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S M Weissman

Publications and source records attributed to S M Weissman.

At least 55 records · Page 3Linked to original sources
PubMed1995

Olfactory receptor-like genes are located in the human major histocompatibility complex.

The murine major histocompatibility complex (MHC) includes sequences that are responsible for haplotype-specific odor types that, in turn, influence mating preference. We report that there are several olfactory receptor genes or pseudogenes in the Class I region of the human MHC. At least one of these genes is intact, appears to encode an mRNA, and is quite homologous to a previously reported murine olfactory receptor.

Amino Acid Sequence↗
PubMed1995

Nonsurgical treatment of open bite in nongrowing patients.

Successful treatment of the adult patient with an open bite dental or skeletal pattern often presents a difficult challenge. While the causes of open bite may be multifactorial in nature, there are specific diagnostic criteria that may allow for an orthodontic treatment modality incorporating extraction therapy with retraction of incisors. Two case presentations illustrate treatment of adult patients with open bites due to proclined incisors. The diagnostic criteria and mechanics for appropriate and successful treatment are discussed. Although the selection of extraction therapy for correction of anterior open bite has a narrow range of application in the overall scheme of open bite treatment, this treatment method has certain areas of application in which success may be anticipated.

Adult↗
PubMed1995

Identification of WASP mutations in patients with Wiskott-Aldrich syndrome and isolated thrombocytopenia reveals allelic heterogeneity at the WAS locus.

Mutation in the gene encoding the recently isolated WASP protein has now been identified as the genetic defect responsible for the X-linked Wiskott-Aldrich syndrome (WAS), a primary immunodeficiency disease associated with extensive phenotypic variability. To elucidate the range of WASP mutations responsible for WAS, we used PCR-SSCP analysis to screen for WASP gene mutation in 19 unrelated boys with the diagnosis of classical or attenuated WAS or isolated thrombocytopenia. All 19 patients had WASP mutations, each of which localized to the initial three or terminal three exons of the gene, and the majority of which were unique in each case. However, a missense mutation which results in substitution of the arginine at WAS codon 86 was identified in three boys with severe WAS as well as in one boy presenting with thrombocytopenia alone. While the three mutations found in the isolated thrombocytopenia patients leave the reading frame intact, about one-half of the gene alterations detected in both severe and attenuated WAS patients result in frameshifted transcript and premature translation termination. These findings therefore confirm the association of WAS with WASP mutation and identify WASP mutation as a cause for isolated congenital thrombocytopenia in males. While the WASP gene defects responsible for isolated thrombocytopenia and other mild presentations of WAS do not appear distinct from those resulting in severe WAS, these data indicate that analysis of WASP gene mutation provides a valuable tool for distinguishing the spectrum of WAS patients and the subset of males with isolated thrombocytopenia who represent mild cases of WAS.

Adolescent↗
PubMed1995

Chromosomal localization and expressed sequence tag generation of clones from a normalized human adult thymus cDNA library.

Expressed sequence tags (ESTs) from 298 clones have been generated from a randomly primed, normalized human adult thymus cDNA library. We describe the chromosomal localization of 136 of these ESTs by PCR-based mapping to a human monochromosomal somatic cell hybrid panel. Data base similarities to known genes are also described. A subset (n = 18) of these randomly primed ESTs extended the sequence of ESTs from other tissues currently in dbEST. Of the nonrepetitive human adult thymus ESTs generated in this study, 237 (79.5%) have no similarity to current data base entries. This would suggest that our collection contains approximately 100 new coding regions from thymus tissue, a large proportion of which likely will represent the middle regions of genes. The mapped ESTs should prove useful as new gene-based markers for mapping and candidate gene hunting, particularly when anchored to a well-developed physical map of the human genome.

Chromosome Mapping↗
PubMed1994

Developmental regulation of human gamma- and beta-globin genes in the absence of the locus control region.

Two lines of transgenic mice carrying a normal 40-kb Kpn I beta-globin cluster transgene lacking the locus control region (LCR) were analyzed for the expression of human gamma- and beta-globin genes during mouse development. After RNase protection assays, the ratios of human G gamma-, A gamma-, or beta-mRNAs relative to endogenous mouse zeta + alpha mRNAs were obtained for each stage of development. The two gamma transgenes were expressed in day-11.5 blood (embryonic stage) and day-13.5 blood (early fetal stage), but their expression was markedly decreased by day 16.5 of fetal life. Expression of the beta transgene was essentially absent at day 13.5, appeared at a low level by day 16.5, and was maximal by day 18.5, reaching a level similar to that observed in adult mice. Therefore, developmentally regulated expression of the human gamma- and beta-globin transgenes was obtained in the absence of the LCR. The relative expression of human gamma- and beta-globin genes was also examined in mice carrying 40-kb Kpn I beta-cluster transgenes with two different base substitutions associated with nondeletion forms of hereditary persistence of fetal hemoglobin (HPFH), -202 C-->G G gamma HPFH and -117 G-->A A gamma HPFH. The ratio of G gamma- to beta-globin transcripts was markedly increased in red blood cells of adult mice from three different lines carrying the transgene with the -202 G gamma HPFH mutation. This result confirms our previous preliminary results (Tanaka et al: Ann NY Acad Sci, 612:167, 1990) indicating that the -202 G gamma HPFH phenotype was reproduced in transgenic mice. The relatively low levels of G gamma-mRNA expression in adult mice carrying the non-HPFH transgene excludes a major influence of the 3' beta-globin enhancer, present upstream of the G gamma gene because of the tandem repeat insertion, as a factor in the persistent G gamma gene expression observed in blood of adult mice carrying the -202 G gamma HPFH transgene. This conclusion is also supported by the fact that, in mice carrying the -117 A gamma HPFH transgene, G gamma-globin mRNA was detected in blood of adult animals only at low levels similar to that observed in the non-HPFH lines. However, the A gamma-HPFH phenotype was not reproduced in the transgenic lines carrying the -117A gamma HPFH mice.

Animals↗
PubMed1994

Construction of libraries enriched for sequence repeats and jumping clones, and hybridization selection for region-specific markers.

We describe a simple and rapid method for constructing small-insert genomic libraries highly enriched for dimeric, trimeric, and tetrameric nucleotide repeat motifs. The approach involves use of DNA inserts recovered by PCR amplification of a small-insert sonicated genomic phage library or by a single-primer PCR amplification of Mbo I-digested and adaptor-ligated genomic DNA. The genomic DNA inserts are heat denatured and hybridized to a biotinylated oligonucleotide. The biotinylated hybrids are retained on a Vectrex-avidin matrix and eluted specifically. The eluate is PCR amplified and cloned. More than 90% of the clones in a library enriched for (CA)n microsatellites with this approach contained clones with inserts containing CA repeats. We have also used this protocol for enrichment of (CAG)n and (AGAT)n sequence repeats and for Not I jumping clones. We have used the enriched libraries with an adaptation of the cDNA selection method to enrich for repeat motifs encoded in yeast artificial chromosomes.

Base Sequence↗
PubMed1994

Isolation and refined regional mapping of expressed sequences from human chromosome 21.

To increase candidate genes from human chromosome 21 for the analysis of Down syndrome and other genetic diseases localized on this chromosome, we have isolated and studied 9 cDNA clones encoded by chromosome 21. For isolating cDNAs, single-copy microclones from a chromosome 21 microdissection library were used in direct screening of various cDNA libraries. Seven of the cDNA clones have been regionally mapped on chromosome 21 using a comprehensive hybrid mapping panel comprising 24 cell hybrids that divide the chromosome into 33 subregions. These cDNA clones with refined mapping positions should be useful for identification and cloning of genes responsible for the specific component phenotypes of Down syndrome and other diseases on chromosome 21, including progressive myoclonus epilepsy in 21q22.3.

Adult↗
PubMed1993

Genes in one megabase of the HLA class I region.

To define the gene content of the HLA class I region, cDNA selection was applied to three overlapping yeast artificial chromosomes (YACs) that spanned 1 megabase (Mb) of this region of the human major histocompatibility complex. These YACs extended from the region centromeric to HLA-E to the region telomeric to HLA-F. In addition to the recognized class I genes and pseudogenes and the anonymous non-class-I genes described recently by us and others, 20 additional anonymous cDNA clones were identified from this 1-Mb region. We also identified a long repetitive DNA element in the region between HLA-B and HLA-E. Homologues of this element were located at several sites in the human genome outside of the HLA complex. The portion of the HLA class I region represented by these YACs shows an average gene density as high as the class II and class III regions. Thus, the high gene density portion of the HLA complex is extended to more than 3 Mb.

Animals↗
PubMed1993

Differential expression of four members of the POU family of proteins in activated and phorbol 12-myristate 13-acetate-treated Jurkat T cells.

The POU family of proteins binds specifically to octamer DNA motifs present in the promoters of several genes and regulates their expression. We identified the presence of four members of the POU family of proteins, Oct-1, Oct-2, Oct-T1, and Oct-T2, in the human T-cell line Jurkat. To obtain insight into the physiological role played by these proteins in T cells, we studied the time course of expression of these genes in resting, activated, and phorbol 12-myristate 13-acetate (PMA)-treated cells. The expression of the gene encoding Oct-1 (now assigned the name OTF1 for octamer-binding transcription factor 1) remained unchanged and the levels of Oct-T2 mRNA decreased with increasing time of incubation to undetectable amounts in all three states of T-cell growth. The levels of Oct-2 mRNA and protein were increased in activated cells, were increased to a lesser extent in the PMA-treated cells, and were undetectable in resting cells. The levels of the Oct-T1 transcripts increased dramatically in PMA-treated cells but not in resting or activated cells. Sequence analysis of the Oct-T1 cDNA showed an open reading frame coding for a POU domain-containing protein of 42.7 kDa. Transient transfection of the gene encoding Oct-T1 decreased the activity of the interleukin 2 gene promoter in activated Jurkat cells. Further, there is evidence for an additional octamer-binding protein, Oct-T3, in Jurkat T cells.

Amino Acid Sequence↗
PubMed1993

Evaluation of the contingent replication assay (CRA) and its application to the study of the general transcription initiation factor, TFIIF.

The Contingent replication assay (CRA) is a rapid assay for the screening and isolation of cDNAs by protein-protein or protein-DNA interactions in mammalian cells. The method has been shown to enrich a plasmid containing a cDNA encoding the bacterial replication-related protein, R6K, from a mixture of two plasmids. In this report we present data illustrating the sensitivity and selectivity of the method. Using the small subunit of TFIIF (Rap30) as a target, we demonstrate the enrichment of a clone encoding the large subunit, Rap74, from a cDNA library. Additional cDNA clones including human Rap30 and an anonymous cDNA clone homologous to members of the human cdc2 kinase family were enriched and isolated by a modified screening approach. The structure of these additional clones suggest that the CRA enriches for products that interact not only directly with the target protein but also through bridging by endogenous proteins.

Animals↗
PubMed1993

Screening for in vivo protein-protein interactions.

We describe an in vivo approach for the isolation of proteins interacting with a protein of interest. The protein of interest is "tagged" with a portion of the biotin carboxylase carrier protein (BCCP), encoded on a specially constructed plasmid, so that it becomes biotinylated in vivo. The "query" proteins (e.g., those in a cDNA library) are tagged by fusing them to the 3' end of the lacZ gene on a lambda vector in such a way that the beta-galactosidase activity is not disrupted. These phage are transfected into cells containing the plasmid encoding the BCCP-tagged protein. The infection lyses the cells and exposes the protein complexes. The BCCP-tagged protein and any associated protein(s) are "captured" by using avidin, streptavidin, or anti-biotin antibody-coated filters. The detection of bound protein is accomplished by directly assaying for beta-galactosidase activity on the filters. Positive plaques can be plaque-purified for DNA sequencing. We have tested this approach by using c-Fos and c-Jun as our model system. We show that avidin, streptavidin, or polyclonal anti-biotin (but not a monoclonal anti-biotin) antibody is capable of specifically capturing in vivo biotinylated beta-galactosidase and c-Jun and that this capture is dependent upon the presence of both avidin and the BCCP moiety. Further, complexes containing c-Jun and c-Fos can also be isolated in this manner, and the isolation of this complex is dependent on the presence of c-Fos, c-Jun, avidin, and the BCCP moiety. We discuss the possible uses and limitations of this technique for isolating proteins that interact with a known protein.

Acetyl-CoA Carboxylase↗
PubMed1993

Domain structure of a human general transcription initiation factor, TFIIF.

The structural and functional domains of a general transcription initiation factor, TFIIF (RAP30/74, FC), have been investigated using various deletion mutants of each subunit, both in vivo and in vitro. An in vivo assay showed that the N-terminal sequence containing residues of 1-110 of RAP30 that is located close to a sigma homology region interacts with a minimum sequence of residues 62-171 of RAP74 to form a heteromeric interaction. Reconstitution of in vitro transcription activity by deletion mutants of RAP74 clearly indicated that both N-terminal residues 73-205 and C-terminal residues 356-517 are essential for full activity, the former interacting with RAP30, thus complexing with RNA polymerase II. From these data, the functional significance of domain structure of TFIIF is discussed in terms of its sigma homology sequences and complex formation with RNA polymerase II in the initiation and elongation of transcription.

Amino Acid Sequence↗
PubMed1993

Assignment of the human GTF2F1 gene to chromosome 19p13.3.

TFIIF (also termed FC) is a general transcription initiation factor that binds to RNA polymerase II and recruits it to a promoter. TFIIF is a heterodimer composed of 74-kDa (RAP74; gene symbol GTF2F1) and 30-kDa (RAP30; gene symbol GTF2F2) subunits. Here we report the mapping of the human GTF2F1 gene to band 19p13.3. Localization was performed by fluorescence in situ hybridization using the human RAP74 genomic cosmid clone as the probe.

Chromosome Banding↗
PubMed1993

Application of cDNA selection techniques to regions of the human MHC.

Identification of transcribed sequences by cDNA selection is a potentially rapid and efficient way of scanning large genomic DNA fragments for the presence of genes. To evaluate this approach further, we have applied it to three yeast artificial chromosomes (YACs) and examined the products obtained from a total of about 1100 kb from two regions of the human major histocompatibility complex (MHC). One YAC was derived from an extensively studied portion of the Class II region of the MHC. The cDNAs recovered from this YAC included representatives of the previously described genes as well as one or more cDNA clones not described in the databases. A second YAC spanned about 330 kb of DNA surrounding the Class I gene HLA-A. In addition to Class I clones, 10 distinct cDNA products were identified from this YAC. A third YAC contained about 700 kb of human DNA, including 260 kb of overlap with the second YAC, and recovered an additional cDNA complementary to YAC B30 H3 DNA. Overall, the method is shown to be able to detect very scarce cDNAs and to detect a large fraction of coding sequences in YAC clones. Advantages and limitations of the approach are discussed.

Chromosome Mapping↗
PubMed1993

Diagnosis and treatment planning of hypodivergent skeletal pattern with clockwise occlusal plane rotation.

Diagnostic treatment planning of Class III malocclusion is complicated due to the interaction of development, timing, dental pattern, and skeletal relationships. Historically, the treatment of adult Class III malocclusions has tended to be seen primarily as cases of mandibular prognathism. As diagnostic acumen and surgical skills improve and merge, orthodontic and surgical treatment plans for Class III malocclusions have become more common. Class III malocclusions now tend to be described in terms of mandibular prognathism, horizontal maxillary hypoplasia, maxillary vertical hypoplasia, and mandibular dentoalveolar retrusion. The purpose of this paper is to present a combined surgical-orthodontic treatment approach involving clockwise rotation of the occlusal plane for treatment of hypodivergent Class III skeletal pattern and dental malocclusion.

Adult↗
PubMed1992

Gene therapy.

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Animals↗