HLA B7-DR15-DQ6
Encyclopedia
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 (share a recent common ancestor for that segment of the chromosome). Chromosomal recombination
fragments multigene haplotypes as the distance to that ancestor increases in number of generations.
HLA B7-DR15-DQ6 is a representation(by serotype
) of a common HLA haplotype
found in Western Eurasia. The haplotype can be written in an extended form covering the major histocompatibility loci as follows:
The older literature may describe this haplotype in two different ways. One B7-DR2-DQ6 derives from the fact that DR15 is a split antigen of the DR2 broad antigen serotype. The other B7-DR2-DQ1 stems from the fact that DQ1 is an alpha chain serotype that is now covered by the beta chain type DQ5 and DQ6 (DQ1 pairs with DQ5 and DQ6 by cis-haplotype pairing).
There are two major subhaplotypes one that is preceded on its telomer
ic side by HLA A*0301 and the other by HLA A*0201. The A*0301 bearing haplotype (HLA A3-B7-DR15-DQ6) is described as the longest known multgene haplotype in humans.
The gene-allele representation of the haplotype is:
This is considered now the longest of the widely distributed ancestral haplotypes, its length is 4.8 million nucleotides and extends from TRIM27 gene . . . .The haplotype is nodal in Ireland but is also at high frequency in Switzerland, it has a subnode in the Pasiegos of northern Spain. There is some variance in the distribution of A3::DQ6 relative to A1::DQ2 in that there is more of a bias toward central and eastern Europe. Parts of the haplotype are spread into East Asia and even appear within the New world's indigeonous populations. DR15:DQ6 frequencies peak in central Asia, and it is suspect that this may be a point of Eurasian spread westward into Europe.
While there are some diseases associated with the haplotype, the frequency of association is less compared to A1::B8.
in a Greek
population.
DR2 (15 or 16) -DQ6.2 has been found to associate with (idiopathic) narcolepsy
-cataplexy
Hypocretin ligand deficiency in the brain and cerebrospinal fluid
is also link to narcolepsy-cataplexy. DR15-DQ6 also shows an association with factors (including a genetic factor on chromosome 12p12) involved in familial multiple sclerosis
DR15-DQ6 is strongly associated with the development of choroidal neovascular lesions in presumed ocular histoplasmosis
syndrome.
The DR15-DQ6 haplotype may afford some greater protection against the progression of HIV
. However, the haplotype is a risk factor in cervical cancer
.
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
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 (share a recent common ancestor for that segment of the chromosome). Chromosomal recombination
Genetic recombination
Genetic recombination is a process by which a molecule of nucleic acid is broken and then joined to a different one. Recombination can occur between similar molecules of DNA, as in homologous recombination, or dissimilar molecules, as in non-homologous end joining. Recombination is a common method...
fragments multigene haplotypes as the distance to that ancestor increases in number of generations.
HLA B7-DR15-DQ6 is a representation(by serotype
Serotype
Serotype or serovar refers to distinct variations within a subspecies of bacteria or viruses. These microorganisms, viruses, or cells are classified together based on their cell surface antigens...
) of a common HLA haplotype
Haplotype
A haplotype in genetics is a combination of alleles at adjacent locations on the chromosome that are transmitted together...
found in Western Eurasia. The haplotype can be written in an extended form covering the major histocompatibility loci as follows:
HLA Cw*0702 : B*0702 : DRB1*1501 : DQA1*0102 : DQB1*0602
The older literature may describe this haplotype in two different ways. One B7-DR2-DQ6 derives from the fact that DR15 is a split antigen of the DR2 broad antigen serotype. The other B7-DR2-DQ1 stems from the fact that DQ1 is an alpha chain serotype that is now covered by the beta chain type DQ5 and DQ6 (DQ1 pairs with DQ5 and DQ6 by cis-haplotype pairing).
There are two major subhaplotypes one that is preceded on its telomer
Telomer
The word telomer has two distinct, yet related meanings.*Its original meaning is in polymer science, when telomerization results in an extremely small polymer—one whose degree of polymerization is generally between 2 and 5....
ic side by HLA A*0301 and the other by HLA A*0201. The A*0301 bearing haplotype (HLA A3-B7-DR15-DQ6) is described as the longest known multgene haplotype in humans.
HLA A2-B7-DR15-DQ6
The appendation of the B7::DQ6 haplotype creates the A2-B7::DQ6 haplotype. This haplotype if found often in Northern Spain, Switzerland, Netherlands.HLA A*0201Cw*0702 : B*0702 : DRB1*1501 : DQA1*0102 : DQB1*0602
HLA A3-B7-DR15-DQ6
| freq | Rank in | |||
| ref. | Population | (%) | Pop. | |
| Swiss | 9.1 | 1 | ||
| Ireland | 8.6 | |||
| Austria | 7.4 | 1 | ||
| Northern Ireland | 6.5 | 1 | ||
| Netherlands | 6.6 | |||
| Belgium | 6.0 | 1 | ||
| Swedish | 5.7 | 3 | ||
| German | 5.7 | |||
| Polish | 4.9 | |||
| Romanian | 3.8 | |||
| Armenia | 3.7 | |||
| Portuguese | 3.4 | |||
| British | 3.4 | |||
| Czech | 3.1 | |||
| Svans | 2.7 | |||
| Albania | 2.7 | |||
| Tuscan Italy | 2.7 | |||
| Spanish | 2.6 | |||
| Basque | 2.5 | |||
| Italy | 1.6 | |||
| Greek | 1.3 | |||
| Bulgaria | 1.1 | |||
| 1 Cw*0702 (Europe) | ||||
The gene-allele representation of the haplotype is:
HLA A*0301Cw*0702 : B*0702 : DRB1*1501 : DQA1*0102 : DQB1*0602
This is considered now the longest of the widely distributed ancestral haplotypes, its length is 4.8 million nucleotides and extends from TRIM27 gene . . . .The haplotype is nodal in Ireland but is also at high frequency in Switzerland, it has a subnode in the Pasiegos of northern Spain. There is some variance in the distribution of A3::DQ6 relative to A1::DQ2 in that there is more of a bias toward central and eastern Europe. Parts of the haplotype are spread into East Asia and even appear within the New world's indigeonous populations. DR15:DQ6 frequencies peak in central Asia, and it is suspect that this may be a point of Eurasian spread westward into Europe.
While there are some diseases associated with the haplotype, the frequency of association is less compared to A1::B8.
Disease Associations
HLA B7-DR15-DQ6 was found to have an association with postmenopausal osteoporosisOsteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
in a Greek
Greeks
The Greeks, also known as the Hellenes , are a nation and ethnic group native to Greece, Cyprus and neighboring regions. They also form a significant diaspora, with Greek communities established around the world....
population.
DR2 (15 or 16) -DQ6.2 has been found to associate with (idiopathic) narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
-cataplexy
Cataplexy
Cataplexy is a sudden and transient episode of loss of muscle tone, often triggered by emotions. It is a rare disease , but affects roughly 70% of people who have narcolepsy...
Hypocretin ligand deficiency in the brain and cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
is also link to narcolepsy-cataplexy. DR15-DQ6 also shows an association with factors (including a genetic factor on chromosome 12p12) involved in familial multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
DR15-DQ6 is strongly associated with the development of choroidal neovascular lesions in presumed ocular histoplasmosis
Histoplasmosis
Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum. Symptoms of this infection vary greatly, but the disease primarily affects the lungs...
syndrome.
The DR15-DQ6 haplotype may afford some greater protection against the progression of HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
. However, the haplotype is a risk factor in cervical cancer
Cervical cancer
Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
.