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  • 1
    Digitale Medien
    Digitale Medien
    The P5 multicopy gene family in the MHC is related in sequence to human endogenous retroviruses HERV-L and HERV-16 (1999)
    Springer
    Immunogenetics 49 (1999), S. 404-412 
    Details
    ISSN: 1432-1211
    Schlagwort(e): Key words P5 multicopy gene family ; Human endogenous retrovirus ; Major histocompatibility complex ; RepeatMasker ; Retroelements
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract  P5 is believed to be a multicopy gene family with at least eight members restricted to the major histocompatibility complex (MHC). Although the function of P5 genes is not known, one of the family members, P5-1, was found previously to be specifically transcribed in lymphoid cells and tissue. In this study, we used computer programs Censor and RepeatMasker, and dot plot analysis to show that the major P5 family members are related in sequence to human endogenous retroviruses, HERV-L and HERV-16. The P5-HERV sequences have at least 60% sequence identity with HERV-L within the pol region but differ significantly within the gag and LTR regions. The LTRs flanking the P5-HERV sequences share about 70% identity with the repeat element LTR16B. Structural analysis of open reading frames (ORFs) confirmed that the P5-1 cDNA is characterized by many stop codons and short putative coding regions resembling the patterns found in the HERV-L nucleotide sequence rather than those found in an mRNA sequence such as expressed by HLA class I genes. A 159 base pair (bp) ORF at the 5' end of the 2535 bp P5-1 mRNA may code for a peptide of 52 amino acids with a domain identical in sequence to the signal peptide of HLA molecules. Furthermore, the P5-1 mRNA is complementary in sequence to retroviral pol mRNA. Therefore, the P5-1 genomic sequence appears to be an example of an HERV within the MHC that expresses an antisense transcript with a possible role in immunity to retrovirus infection.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002510050513
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  • 2
    Digitale Medien
    Digitale Medien
    Immunological effects of cancer chemotherapy in malignant melanoma (1978)
    Springer
    Cancer immunology immunotherapy 4 (1978), S. 185-192 
    Details
    ISSN: 1432-0851
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The effects on the immune system of highdose cyclical combination chemotherapy were studied in nine patients with advanced malignant melanoma. Chemotherapy consisted of monthly cycles of dimethyl triazeno imidazole carboxamide 150 mg/m2 i.v. daily from days 1–5, cyclophosphamide 1000 mg/m2 i.v. on day 5, and vincristine 1.4 mg/m2 i.v. on day 5. Immunological testing was carried out prior to treatment and at weekly intervals during the first month. B, T and non-B, non-T cell numbers all tended to fall early in the cycle as did the phytohaemagglutinin(PHA)-induced transformation and PHA-induced cytotoxicity to chicken red cells. Although PHA-induced transformation and cytotoxicity usually returned to normal by day 29, B and T cell numbers often remained subnormal. In contrast, levels for antibody-dependent, cell-mediated cytotoxicity (ADCC) were relatively stable throughout the cycle. Two patients with subsequent tumour response to therapy had rebound supranormal PHA transformations between weeks 1 and 3 of the first cycle. No other changes correlated with prognosis in individual patients. Analysis of the temporal relationships between PHA transformation, PHA-induced cytotoxicity, and ADCC supported the concept that the three assays reflect the function of separate mononuclear cell subpopulations. The stability of ADCC is of particular interest in view of other work suggesting that this function may be important in immune responses to tumours, including melanoma.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00204738
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  • 3
    Digitale Medien
    Digitale Medien
    Duplication and Diversification of the Apolipoprotein CI (APOCI) Genomic Segment in Association with Retroelements (2000)
    Springer
    Journal of molecular evolution 50 (2000), S. 391-396 
    Details
    ISSN: 1432-1432
    Schlagwort(e): Key words: Apolipoprotein CI — Hepatic control region — Duplication — Alu — Retroelements — Diversity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract. We have previously shown that several multicopy gene families within the major histocompatibility complex (MHC) arose from a process of segmental duplication. It has also been observed that retroelements play a role in generating diversity within these duplicated segments. The objective of this study was to compare the genomic organization of a gene duplication within another multicopy gene family outside the MHC. Using new continuous genomic sequence encompassing the APOE-CII gene cluster, we show that APOCI and its pseudogene, APOCI′, are contained within large duplicated segments which include sequences from the hepatic control region (HCR). Flanking Alu sequences are observed at both ends of the duplicated unit, suggesting a possible role in the integration of these segments. As observed previously within the MHC, the major differences between the segments are the insertion of sequences (approximately 200–1000 bp in length), consisting predominantly of Alu sequences. Ancestral retroelements also contribute to the generation of sequence diversity between the segments, especially within the 3′ poly(A) tract of Alu sequences. The exonic and regulatory sequences of the APOCI and HCR loci show limited sequence diversity, with exon 3 being an exception. Finally, the typing of pre- and postduplication Alus from both segments indicates an estimated time of duplication of approximately 37 million years ago (mya), some time prior to the separation of Old and New World monkeys.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002399910042
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  • 4
    Digitale Medien
    Digitale Medien
    The Evolution of MHC Diversity by Segmental Duplication and Transposition of Retroelements (1997)
    Springer
    Journal of molecular evolution 45 (1997), S. 599-609 
    Details
    ISSN: 1432-1432
    Schlagwort(e): Key words: Retroelements — Segmental duplication — MHC — Diversity — Alu
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract. Sequence analysis of a 237 kb genomic fragment from the central region of the MHC has revealed that the HLA-B and HLA-C genes are contained within duplicated segments peri-B (53 kb) and peri-C (48 kb), respectively, and separated by an intervening sequence (IF) of 30 kb. The peri-B and peri-C segments share at least 90% sequence homology except when interrupted by insertions/deletions including Alu, L1, an endogenous retrovirus, and pseudogenes. The sequences of peri-B, IF, and peri-C were searched for the presence of Alu elements to use as markers of evolution, chromosomal rearrangements, and polymorphism. Of 29 Alu elements, 14 were identified in peri-B, 11 in peri-C, and 4 in IF. The Alu elements in peri-B and peri-C clustered phylogenetically into two clades which were classified as ``preduplication'' and ``postduplication'' clades. Four Alu J elements that are shared by peri-B and peri-C and are flanked by homologous sequences in their paralogous locations, respectively, clustered into a ``preduplication'' clade. By contrast, the majority of Alu elements, which are unique to either peri-B or peri-C, clustered into a postduplication clade together with the Alu consensus subfamily members ranging from platyrrhine-specific (Spqxcg) to catarrhine-specific Alu sequences (Y). The insertion of platyrrhine-specific Alu elements in postduplication locations of peri-B and peri-C implies that these two segments are the products of a duplication which occurred in primates prior to the divergence of the New World primate from the human lineage (35–44 mya). Examination of the paralogous Alu integration sites revealed that 9 of 14 postduplication Alu sequences have produced microsatellites of different length and sequence within the Alu 3′-poly A tail. The present analysis supports the hypothesis that HLA-B and HLA-C genes are products of an extended segmental duplication between 44 and 81 million years ago (mya), and that subsequent diversification of both genomic segments occurred because of the mobility and mutation of retroelements such as Alu repeats.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/PL00006264
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  • 5
    Digitale Medien
    Digitale Medien
    The Major Histocompatability Complex (MHC) Contains Conserved Polymorphic Genomic Sequences That Are Shuffled by Recombination to Form Ethnic-Specific Haplotypes (1997)
    Springer
    Journal of molecular evolution 45 (1997), S. 17 -23 
    Details
    ISSN: 1432-1432
    Schlagwort(e): Key words: Polymorphism — Recombination — Ancestral haplotypes — Major histocompatibility complex —Homo sapiens
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract. The major histocompatibility complex (MHC) consists of polymorphic frozen blocks (PFBs) that are linked to form megabase haplotypes. These blocks consist of polymorphic sequences and define regions where recombination appears to be inhibited. We have been able to show, using a highly polymorphic sequence centromeric of HLA-B (within the beta block), that PFBs are conserved and contain specific insertions/deletions and substitutions that are the same for individuals with the same MHC haplotype but that differ between at least most different haplotypes. A sequence comparison between ethnic-specific haplotypes shows that these sequences have remained stable and predate the formation of these haplotypes. To determine whether the same conserved block has been involved in the generation of multiple haplotypes, we compared the block typing profiles of different ethnic specific haplotypes. Block typing profiles have previously been shown to be identical in individuals with the same MHC haplotype but, generally, to differ between different haplotypes. It was found that some PFBs are common to more than one haplotype, implying a common ancestry. Subsequently, haplotypes have been generated by the shuffling and exchange of these PFBs. The regions between these PFBs appear to permit the recombination sites and therefore could be expected to exhibit either low polymorphism or a localized ``hotspot.''
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/PL00006194
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  • 6
    Digitale Medien
    Digitale Medien
    Coevolution of HLA-B and PERB11.1 (MICA): Significance of Independent Triplet Expansion Within the Transmembrane Region of PERB11.1 (MICA) (2000)
    Springer
    Journal of molecular evolution 50 (2000), S. 359-365 
    Details
    ISSN: 1432-1432
    Schlagwort(e): Key words: PERB11.1 — MICA — Nomenclature — Putative lineage — Polymorphism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract. Several highly polymorphic sequences are present in the beta block of the MHC, especially HLA-B, HLA-C, PERB11.1 (MICA), and PERB11.2 (MICB). It is now apparent that the polymorphism of PERB11.1 is of the same order as that of HLA-A, -B, and -C and it has been suggested that PERB11 could explain some of the disease associations previously attributed to HLA-B. Phylogenetic analysis of PERB11 α-domain sequences demonstrates relationships with HLA-B cross-reactive serogroups. In contrast, the transmembrane polymorphisms do not appear to be associated with either PERB11 or HLA-B. These data indicate that PERB11 and HLA-B have evolved in concert from their common ancestors and that the transmembrane polymorphisms have arisen independently and more recently. MHC disease associations will need to be reviewed in the light of mechanisms such as receptor binding and signaling.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002399910039
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  • 7
    Digitale Medien
    Digitale Medien
    Genomic Characterization of the Region Between HLA-B and TNF: Implications for the Evolution of Multicopy Gene Families (1997)
    Springer
    Journal of molecular evolution 44 (1997), S. S147 
    Details
    ISSN: 1432-1432
    Schlagwort(e): Key words: HLA-B — TNF — Multicopy gene families
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract. The major histocompatibility complex (MHC) contains genes which confer susceptibility to numerous diseases and must be important in primate evolution. In some instances, genes have been mapped to the region between human histocompatibility leukocyte antigen (HLA)-B and tumor necrosis factor (TNF) but precise localization has proven difficult especially since this region is subject to insertions, deletions, and duplications. Utilizing computer similarity searches and coding prediction programs, we have identified several potential coding sequences between HLA-B and TNF. Three of these sequences, PERB11.2, PERB15, and PERB18, are similar to members of multicopy gene families that are located in other regions of the MHC. The identification of numerous fragmented and intact retroelements (L1, Alu, LTR, and THE sequences) flanking the PERB11 and PERB15 genes suggests that these retroelements are involved in the duplication process. The evaluation of candidate genes for disease susceptibility within the MHC is complicated by their similarity to other members of multicopy gene families. The determination of sequence differences within and between species provides a strategy with which to investigate the candidate genes between HLA-B and TNF.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/PL00000064
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  • 8
    Digitale Medien
    Digitale Medien
    The Evolution of MHC Diversity by Segmental Duplication and Transposition of Retroelements (1998)
    Springer
    Journal of molecular evolution 46 (1998), S. 734-734 
    Details
    ISSN: 1432-1432
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/PL00006355
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  • 9
    Digitale Medien
    Digitale Medien
    Using Alu J Elements as Molecular Clocks to Trace the Evolutionary Relationships Between Duplicated HLA Class I Genomic Segments (2000)
    Springer
    Journal of molecular evolution 50 (2000), S. 510-519 
    Details
    ISSN: 1432-1432
    Schlagwort(e): Key words: HLA class I region — Genomic organization — Duplications — Alu J retroelements
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract. The class I region of the major histocompatibility complex contains two subgenomic blocks (250–350 kb each), known as the alpha and beta blocks. These blocks contain members of multicopy gene families including HLA class I, HERV-16 (previously called P5 sequences), and PERB11 (MIC). We have previously shown that each block consists of imperfect duplicated segments (duplicons) containing linked members of different gene families, retroelements and transposons that have coevolved as part of two separate evolutionary events. Another region provisionally designated here as the kappa block is located between the alpha and the beta blocks and contains HLA-E, -30, and -92, HERV-16 (P5.3), and PERB11.3 (MICC) within about 250 kb of sequence. Using Alu elements to trace the evolutionary relationships between different class I duplicons, we have found that (a) the kappa block contains paralogous (duplicated) Alu J sequences and other retroelement patterns more in common with the beta than the alpha block; (b) the retroelement pattern associated with the HLA-E duplicon is different from all other HLA class I duplicons, indicating a more complex evolution; (c) the HLA-92 duplicon, although substantially shorter, is closely related in sequence to the HLA-B and -C duplicons; (d) two of the six paralogous Alu J elements within the HLA-B and -C duplicons are associated with the HLA-X duplicon, confirming their evolutionary relationships within the beta block; and (e) the paralogous Alu J elements within the alpha block are distinctly different from those identified within the beta and kappa blocks. The sequence conservation and location of duplicated (paralogous) Alu J elements in the MHC class I region show that the beta and kappa blocks have evolved separately from the alpha block beginning at a time before or during the evolution of Alu J elements in primates.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002390010054
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  • 10
    Digitale Medien
    Digitale Medien
    Comparison Between Two Human Endogenous Retrovirus (HERV)-Rich Regions Within the Major Histocompatibility Complex (1999)
    Springer
    Journal of molecular evolution 48 (1999), S. 675-683 
    Details
    ISSN: 1432-1432
    Schlagwort(e): Key words: Human endogenous retrovirus — Duplications — Multicopy genes — Major histocompatibility complex
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract. Sixteen human endogenous retrovirus (HERV) sequences were detected within 656 kb of genomic sequence obtained from the alpha- and beta-block of the class I region of the major histocompatibility complex (MHC). The HERVs were identified and characterized as family members of HERV-16 (11 copies), HERV-L (1 copy), HERV-I (2 copies), HERV-K91 (1 copy), and HARLEQUIN (1 copy) by sequence comparison using CENSOR or Repeat Masker, BLAST searches, and dot plots. The 11 copies of HERV-16 arose as products of duplication of genomic segments containing HLA class I (HLAcI) and PERB11 (MIC) genes inter alia, whereas the other five HERVs arose after duplication probably as a consequence of single insertion events or translocations. HERV-L and HERV-I are located between the duplicated genes PERB11.2 (MICB) and PERB11.1 (MICA), and HLA-B and HLA-C, respectively, whereas HERV-K91 and HARLEQUIN are located telomeric of HLA-C. A highly fragmented copy of HERV-I was also found telomeric of PERB11.4. Structural analysis of open reading frames (ORFs) revealed the absence of intact coding sequence within the putative gag, pol, and env gene regions of all the HERVs with the exception of HERV-K91, which had two large ORFs within the region of the putative protease and pol genes. In addition, the 5′-LTR of HERV-L contained a 2.5-kb element that was AT-rich and large ORFs with putative amino acid sequences rich in tyrosines and isoleucines. HERV-I, HARLEQUIN, and at least four copies of HERV-16 appear to have been receptors for the insertion of other retrotransposons including Alu elements and fragments of L1 and THE1. Examination of flanking sequences suggests that HERV-I and HERV-L had occurred by insertion into ancient L1 fragments. This study has revealed that the alpha- and beta-block region within the MHC is rich in HERV sequences occurring at a much higher ratio (10 to 1) than normally observed in the human genome. These HERV sequences will therefore enhance further studies on disease associations and differences between human haplotypes and primates and their role in the evolution of class I genes in the MHC.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/PL00006511
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