An approach to mapping haplotype-specific recombination sites in human MHC class III

Levo, Antti; Westman, Pia; Partanen, Jukka

doi:10.1007/bf00176674

Cited by 8 publications

(3 citation statements)

References 18 publications

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“…96 This particular hotspot is not present in the corresponding region in humans, but there is evidence from a detailed analysis of an MHC haplotype for a recombinational hotspot around the TNF locus (i.e., telomeric to the HSPA1A/B-HLA-DRB fragment). 97 As expected, complotypes show stronger LD with HLA-DRB1 98 and our results suggested that the HSPA1B locus would be in stronger LD with HLA-DRB1. Thus, the HSPA1A/B polymorphisms may be considered as MHC class III lineage markers as they show correlations with evolutionarily ancient HLA class II lineages.…”

Section: Discussionsupporting

confidence: 80%

Conserved extended haplotypes of the major histocompatibility complex: further characterization

et al. 2006

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Since the complete sequencing of a human major histocompatibility complex (MHC) haplotype, interest in non-human leucocyte antigen (HLA) genes encoded in the MHC has been growing. Non-HLA genes, which outnumber the HLA genes, may contribute to or account for HLA and disease associations. Most information on non-HLA genes has been obtained in separate studies of individual loci. To comprehensively address polymorphisms of relevant non-HLA genes in 'conserved extended haplotypes' (CEH), we investigated 101 International Histocompatibility Workshop reference cell lines and nine additional anonymous samples representing all 37 unambiguously characterized CEHs at MICA, NFKBIL1, LTA, NCR3, AIF1, HSPA1A, HSPA1B, BF, NOTCH4 and a single nucleotide polymorphism (SNP) at HLA-DQA1 as well as MICA, NOTCH4, HSPA1B and all five tumour necrosis factor short tandem repeat (STR) polymorphisms. This work (1) provides an extensive catalogue of MHC polymorphisms in all CEHs, (2) unravels interrelationships between HLA and non-HLA haplotypical lineages, (3) resolves reported typing ambiguities and (4) describes haplospecific markers for a number of CEHs. Analysis also identified a DQA1 SNP and segments containing MHC class III polymorphisms that corresponded with class II (DRB3 and DRB4) lineages. These results portray the MHC where lineages containing non-HLA and HLA variants in linkage disequilibrium may operate in concert and can guide more thorough design and interpretation of HLA-disease relationships.

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Section: Discussionsupporting

confidence: 80%

Conserved extended haplotypes of the major histocompatibility complex: further characterization

et al. 2006

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“…The birthplaces in Figure 2C are more scattered, but it should be noted that they actually represent four distinct recombinant haplotypes, all demonstrated to have originated from the A3 Cw6 B47 F10 DR7 haplotype. 19 By studying each recombinant separately, clear clustering can be observed. For example, those with B18 follow the route of the Lestijoki river ( Figure 2C).…”

Section: Geographic Origin Of Haplotypesmentioning

confidence: 99%

Tracing past population migrations: genealogy of steroid 21-hydroxylase (CYP21) gene mutations in Finland

et al. 1999

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The genealogic origin of steroid 21-hydroxylase gene (CYP21) mutations and associated haplotypes was determined in 74 unrelated Finnish families with CYP21 deficiency (congenital adrenal hyperplasia, CAH). These families account for two thirds (85/119) of all diagnosed patients of Finnish descent found in this country. We recently demonstrated that multiple founder mutations each associated with a particular haplotype can be found in Finland. Interestingly, some of the haplotypes were identical to those observed in various European populations, whereas others have not been described elsewhere, indicating a local and perhaps a more recent origin. In the present report we show that each of the major founder haplotypes originates from a particular geographic region of Finland. Thus many local genetic isolates are to be expected in Finland. Our finding is in a clear contrast to the genetic diseases known as the 'Finnish disease heritage', in which only one mutation usually predominates. Some of the CYP21 haplotypes proved very informative for analysis of the history of the Finnish population. For example, the origin of one frequent haplotype was shown to cluster in a region assumed by archaeological data to be a major site of immigration by settlers of either Scandinavian or Baltic origin during the first centuries AD. As this haplotype is frequent in many European patient populations, we provide independent genetic evidence of this Iron Age immigration. On the other hand, another frequent haplotype found solely in Finland reflects a more recent (post 15th century) settlement expansion. Consequently, well characterised and sufficiently frequent autosomal gene markers can provide useful information on migrations both between and within populations.

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“…Studies in mice suggest that MHC recombination preferentially occurs in certain regions (hot spots) (10, 11). Recombination frequencies do vary in a haplotype‐dependent manner in the mouse MHC (12), but despite suggestions of a similar situation in humans (13, 14), the large number of haplotypes and uncontrollable mating patterns preclude the ability to draw similar conclusions. In this sense, it has been tested in the 12th International Histocompatibility Workshop whether certain alleles from HLA‐B locus were more commonly involved than others in recombinations (11).…”

Section: Resultsmentioning

confidence: 99%

Report of recombinations between HLA loci within two families: utility of high resolution typing

Muro

Moya-Quiles

Marı́n

et al. 2002

Clinical Transplantation

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We have analysed two Caucasian families in which recombinant individuals have been identified. In both families, initial low resolution typing of class I and II antigens of possible patients referred for bone marrow transplantation and their respective potential donors (based on inherited haplotypes analysis) revealed them to be HLA identical and supposedly inheriting-non-recombinant haplotypes. The mothers were found to be DRB1*04 generic allele homozygous, but possessing two DRB1*04 specific alleles, DRB1*0403 and DRB1*0404 (family A) and DRB1*0401 and DRB1*0402 (family B). In both cases the patients inherited a maternal haplotype that is the result of a recombination event between the mother's HLA-DRB1 and -B genes on their chromosomes. Based on linkage disequilibrium it is likely that the recombinant haplotypes are present in the patients rather than their brothers. In both families, the results of the MLC in terms of relative response was positive. Thus, these cases illustrate the importance of high resolution DNA class II typing when assignment of MHC antigens is of extreme importance (i.e. bone marrow transplantation).

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An approach to mapping haplotype-specific recombination sites in human MHC class III

Cited by 8 publications

References 18 publications

Conserved extended haplotypes of the major histocompatibility complex: further characterization

Conserved extended haplotypes of the major histocompatibility complex: further characterization

Tracing past population migrations: genealogy of steroid 21-hydroxylase (CYP21) gene mutations in Finland

Report of recombinations between HLA loci within two families: utility of high resolution typing

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