HLA-DQ7

Last updated
DQ Illustration.PNG
major histocompatibility complex, class II, DQ7
HaplotypesDQA1*03:02:DQB1*03:01 DQA1*03:03:DQB1*03:01 DQA1*04:01:DQB1*03:01 DQA1*05:05:DQB1*03:01 DQA1*06:01:DQB1*03:01
Structure (See HLA-DQ)
Identifiers
alpha 1 *0302*0303*0401*0505*0601
Symbol(s) HLA-DQA1 [ permanent dead link ]
EBI-HLA DQA1*0302
EBI-HLA DQA1*0303
EBI-HLA DQA1*0401
EBI-HLA DQA1*0505
EBI-HLA DQA1*0601
Identifiers
beta 1 *0301*0304
Symbol(s) HLA-DQB1
EBI-HLA DQB1*0301
EBI-HLA DQB1*0304
Shared data
Locus chr.6 6p21.31

HLA-DQ7 (DQ7) is an HLA-DQ serotype that recognizes the common HLA DQB1*0301 [1] and the less common HLA DQB1*0304 gene products. DQ7 is a form of 'split antigen' of the broad antigen group DQ3 which also contains DQ8 and DQ9.

Contents

DQ7 is linked by haplotype to a number of DQA1 (DQ alpha chain) genes, producing in cis-haplotype form, a large number of DQ αβ isoforms. These DQ alpha chains are also known to form transhaplotype isomers with other HLA-DQ.

DQ7 is linked to the following alpha chains genes (DQA1*)

Serology

DQ3, DQ7, DQ8, and DQ9 recognition of Some DRB1*and [2]
DQB1*DQ7DQ3DQ8Sample
allele % % %size (N)
03018540112220
030440358111

Serotyping efficiency. The serotyping efficiency of DQ7 toward DQB1*0301 is reasonably good, but still results in some false negatives, for *0304 the typing efficiency is poor and cross-reaction with DQ8 is relatively high.

Alleles

DQB1*0301

DQB1*0301 is the major DQ7 allele DQB1*0301 appears to be associated with lupus anticoagulant. [3]

DQB1*0304

DQB1*0304 is the minor DQ7 allele

Haplotypes

HLA DQA1*03:DQB1*0301 frequencies
freq
ref.Population(%)
[4] Chukotka Chukchi (Siberia)26.7
[4] Chukotka Eskimos (Siberia)25.0
[4] Koryaks (NE Kamchatka, Siberia)19.1
[4] Polygus Evenks (Siberia)11.4
[4] Khalkh (Ulaanbaatar, Mongolia)11.0
[4] Negidal (Siberia)9.6
[4] Kushun Buryat (Siberia)8.0
[4] Tarialan Khoton (Mongolia)7.8
[4] France Ceph6.0
[4] Russia Tuva (2)6.0
[4] Udegeys Gvaysugi (Siberia)4.8
[4] Irkutsk Tofalar (Siberia )4.7
[4] Ulchi (Siberia)4.1
[4] Belgian pop24.1
[4] England Caucasoid4.0
[4] Italy pop 22.8
[4] Russia Tuva Todja2.3
[4] China Ürümqi Kazak2.4
[4] Sulamai Kets (Siberia)2.3
[4] Russia Siberia Nganasan Dudinka2.1
[4] NW Slavic Russia2.0
[4] Japan Fukuoka1.2
[4] Japan (2)1.1

DQ haplotypes of this serotype are formed between the cis-chromosomal genes of the DQA1 locus. This includes DQA1*0301, *0302, *0303, *0401, *0505, *0601.

There is a rather large degree of disequilibration about DQA1*0301 suggesting that this is one of the older and more established HLA DQB1* alleles in Eurasia. The intron structure of DQB1 suggest that DQB1*0301 DQB1*0302/*0303 split occurred before DQB1*0302/*0303, the distribution of *03 in Africa suggest that recombination DQA1*03:DQB1*0301 are primarily the result of recombination events that have occurred in Africa. A recent study of myasthenia gravis in Houston confirms the presence of A*0505:B*0301 in Nigeria. B1*0301 and A1*03 haplotypes are found at relatively high frequencies in SE Asia and Austronesia, also indicating that it is well established in the exo-African population.

DQ7.3

The DQ7.3 haplotype can be formed by DQA1*0301:DQB1*0301, DQA1*0302:DQB1*0301, DQA1*0303:DQB1*0301. In the west, the DQA1*0303:DQB1*0301 haplotype appears to be more common. The gene products of all 3 function similarly and subunits are interchangeable. In the literature, older DNA tests recognize DQA1*0303 as DQA1*0302, and still oldest DNA tests recognize all three as DQA1*03 or DQA1*0301.

DQA1*0303:DQB1*0301 may be involved in narcolepsy. [5] DQ7.3 appears to be associated with oral ulcerations and gingival disease [6]

DQ7.4

HLA DQA1*0401:DQB1*0301
freq
ref.Population(%)
[4] Chukotka Chukchi (Siberia)9.5
[4] Gvaysugi Udegeys (Siberia)9.5
[4] Chukotka Eskimos (Siberia)8.7
[4] Polygus Evenks (Siberia)7.2
[4] NE Koryaks (Kamchatka)6.5
[4] Cameroon Saa4.4
[4] Sulamai Kets (Siberia)2.3
[4] Gambia1.4
[4] Fukuoka Japan1.2
[7] Caucasian Americans0.3

DQA1*0401:DQB1*0301 (DQ7.4) This haplotype is found in Siberia, Africa but also at low levels in Western Europe.

DQ7.5

HLA DQA1*0505 frequencies
freq
ref.Population(%)
[4] Lebanon (estimated)40.0
[4] Italy Rome29.6
[4] Netherlands (2)15.5
[4] Tunisia14.6
[4] England (2)10.1
[4] South Korea6.8
[4] Congo Kinshasa Bantu4.4

DQA1*0505:DQB1*0301 (DQ7.5) was gene-typed as DQA1*0501:DQB1*0301 until it was recognized that there was amino acid sequence variant in the preprocessed DQA1* gene product (proto-α-chain polypeptide encoded DQA1*0505). This proto-alpha, once processed, is identical to the DQA1*0501 encoded α-chain once it is processed. Almost 100% of DQ7.5 haplotypes carry the DQA1*0505 allele. [8] The DR5-DQ7.5 is common in the Southeastern Europe and the Levant, with DQ7.5 reaching a haplotype frequency of 40% in Lebanon. Its high level is probably not by chance, the haplotype appears to protect against juvenile diabetes, which appears to be more common among cereal eating peoples. [9] Cereals were first domesticated in the Near and Middle East more than 10,000 years ago and selection may explain DQ7.5's higher frequencies. (See: Triticeae)

The processed alpha subunit of DQA1*0505 is identical to that of DQA1*0501, but some slight differences in the association with autoimmune disease are observed, possibly as a result of linked DR and DQB1 genes. DQA1*0505 can play into celiac disease under two circumstances. First it can increase risk when DQ2.5 is present, although current studies indicate that it marginally increases risk relative to DQB1*0202 in DQ2.5 cis haplotype. DQA1*0505, without DQ2, is found in a small percentage of coeliac disease (without DQ2 or DQ8). [10]

DQ7.5 is found also high in frequency in the new world, but with DR types less commonly encountered in the old world. DQA1*05 allele is not clear in the new world. DQB1*0301 may be under current positive selection in the human population, at least in areas where DQ2.5 and DQ8 are high, as it confers resistance to type 1 diabetes. For hepatitis type B, DQ7 is associated with persistence but for C, DQ7 is associated with clearance. [11] DQA1*0505, DQB1*0301 appear to increase the risk for melanoma in the Spanish population however this may have a linkage to more recent fair skinned migrants. DQB1*0301 is also associated with allergic fungal sinusitis, human papillomavirus (HPV) induced warts, limited cutaneous systemic sclerosis in Africans, and primary sclerosing cholangitis in Southern Europeans. DQB1*0301 is also predisposing in narcolepsy. [5] DQB1*0301 does not to play a role in any frequently occurring autoimmune disease and its presence in the near east and suppressed frequencies of coeliac disease and Type 1 diabetes in these regions is suggestive that it has a positive selection in Post-Mesolithic cereal based societies in the Western Eurasia.

DQB1*0301 appears to be more associated with early onset myasthenia gravis in Japanese than DQ8, and was also found along with DQB1*0304 to be associated with Chinese MG. DQ7 or associated DR types may play a role in rheumatoid arthritis. In celiac disease the DQ7 (A*0505/1) can mediate celiac disease when HLA DQ2.2 is also present. HLA DQB1*0301 in Turks is associated with Thymoma but the risk may be associated with HLA class I loci.

DQ7.6

HLA DQA1*0601 frequencies
freq
ref.Population(%)
[4] Java Yogyakarta48.1
[4] Kiribati37.9
[4] Nauru28.4
[4] Harbin City (Manchuria, China)12.8
[4] Thailand12.7
[4] South Korean (5)4.4
[4] China Beijing and Xian3.5
[4] Japan3.0
[4] India Bombay1.7
[4] England Caucasoid0.6
[4] Italy Central0.6
[4] Algeria10.5
[4] Cameroon0.4

DQA1*0601:DQB1*0301 (DQ7.6) is a globally rare haplotype, however it is found at high frequencies in the South Pacific and along the West Pacific rim. DQB1*0301 appears to be uniquely linked to DQA1*0601. DQ7.6 is positively associated with asthma, [12] pauciarticular juvenile arthritis without anti-nuclear antibodies, [13] DQ7.6 is negatively associated (Protective against) juvenile diabetes, [14] liver and spleen disease in Schistosoma japonicum infection, [15] pulmonary tuberculosis. [16]

Related Research Articles

<span class="mw-page-title-main">Human leukocyte antigen</span> Genes on human chromosome 6

The human leukocyte antigen (HLA) system or complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals.

<span class="mw-page-title-main">HLA-DQ</span> Cell surface receptor protein found on antigen-presenting cells.

HLA-DQ (DQ) is a cell surface receptor protein found on antigen-presenting cells. It is an αβ heterodimer of type MHC class II. The α and β chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromosome band 6p21.3. Both α-chain and β-chain vary greatly. A person often produces two α-chain and two β-chain variants and thus 4 isoforms of DQ. The DQ loci are in close genetic linkage to HLA-DR, and less closely linked to HLA-DP, HLA-A, HLA-B and HLA-C.

HLA DR3-DQ2 is double serotype that specifically recognizes cells from individuals who carry a multigene HLA DR, DQ haplotype. Certain HLA DR and DQ genes have known involvement in autoimmune diseases. DR3-DQ2, a multigene haplotype, stands out in prominence because it is a factor in several prominent diseases, namely coeliac disease and juvenile diabetes. In coeliac disease, the DR3-DQ2 haplotype is associated with highest risk for disease in first degree relatives, highest risk is conferred by DQA1*0501:DQB1*0201 homozygotes and semihomozygotes of DQ2, and represents the overwhelming majority of risk. HLA DR3-DQ2 encodes DQ2.5cis isoform of HLA-DQ, this isoform is described frequently as 'the DQ2 isoform', but in actuality there are two major DQ2 isoform. The DQ2.5 isoform, however, is many times more frequently associated with autoimmune disease, and as a result to contribution of DQ2.2 is often ignored.

<span class="mw-page-title-main">HLA-DQ8</span>

HLA-DQ8 (DQ8) is a human leukocyte antigen serotype within the HLA-DQ (DQ) serotype group. DQ8 is a split antigen of the DQ3 broad antigen. DQ8 is determined by the antibody recognition of β8 and this generally detects the gene product of DQB1*0302.

<span class="mw-page-title-main">HLA-DQ2</span>

HLA-DQ2 (DQ2) is a serotype group within HLA-DQ (DQ) serotyping system. The serotype is determined by the antibody recognition of β2 subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ2 are encoded by the HLA-DQB1*02 allele group. This group currently contains two common alleles, DQB1*0201 and DQB1*0202. HLA-DQ2 and HLA-DQB1*02 are almost synonymous in meaning. DQ2 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively.

<span class="mw-page-title-main">HLA-DQ4</span>

HLA-DQ4 (DQ4) is a serotype subgroup within HLA-DQ(DQ) serotypes. The serotype is determined by the antibody recognition of β4 subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ4 are encoded by the HLA-DQB1*04 allele group. This group currently contains 2 common alleles, DQB1*0401 and DQB1*0402. HLA-DQ4 and HLA-DQB1*04 are almost synonymous in meaning. DQ4 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ4.3 and DQ4.4, are also encoded by the DQA1*0303 and DQA1*0401 genes, respectively.

<span class="mw-page-title-main">HLA-DQ5</span>

HLA-DQ5 (DQ5) is a human leukocyte antigen serotype subgroup within HLA-DQ(DQ) serotypes. The serotype is determined by the antibody recognition of β5.x subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ5 are encoded by the HLA-DQB1*05 allele group. This group currently contains 4 common alleles, DQB1*0501, *0502, *0503, and *0504. HLA-DQ5 and HLA-DQB1*05 are almost synonymous in meaning. DQ5 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, are all HLA-DQ1 encoded by the DQA1*01 allele group.

<span class="mw-page-title-main">HLA-DQ6</span>

HLA-DQ6 (DQ6) is a human leukocyte antigen serotype within HLA-DQ (DQ) serotype group. The serotype is determined by the antibody recognition of β6 subset of DQ β-chains. The β-chain of DQ isoforms are encoded by HLA-DQB1 locus and DQ6 are encoded by the HLA-DQB1*06 allele group. This group currently contains many common alleles, DQB1*0602 is the most common. HLA-DQ6 and DQB1*06 are almost synonymous in meaning. DQ6 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. For DQ6, however, cis-isoform pairing only occurs with DQ1 α-chains. There are many haplotypes of DQ6.

<span class="mw-page-title-main">HLA-DQ9</span>

HLA-DQ9 (DQ9) is a human leukocyte antigen serotype within the HLA-DQ (DQ) serotype group. DQ9 is a split antigen of the DQ3 broad antigen. DQ9 is determined by the antibody recognition of β9 and this generally detects the gene product of DQB1*0303.

<span class="mw-page-title-main">HLA-DQ1</span> Serotype that covers a broad range of HLA-DQ haplotypes.

HLA-DQ1 is a serotype that covers a broad range of HLA-DQ haplotypes. Historically it was identified as a DR-like alpha chain called DC1; later, it was among 3 types DQw1, DQw2 and DQw3. Of these three serotyping specificities only DQw1 recognized DQ alpha chain. The serotype is positive in individuals who bear the DQA1*01 alleles. The most frequently found within this group are: DQA1*0101, *0102, *0103, and *0104. In the illustration on the right, DQ1 serotyping antibodies recognizes the DQ α (magenta), where antibodies to DQA1* gene products bind variable regions close to the peptide binding pocket.

<span class="mw-page-title-main">HLA-DQ3</span>

Within molecular and cell biology, HLA-DQ3 (DQ3) is a broad serotype category with split antigens HLA-DQ7, DQ8, and DQ9. Historically, originally recognized as MB3 a DC4 serotype, DQw3 was one of three early determined antigens recognized as HLA-DQ along with HLA-DQ1 and HLA-DQ2. While the DQ3 molecules are structurally similar in beta chain, the DQ molecules differ markedly in function, even when present with the same DQ alpha subunit. For this reason they are best treated independently.

<span class="mw-page-title-main">HLA-DR17</span>

HLA-DR17 (DR17) is an HLA-DR serotype that recognizes the DRB1*0301 and *0304 gene products. DR17 is found at high frequency in Western Europe. DR17 is part of the broader antigen group HLA-DR3 and is very similar to the group HLA-DR18.

<span class="mw-page-title-main">HLA-DR11</span>

HLA-DR11 (DR11) is a HLA-DR serotype that recognizes the DRB1*1101 to *1110. DR11 serotype is a split antigen of the older HLA-DR5 serotype group which also contains the similar HLA-DR12 antigens.

<span class="mw-page-title-main">HLA-DR12</span>

HLA-DR12(DR12) is a HLA-DR serotype that recognizes the DRB1*1201 to *1203, *1206. DR12 serotype is a split antigen of the older HLA-DR5 serotype group which also contains the similar HLA-DR11 antigens.

<span class="mw-page-title-main">HLA-DR7</span>

HLA-DR7 (DR7) is a HLA-DR serotype that recognizes the DRB1*0701 to *0705 gene products.

<span class="mw-page-title-main">HLA-DR3</span>

HLA-DR3 is composed of the HLA-DR17 and HLA-DR18 split 'antigens' serotypes. DR3 is a component gene-allele of the AH8.1 haplotype in Northern and Western Europeans. Genes between B8 and DR3 on this haplotype are frequently associated with autoimmune disease. Type 1 diabetes mellitus is associated with HLA-DR3 or HLA-DR4. Nearly half the US population has either DR3 or DR4, yet only a small percentage of these individuals will develop type 1 diabetes.

In autoimmune disease, anti-apolipoprotein H (AAHA) antibodies, also called anti-β2 glycoprotein I antibodies, comprise a subset of anti-cardiolipin antibodies and lupus anticoagulant. These antibodies are involved in sclerosis and are strongly associated with thrombotic forms of lupus. As a result, AAHA are strongly implicated in autoimmune deep vein thrombosis.

<span class="mw-page-title-main">HLA-A33</span>

HLA-A33 (A33) is a human leukocyte antigen serotype within HLA-A serotype group. The serotype is determined by the antibody recognition of α33 subset of HLA-A α-chains. For A33, the alpha "A" chain are encoded by the HLA-A*33 allele group and the β-chain are encoded by B2M locus. A33 and A*33 are almost synonymous in meaning. A33 is a split antigen of the broad antigen serotype A19. A33 is a sister serotype of A29, A30, A31, A32, and A74.

HLA A1-B8-DR3-DQ2 haplotype is a multigene haplotype that covers a majority of the human major histocompatibility complex on chromosome 6. A multigene haplotype is set of inherited alleles covering several genes, or gene-alleles; common multigene haplotypes are generally the result of descent by common ancestry. Chromosomal recombination fragments multigene haplotypes as the distance to that ancestor increases in number of generations.

HLA B7-DR15-DQ6 is a multigene haplotype that covers a majority of the human major histocompatibility complex on chromosome 6. A multigene haplotype is set of inherited alleles covering several genes, or gene-alleles, common multigene haplotypes are generally the result of descent by common ancestry. Chromosomal recombination fragments multigene haplotypes as the distance to that ancestor increases in number of generations.

References

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  2. derived from IMGT/HLA
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