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101.
102.
Francis MJ; Jones EE; Levy ER; Ponnambalam S; Chelly J; Monaco AP 《Human molecular genetics》1998,7(8):1245-1252
Menkes disease arises from a genetic impairment in copper transport. The
gene responsible for the phenotype has been identified as a copper
transporting ATPase ( ATP7A ). Recently, the protein encoded by the ATP7A
gene has been localized to the Golgi complex. In order to investigate the
role of the Menkes disease protein in copper transport, recombinant
constructs containing both the full-length open reading frame and an
alternatively spliced form have been successfully expressed and localized
in mammalian cells. Other studies of a patient with occipital horn
syndrome, an allelic variant of Menkes disease, have demonstrated that only
this alternatively spliced isoform and not the full-length form is
expressed in this patient. The milder form of this patient's phenotype
suggests that the alternatively spliced isoform has some functional role in
copper transport. In the present study the full-length recombinant Menkes
protein was shown by immunofluorescence to localize to the Golgi apparatus
and the alternatively spliced form, lacking sequences for transmembrane
domains 3 and 4 encoded by exon 10, was shown to localize to the
endoplasmic reticulum. Using sequences from exon 10 fused to a non-Golgi
reporter molecule, a 38 amino acid sequence containing transmembrane domain
3 of the Menkes protein was found to be sufficient for localization to the
Golgi complex. Therefore, the protein sequence encoded by exon 10 may be
responsible for this differential localization and both isoforms may be
required for comprehensive transport of copper within the cell.
相似文献
103.
Wanker EE; Rovira C; Scherzinger E; Hasenbank R; Walter S; Tait D; Colicelli J; Lehrach H 《Human molecular genetics》1997,6(3):487-495
We report the discovery of the huntingtin interacting protein I (HIP-I)
which binds specifically to the N-terminus of human huntingtin, both in the
two-hybrid screen and in in vitro binding experiments. For the interaction
in vivo, a protein region downstream of the polyglutamine stretch in
huntingtin is essential. The HIP1 cDNA isolated by the two- hybrid screen
encodes a 55 kDa fragment of a novel protein. Using an affinity-purified
polyclonal antibody raised against recombinant HIP-I, a protein of 116 kDa
was detected in brain extracts by Western blot analysis. The predicted
amino acid sequence of the HIP-I fragment exhibits significant similarity
to cytoskeleton proteins, suggesting that HIP-I and huntingtin play a
functional role in the cell filament networks. The HIP1 gene is
ubiquitously expressed in different brain regions at low level. HIP-I is
enriched in human brain but can also be detected in other human tissues as
well as in mouse brain. HIP-I and huntingtin behave almost identically
during subcellular fractionation and both proteins are enriched in the
membrane containing fractions.
相似文献
104.
105.
Duplication of a gene-rich cluster between 16p11.1 and Xq28: a novel pericentromeric-directed mechanism for paralogous genome evolution 总被引:15,自引:6,他引:15
106.
Bardet–Biedl syndrome (BBS) is a rare pediatric ciliopathy characterized by marked clinical variability and extensive genetic heterogeneity. Typical diagnosis of BBS is secured at a median of 9 years of age, and sometimes well into adolescence. Here, we report a patient in whom prenatal detection of increased nuchal fold, enlarged echogenic kidneys, and polydactyly prompted us to screen the most commonly mutated genes in BBS and the phenotypically and genetically overlapping ciliopathy, Meckel–Gruber syndrome (MKS). We identified the common Met390Arg mutation in BBS1 in compound heterozygosity with a novel intronic variant of unknown significance (VUS). Testing of mRNA harvested from primary foreskin fibroblasts obtained shortly after birth revealed the VUS to induce a cryptic splice site, which in turn led to a premature termination and mRNA degradation. To our knowledge, this is the earliest diagnosis of BBS in the absence of other affected individuals in the family, and exemplifies how combining clinical assessment with genetic and timely assays of variant pathogenicity can inform clinical diagnosis and assist with patient management in the prenatal and neonatal setting. 相似文献
107.
108.
While our Y2K worries about old computers “retiring” at midnight captured the television and news media attention, a more significant “old age” phenomenon snuck onto the scene with hardly a headline: the dawn of the age of the aged.1 The over burdened health care system will face a worldwide wave of retirees who will live longer, cost more to treat, and demand new goods and services to help them stay healthy, active, and independent. Research in persuasive technologies and the associated usage of a computing system, device, or application intentionally designed to change a person's attitude or behavior in a predetermined way is showing the potential to assist in improving healthy living, reduce the costs on the health care system, and allow the aged to maintain a more independent life. This article gives a deeper insight into the evolution of persuasive technologies and presents a framework that can guide a researcher or practitioner in comprehending more effectively the work being done in this novel research field. It also provides categories of domains within health care in which these technologies are used and surveys exemplars from published literature. The article's goal is to provide greater understanding by addressing the challenges that lie ahead for all key stakeholders that design and/or use persuasive technologies in health care. 相似文献
109.
Tait D; Riccio M; Sittler A; Scherzinger E; Santi S; Ognibene A; Maraldi NM; Lehrach H; Wanker EE 《Human molecular genetics》1998,7(6):991-997
It has been reported that the ataxin-3 protein containing a polyglutamine
sequence in the pathological range (61-84Q) is localized within the nucleus
of neuronal cells, whereas ataxin-3 with a normal repeat length (12-37Q) is
predominantly a cytoplasmic protein. In this study, the subcellular
localization of the full-length ataxin-3 protein with a glutamine sequence
in the normal range (Q3KQ22) was analysed in two mammalian cell lines.
Using two affinity-purified polyclonal antibodies raised against the N- or
C-terminal portion of ataxin-3, the protein was detected predominantly, but
not exclusively, in the nucleus of COS-7 as well as neuroblastoma cells by
immunofluorescence and confocal laser scanning microscopy (CLSM). The
distribution of the protein in these cellular compartments was confirmed by
biochemical subcellular fractionations. Furthermore, CLSM revealed that the
ataxin- 3 protein present in the nucleus of neuroblastoma cells is
associated with the inner nuclear matrix. Our results taken together with
the finding of a nuclear localization signal in ataxin-3 indicate that the
ataxin-3 protein per se translocates to the nucleus and that an expanded
glutamine repeat is not essential for this transport.
相似文献
110.