under endogenous conditions, CYLD formed a complex with Smad7 that facilitated CYLD deubiquitination of Smad7 at lysine 360 and 374 residues. Moreover, this site-specific ubiquitination of Smad7 was required for activation of TAK1 and p38 kinases. Finally, knockdown of Smad7 or inhibition of p38 activity in primary T cells impaired Treg differentiation. Together, our results show that CYLD regulates TGF-β signaling function in T cells and the development of Tregs through deubiquitination of Smad7. 相似文献