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11p15.5 is an important tumor-suppressor gene region, showing loss of heterozygosity in Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. We previously mapped directly by genetic complementation a subtransferable fragment (STF) harboring an embryonal tumor-suppressor gene and spanning about 2.5 Mb. We have now mapped the centromeric end of this STF between...
We describe a tool for analyzing and annotating large genomic sequences containing introns. The analysis and annotation tool (AAT) includes two sets of programs, one for comparing the query sequence with a protein database and the other for comparing the query with a cDNA database. Each set contains a fast database search program and a rigorous alignment program. The database search program quickly...
Cytogenetic studies of banded chromosomes and fluorescencein situhybridization (FISH) of several yeast artificial chromosomes (YACs) that are part of a 128-kb resolution physical map of a portion of 12q13 revealed that 4/14 (28%) lipomas have breakpoints in 12q13. These breakpoints are more than 10 Mb away from theHMGICgene at 12q14–q15, which is known to be modified in some lipomas. FISH with individual...
We have hybridized all 28 chromosome-specific painting probes from the domestic sheep (Ovis aries,2n= 54) onto metaphase chromsomes of the Indian muntjac deer (Muntiacus muntjak vaginalis,2n= 6,7) and identified 35 conserved chromosomal segments. Results from this study show that most of the sheep acrocentric chromosomes hybridized to single regions in the Indian muntjac genome. This conserved hybridization...
Deletions at chromosome 11q23 are frequent events in a variety of human neoplasms, including breast, lung, and ovarian carcinomas. Two common regions of loss of heterozygosity, shared between lung and breast carcinomas, have been previously identified at 11q23, suggesting that the same tumor susceptibility genes are altered in these two malignancies. One of these regions, refined in lung adenocarcinoma,...
The Gbx2 homeodomain is widely conserved in metazoans. We investigated the mouseGbx2locus by isolation and characterization of genomic clones and by physical localization to the genome. TheGbx2gene contained a single intron that separated the proposed functional protein domains. This organization was conserved with humanGBX2.Physical localization ofGbx2to Chromosome 1C5–E1 indicated that the genomic...
The inherited metabolic disorder trimethylaminuria (fish-odor syndrome) is associated with defective hepaticN-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase (FMO). AsFMO3encodes the major form of FMO expressed in adult human liver, it represents the best candidate gene for the disorder. The structural organization ofFMO3was determined by sequencing the products...
We have isolated a novel cDNA (SEL1L) that shows sequence similarities to SEL-1, a gene identified as an extragenic suppressor of thelin-12hypomorphic mutant fromCaenorhabditis elegans(7, 8). SEL1L exhibits a tissue-specific pattern of expression: a single poly(A) + RNA species of 7.5 kb is abundantly expressed only in the pancreas of healthy individuals, whereas low to undetectable levels...
We constructed and screened a human fetal cochlear cDNA library to identify genes involved in hearing and deafness. From this library we isolated a cDNA corresponding to the highly conserved ancient gene antiquitin (ATQ1). The plant homolog ofATQ1is thought to be involved in regulating turgor pressure, a function that also would be essential for cells of the mammalian cochlea. Northern blots of 13...
Microphthalmia with linear skin defects syndrome (MLS) is an X-linked dominant, male-lethal disorder associated with chromosomal rearrangements that result in deletions of the distal short arm of the X chromosome. In an effort to isolate expressed sequences from the 500-kb MLS critical region in Xp22.3, exons were trapped from 14 overlapping cosmids. Using exon connection followed by cDNA library...
LIM domains, found in over 60 proteins, play key roles in the regulation of developmental pathways. They were first identified as cysteine-rich motifs found in the three proteins Lin-11, Isl-1, and Mec-3. LIM proteins frequently contain DNA-binding homeodomains, allowing these proteins to activate transcription. LIM domains also function as protein-binding interfaces, mediating specific protein–protein...
A putative tumor suppressor gene involved in B cell chronic lymphocytic leukemia (B-CLL) was mapped to human chromosome 13q14.3 close to the genetic markers D13S25 and D13S319. We constructed a 780-kb-long contig composed of cosmids, bacterial artificial chromosomes, and bacteriophage P1-derived artificial chromosomes that provides essential information and tools for the positional cloning of this...
Reelin is the protein defective inreelermice, an extensively studied model of brain development. Thereelingene (symbolReln) codes for a protein of the extracellular matrix that contains eight successive repeats of 350 to 390 amino acids. In this work, we describe the genomic structure of the mousereelingene and the 5′-flanking genomic DNA sequences. Thereelingene is composed of 65 exons spread over...
Orc5p is a subunit of the origin recognition complex in the budding yeastSaccharomyces cerevisiae,which has been shown to play a critical role in both chromosomal DNA replication and transcriptional silencing. We have cloned cDNAs from both human and fission yeastSchizosaccharomyces pombethat encode proteins homologous to the budding yeast andDrosophilaOrc5p. Human Orc5p showed 35.1, 22.3, and 19...
The expansion of a (CAG) n trinucleotide repeat has been associated with at least eight neurological disorders in which the repeats code for polyglutamine in the protein. To identify additional genes that possess (CAG) n repeats, single-stranded cDNA clones derived from adult human brain were screened using biotinylated oligonucleotide (CAG) 8 , and the hybridizing complexes...
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