ABSTRACT
Endometriosis is a female disorder characterized by the presence of uterine endometrial tissue in ectopic loci. Previous studies reported a higher prevalence of particular human leukocyte antigen (HLA) in endometriosis. In order to confirm the association between endometriosis and the HLA region, 15 polymorphic microsatellite markers distributed in the HLA class II to class III region were subjected to association analysis by polymerase chain reaction (PCR)-based DNA typing of 89 patients and 136 healthy controls. Statistical analysis of the allelic frequency at each microsatellite locus showed that there were no statistically significant differences in the allele frequency distributions between the cases and controls. This finding suggests that the etiology of endometriosis does not involve the HLA class II genomic region and a portion of class III genomic region in the Japanese population.
Subject(s)
Endometriosis/genetics , Genes, MHC Class II , Genetic Predisposition to Disease , HLA Antigens/genetics , Uterine Diseases/genetics , Adult , Asian People , Female , Gene Frequency , Genetic Association Studies , Humans , Microsatellite Repeats , Middle Aged , Polymorphism, GeneticSubject(s)
GTP-Binding Proteins/genetics , H-2 Antigens/genetics , Major Histocompatibility Complex , Animals , Base Sequence , Blotting, Northern , Centromere , Chromosome Mapping , Cloning, Molecular , DNA, Complementary , GTP-Binding Proteins/chemistry , Humans , Mice , Molecular Sequence Data , U937 Cells , rap GTP-Binding ProteinsABSTRACT
Tctex3 showing restricted expression in male germ cells has been isolated during the process of chromosome walking in the mouse t-complex region. The total sequence of Tctex3 cDNA predicts a protein of 580 amino acids with two C4HC3 type PHD fingers. The region containing this conserved motif is shared among members of the Polycomblike proteins that include the mouse M96 and Drosophila Polycomblike. A partial cDNA for a human homolog of Tctex3, HUTEX3, has also been isolated. Mouse Tctex3 gene was mapped adjacent to Tsc2 gene on mouse Chromosome (Chr) 17, and HUTEX3 was located closely to HSET gene in the HLA class II region of chromosome 6.
Subject(s)
Drosophila Proteins , Intracellular Signaling Peptides and Proteins , Microtubule-Associated Proteins , Nuclear Proteins/biosynthesis , Testis/metabolism , Amino Acid Sequence , Animals , Base Sequence , Chromosome Mapping , Chromosomes, Human, Pair 6 , DNA-Binding Proteins , Drosophila melanogaster , Humans , Male , Mice , Molecular Sequence Data , Nuclear Proteins/genetics , Polycomb-Group Proteins , Rats , Repressor Proteins/analysis , Repressor Proteins/genetics , Transcription Factors , Ubiquitin-Protein Ligases , Xenopus laevis , t-Complex Genome RegionABSTRACT
A cosmid contig was constructed from a YAC clone with a 220-kb insert that spans the centromeric side of the human MHC class II region, corresponding to the mouse t complex. The gene order was identified to be HSET-HKE1.5-HKE2-HKE3-RING1-HKE6- HKE4 (RING5). The genomic sequence of a 42,801-bp long region encoded by one cosmid clone in the RING1, HKE6, and HKE4 subregions was determined by the shotgun method. The exon-intron organization of these three genes, RING1 (Ring finger protein), HKE6 (steroid dehydrogenase-like protein), and HKE4 (transmembrane protein with histidine-rich charge clusters), was determined. The previously reported RING2 gene was revealed to be identical to HKE6. Transcripts from HKE4 were detected in the placenta, lung, kidney, and pancreas. Those of HKE6 were found in the liver and pancreas. The 25-kb region proximal to the RING1 gene includes an extensive dense cluster of Alu repeats (about 1.2 Alu per kb), and no gene has been identified in this so far. The region is equivalent to part of the mouse t complex and could be of relevance to human development.
Subject(s)
DNA-Binding Proteins/genetics , HLA-DP Antigens/genetics , Membrane Proteins/genetics , Multigene Family , Oxidoreductases , Proteins/genetics , Sequence Analysis, DNA , Amino Acid Sequence , Base Sequence , Blotting, Northern , Cation Transport Proteins , Centromere , Cloning, Molecular , Cosmids , DNA, Complementary , Humans , Molecular Sequence Data , Polycomb Repressive Complex 1 , Restriction MappingABSTRACT
To elucidate the detailed gene organization of the human leukocyte antigen (HLA) class I region on chromosome 6, seven contiguous cosmid genomic clones covering the 237-kb segment around the HLA-B and -C loci were subjected to DNA sequencing by the shotgun strategy to give a single contig of 236,822 bp from the MICA gene (58.2 kb centromeric of HLA-B) to 90.8 kb telomeric of HLA-C. This region was confirmed to contain four known genes, MICA, HLA-17, HLA-B, and HLA-C, from centromere to telomere. Further, a new member of the P5 multicopy genes was found to be about 1.3 kb upstream of the HLA-17 gene and designated P5.8. Five novel genes designated NOB1-5 were identified by RT-PCR and Northern blot hybridization. In addition, two pseudogenes, dihydrofolate reductase pseudogene (DHFRP) and ribosomal protein L3 homologous gene (RPL3-Hom), were also found in the vicinity of the HLA-B and -C genes, respectively. The two segments (about 40 kb) downstream of the HLA-B and HLA-C genes showed high sequence homology to each other, suggesting that segmental genome duplication including the major histocompatibility complex (MHC) class I gene must have occurred during the evolution of the MHC.
Subject(s)
HLA-B Antigens/genetics , HLA-C Antigens/genetics , Blotting, Northern , Chromosomes, Artificial, Yeast/genetics , Chromosomes, Human, Pair 6/genetics , Cloning, Molecular , Cosmids , DNA/genetics , Evolution, Molecular , Humans , Molecular Sequence Data , Multigene Family , Polymerase Chain Reaction , RNA, Messenger/genetics , RNA, Messenger/metabolism , Restriction Mapping , Ribosomal Protein L3 , Sequence Analysis, DNA , Sequence Homology, Nucleic Acid , Tissue DistributionABSTRACT
cDNA clones corresponding to the HKE4 and HKE6 genes at the centromeric end of the HLA region on human chromosome 6p21.3 were isolated and characterized. The predicted amino acid sequences of HKE4 and HKE6 exhibited 81.5 and 85.6% identity to the mouse homologues, Ke4 and Ke6, respectively. HKE4 may encode a membrane protein with histidine-rich charge clusters. HKE6 possesses remarkable amino acid sequence conservation with several bacterial proteins with oxidoreductase function and also shows significant homology with the two unique functional domains containing the nucleotide cofactor binding site and the consensus motif characteristic of the members of the superfamily of short-chain alcohol dehydrogenases such as human and rat steroid and prostaglandin dehydrogenases.
Subject(s)
Chromosomes, Human, Pair 6 , HLA Antigens/genetics , Membrane Proteins/genetics , Oxidoreductases , Proteins/genetics , Amino Acid Sequence , Animals , Base Sequence , Cation Transport Proteins , Cell Line , Centromere , Cloning, Molecular , DNA, Complementary , Gene Dosage , Histocompatibility Antigens/genetics , Humans , Mice , Molecular Sequence Data , Sequence Homology, Amino AcidABSTRACT
We previously reported the presence of a new gene (HSET) with an unknown function, in the centromeric side of the class II gene region of the human major histocompatibility complex (MHC). cDNA clones corresponding to the HSET gene were isolated from a human testis cDNA library. A 2.4 kilobase transcript from the HSET gene was abundantly expressed in testis, B-cell, T-cell, and ovary cell lines but was not detected in lung or stomach. Analysis of the nucleotide sequence of the HSET cDNA clones revealed significant similarity to kinesin-related proteins in yeast, Drosophila, and human. Its predicted amino acid sequence contains a domain with strong sequence similarity to the ATP-binding and motor domains of a plus end-directed microtubule motor protein, kinesin, which might be involved in mitotic chromosome segregation, suggesting that the HSET gene encodes a novel kinesin-related protein.
