Evolutionary Dynamics of Non-coding Sequences Within the Class II Region of the Human MHC

Beck, Stephan; Abdulla, Sarah; Alderton, Robert P.; Glynne, R; Gut, I.G.; Hosking, L. K.; Jackson, Amanda; Kelly, Anita M.; Newell, William R.; Sanséau, Philippe; Radley, Elizabeth; Thorpe, Karen L.; Trowsdale, John

doi:10.1006/jmbi.1996.0001

Cited by 77 publications

(35 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Alu repeats are known to recruit regulatory proteins (28,50), and these particular forms of Alu are twice as abundant in the LMP/TAP region as compared with the genome average (51). Furthermore, analysis of the human genome sequence reveals preferential retention of Alu repeats in G ϩ C-rich (gene-rich) regions, suggesting a role for these repeats in gene expression (52).…”

Section: Discussionmentioning

confidence: 99%

Recruitment of Heterogeneous Nuclear Ribonucleoprotein A1in Vivo to the LMP/TAP Region of the Major Histocompatibility Complex

Donev

Horton

Beck

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Sequences containing the matrix recognition signature were identified adjacent to the LMP/TAP gene cluster in the human and mouse major histocompatibility complex class II region. These sequences were shown to function as nuclear matrix attachment regions (MARs). Three of the five human MARs and the single mouse MAR recruit heterogeneous nuclear ribonucleoprotein A1 (hnRNP-A1) in vivo during transcriptional up-regulation of the major histocompatibility complex class II genes. The timing of this recruitment correlates with a rise in mature TAP1 mRNA. Two of the human MARs bind hnRNP-A1 in vitro directly within a 35-bp sequence that shows over 90% similarity to certain Alu repeat sequences. This study shows that MARs recruit and bind hnRNP-A1 upon transcriptional up-regulation.

show abstract

Section: Discussionmentioning

confidence: 99%

Recruitment of Heterogeneous Nuclear Ribonucleoprotein A1in Vivo to the LMP/TAP Region of the Major Histocompatibility Complex

Donev

Horton

Beck

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Further understanding of the molecular genetics of the HLA class I region depends on the identification and characterization of many other resident genes, analogous to the progress made in the class II and III regions (4)(5)(6). The susceptibility to a variety of diseases has long been the subject of a plethora of studies on the MHC, primarily a consequence of the immune function of the class I and II loci and their high allelic polymorphism.…”

mentioning

confidence: 99%

The complete genomic sequence of 424,015 bp at the centromeric end of the HLA class I region: Gene content and polymorphism

Guillaudeux

Janer

Wong

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

We report here the genomic sequence of the centromeric portion of HLA class I, extending 424,015 bp from tumor necrosis factor ␣ to a newly identified gene Ϸ20 kb telomeric of Otf-3. As a source of DNA, we used cosmids centromeric of HLA-B that had been mapped previously with conventional restriction digestion and fingerprinting and previously characterized yeast artificial chromosomes subcloned into cosmids and mapped with multiple complete digest methodologies. The data presented provide a description of the gene content of centromeric HLA class I including new data on intron, promoter and f lanking sequences of previously described genes, and a description of putative new genes that remain to be characterized beyond the structural information uncovered. A complete accounting of the repeat structure including abundant di-, tri-, and tetranucleotide microsatellite loci yielded access to precisely localized mapping tools for the major histocompatibility complex. Comparative analysis of a highly polymorphic region between HLA-B and -C was carried out by sequencing over 40 kb of overlapping sequence from two haplotypes. The levels of variation observed were much higher than those seen in other regions of the genome and indeed were higher than those observed between allelic HLA class I loci.

show abstract

“…However, of the 22 class II loci, three were described previously (M2_2_36 by Reiss et al: Immunogenetics; 32: 110 ± 116; M2_2_23 in 12 and M2_4_25 in 4 ). The M2_2_48 STR corresponds to the 13_36829 locus in this work.…”

Section: Note Added In Proofmentioning

confidence: 96%

Short tandem repeat (STR) haplotypes in HLA: an integrated 50-kb STR/linkage disequilibrium/gene map between the RING3 and HLA-B genes and identification of STR haplotype diversification in the class III region

et al. 2001

View full text Add to dashboard Cite

We present a dense STR/linkage disequilibrium(LD)/gene map between the RING3 and HLA-B loci, reference allelic sizes on the most prevalent HLA haplotypes and their allelic frequencies in pedigree founders. This resource will facilitate LD, evolution and gene mapping studies, including comparisons of HLA and STR haplotypes and identification of HLA recombinants. The map was constructed by testing novel and previously reported STRs using a panel of 885 individuals in 211 families and 60 DNA samples from cell lines and bone marrow donors homozygous in the HLA-A, -B and -DR loci selected from over 15 000 entries into the registry of Swedish bone marrow donors. We have also analysed the variability of STR alleles/haplotypes on the most prevalent HLA haplotypes to identify STRs useful for fine mapping of disease genes in the region previously implicated in susceptibility to many disorders. The analysis of 40 HLA-A*01, B*0801, DRB1*03011, DQB1*0201 haplotypes in homozygous donors showed a surprising stability in 23 STRs between the class II recombination hot spot and HLA-B, with the average of 1.9% (16/838) variant alleles. However, 40% variant alleles were found at the D6S2670 locus in intron 19 of the tenascin-X gene both in the families and homozygous donors. The nucleotide sequence analysis of this STR showed a complex polymorphism consisting of tetra-(CTTT) 8 ± 18 and penta-nucleotide (CTTTT) 1 ± 2 repeats, separated by an intervening non-polymorphic sequence of 42 bp. The HLA-A1, B*0801, DRB1*03011, DQB1*0201 haplotypes had five (CTTT) 14 ± 18 /(CTTTT) 2 variants with a predominant (CTTT) 16 allele, implicating the tetranucleotide component as the source of this ancestral haplotype diversification, which may be due to the location of D6S2670 in the region of the highest GC content in the human MHC.

show abstract

Evolutionary Dynamics of Non-coding Sequences Within the Class II Region of the Human MHC

Cited by 77 publications

References 0 publications

Recruitment of Heterogeneous Nuclear Ribonucleoprotein A1in Vivo to the LMP/TAP Region of the Major Histocompatibility Complex

Recruitment of Heterogeneous Nuclear Ribonucleoprotein A1in Vivo to the LMP/TAP Region of the Major Histocompatibility Complex

The complete genomic sequence of 424,015 bp at the centromeric end of the HLA class I region: Gene content and polymorphism

Short tandem repeat (STR) haplotypes in HLA: an integrated 50-kb STR/linkage disequilibrium/gene map between the RING3 and HLA-B genes and identification of STR haplotype diversification in the class III region

Contact Info

Product

Resources

About