Mutations and selection in the generation of class II histocompatibility antigen polymorphism.

Gustafsson, Kenth; Wiman, Klas G.; Emmoth, Eva; Larhammar, Dan; Böhme, Jan; Hyldig‐Nielsen, J. J.; Ronne, Hans; Peterson, Per A.; Rask, Lars

doi:10.1002/j.1460-2075.1984.tb02026.x

Cited by 226 publications

(75 citation statements)

References 47 publications

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“…4 and Table 1). Furthermore, as has been observed previously (26), the majority of nucleotide differences outside the first domain are silent, presumably reflecting structural and functional constraints, while the majority of nucleotide differences within the first domain result in amino acid differences. It should also be noted that many of the amino acid differences are clustered within an area (positions 45-56) previously suggested to be "hypervariable" (38).…”

Section: Methodssupporting

confidence: 67%

“…No recombinational event between DQ and DR has yet been confirmed, suggesting a relatively low frequency of recombination. Biochemical studies (2,(12)(13)(14)(15)(16)(17)(18) and analysis of cDNA clones (19)(20)(21)(22)(23)(24)(25)(26) indicate that a majority of the Ia genes are expressed as products. Ia gene products belonging to the same group are highly related (greater than 95% protein homology) while those belonging to different groups are only approximately 60% related.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nucleotide sequence of an HLA-DQ alpha chain derived from a DRw9 cell line: genetic and evolutionary implications.

Moriuchi¹,

Moriuchi²,

Silver³

1985

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

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Three families of human Ia molecules, DP, DQ, and DR, have previously been defined. A cDNA clone, pDSH-9.1, encoding the a chain of a DQ molecule derived from an HLA-DRw9 homozygous cell line has been isolated and sequenced. Comparison of the nucleotide and predicted protein sequence to those of other DQ a subunits reveals that DQ a subunits derived from DR4, -7, and -9 cells are very similar to each other but quite different from a DQ a subunit derived from a DRw6 cell line. These studies suggest that certain Ia haplotypes have a common evolutionary history. Furthermore, in the context of current serologic and biochemical knowledge, they suggest that the gene encoding the DQ a subunit is in strong linkage disequilibrium with the DR locus.The Ia region of the major histocompatibility complex (MHC) consists of a series of closely linked loci encoding cell surface molecules that regulate the immune response. These Ia molecules may be divided into three groups, DP (formerly known as SB) (1), DQ (formerly known as DS) (2), and DR (3), that are structurally distinct. Ia molecules consist of two subunits, a and ,3, with molecular weights of approximately 28,000 and 33,000. Within each group, DP, DQ, and DR, multiple a-and /8-chain gene loci have been described; at present seven P3 chain (two DP, two DQ, and three DR) and five a chain (two DP, two DQ, and one DR) gene loci have been identified (4-9). Although their precise genetic order is not yet known, the DP locus is known to be centromeric to both DQ and DR, which in turn are centromeric to the class I loci, HLA-A, -B, and -C (10). Recombinational analysis indicates that both DP and the class I loci are approximately 1 centimorgan from the DQ and DR loci (10,11). No recombinational event between DQ and DR has yet been confirmed, suggesting a relatively low frequency of recombination. Biochemical studies (2,(12)(13)(14)(15)(16)(17)(18) and analysis of cDNA clones (19)(20)(21)(22)(23)(24)(25)(26) indicate that a majority of the Ia genes are expressed as products. Ia gene products belonging to the same group are highly related (greater than 95% protein homology) while those belonging to different groups are only approximately 60% related.The Ia system is highly polymorphic. At least 11 alleles at the DR locus (designated numerically-i.e., DR1-DR11) have been defined serologically (27). Similarly, at least 6 alleles at the DQ locus and 6 at the DP locus have been defined biochemically and by cellular assays, respectively (27,28 (29). Similarly, cells typing as DR1, -2, and -6 frequently display the MB1 antigenic determinant (30).Although the molecular basis for these antigenic determinants is not known, in some instances, the gene products expressing them have been identified. Thus, MB1, which is expressed on Drl, -2, and -6 cells, and MB3, which is expressed on DR4 and DR5 cells, are both present on different allelic forms of DQ molecules (28,31,32). In other instances, the molecular assignment has been more controversial; MT3 has been localized to DR-like mol...

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Section: Methodssupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Nucleotide sequence of an HLA-DQ alpha chain derived from a DRw9 cell line: genetic and evolutionary implications.

Moriuchi¹,

Moriuchi²,

Silver³

1985

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

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“…It has been speculated that this degree of diversity is a correlate of the biological functions of the molecules encoded in the MHC region. The extensive population polymorphism of the MHC genes may have resulted from selective pressures and functional adaptations [8][9][10]. It has been shown that the highest degree of variability of MHC proteins is found in residues pointing toward the peptide-binding region [11,12].…”

Section: Genetic and Functional Variation Of Major Histocompatibilitymentioning

confidence: 99%

Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations

Viña

Hollenbach²,

Lyke

et al. 2012

Phil. Trans. R. Soc. B

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The human leucocyte antigen (HLA) system shows extensive variation in the number and function of loci and the number of alleles present at any one locus. Allele distribution has been analysed in many populations through the course of several decades, and the implementation of molecular typing has significantly increased the level of diversity revealing that many serotypes have multiple functional variants. While the degree of diversity in many populations is equivalent and may result from functional polymorphism(s) in peptide presentation, homogeneous and heterogeneous populations present contrasting numbers of alleles and lineages at the loci with high-density expression products. In spite of these differences, the homozygosity levels are comparable in almost all of them. The balanced distribution of HLA alleles is consistent with overdominant selection. The genetic distances between outbred populations correlate with their geographical locations; the formal genetic distance measurements are larger than expected between inbred populations in the same region. The latter present many unique alleles grouped in a few lineages consistent with limited founder polymorphism in which any novel allele may have been positively selected to enlarge the communal peptide-binding repertoire of a given population. On the other hand, it has been observed that some alleles are found in multiple populations with distinctive haplotypic associations suggesting that convergent evolution events may have taken place as well. It appears that the HLA system has been under strong selection, probably owing to its fundamental role in varying immune responses.

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“…Recombinant plasmid DNA was isolated from seven clones and sequenced by the dideoxy chain termination method in both directions. To ensure specific amplification of platelet's RNA, RT-PCR reactions were performed using a set of oligonucleotide primers for the non-polymorphic domain of the beta chain gene of class II HLA-DR molecule (which is found predominantly on the surface of activated T-cells, B-cells, and antigen-presenting cells) [19] and in a different reaction, the same platelet's RNA was used in RT-PCR with synthetic oligonucleotides based on the sequence of the platelet membrane glycoprotein lib (GPIIb) [20] as described by Gardella et al [21]. PCR amplification using oligonucleotides 03F and 03R, was performed for 25 cycles of 30 s at 94°C, 30 s at 52°C, and 40 s at 72°C.…”

Section: Pcr Amplification and Dna Sequencingmentioning

confidence: 99%

Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes

Vidal¹,

Ghiso²,

Wısnıewskı³

et al. 1996

FEBS Letters

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The presenilin 1 (PSI) gene located on chromosome 14 has been linked with the majority of early-onset FAD. The normal biological role of PS1 as well as the mechanism by which mutations in PSI cause FAD remains unknown. PSI expression in platelets and the Dami megakaryocytic cell line was examined by Western blot analysis and RT-PCR. Using an anti-Nterminus PS1 antibody we detected PSI immunoreactive bands of 44, 32 and 27 kDa in both cell types. After RT-PCR we observed that platelets and megakaryocytes carry at least four different PSI transcripts. One of them is a novel PSI splice variant that lacks the coding sequence for exon 10 resulting in a shorter 409 amino acid protein.

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Mutations and selection in the generation of class II histocompatibility antigen polymorphism.

Cited by 226 publications

References 47 publications

Nucleotide sequence of an HLA-DQ alpha chain derived from a DRw9 cell line: genetic and evolutionary implications.

Nucleotide sequence of an HLA-DQ alpha chain derived from a DRw9 cell line: genetic and evolutionary implications.

Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations

Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes

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