PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Haplotype”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1992

Haplotypes in SS patients from Nigeria; characterization of one atypical beta S haplotype no. 19 (Benin) associated with elevated HB F and high G gamma levels.

We have determined the haplotypes of 669 beta S and 109 beta A chromosomes from numerous members of 297 Nigerian families of various ethnic backgrounds. Among the beta S chromosomes, haplotype 19 was detected in 93.2%, haplotype 17 in 3.4%, and haplotype 20 in 0.1%, while 2.4% represented atypical haplotypes. As many as 60.6% of the beta A chromosomes exhibited haplotype 19 mutations, 8.2% had haplotype 3, and 1.8% had haplotype 20. Two siblings with elevated Hb F and G gamma levels were heterozygous for a beta S chromosome with haplotype 19 and a second chromosome with a hybrid haplotype (termed 19 B). In this hybrid chromosome, haplotype 3-like locus control region (LCR) [hypersensitive site-2 (HS-2)] sequences are in juxtaposition to those of the 5' flanking region of the G gamma promoter of a beta S chromosome with haplotype 19. The presence of this hybrid chromosome is associated with high G gamma values in individuals with both sickle cell anemia (SS) and sickle cell trait (AS); it closely resembles another hybrid beta S chromosome, termed 19 A, observed in a previously reported Turkish SS patient who was homozygous for this chromosome and had high Hb F and high G gamma values. In both instances, it is hypothesized that the haplotype 3-like sequences of the LCR HS-2 contain genetic determinants that can combine with factors produced during hematopoietic stress, resulting in increased gamma-globin gene expression.

Adolescent↗
PubMed1992

Ancestral haplotypes: conserved population MHC haplotypes.

We describe here a number of Caucasoid MHC haplotypes that extend from HLA-B to DR and that have been conserved en bloc. These haplotypes and recombinants between any two of them account for 73% of unselected haplotypes in our Caucasoid population. The existence of ancestral haplotypes implies conservation of large chromosomal segments. Irrespective of the mechanisms involved in preservation of ancestral haplotypes, it is clear that these haplotypes carry several MHC genes, other than HLA, which may be relevant to antigen presentation, autoimmune responses, and transplantation rejection. In light of the existence of ancestral haplotypes, it is critical to evaluate MHC associations with disease and transplantation outcome in terms of associations with ancestral haplotypes rather than individual alleles.

Alleles↗
PubMed1978

Comparison of the haplotypes of the major histocompatibility complex in the rat. III. Two difficult haplotypes: H-1h (Ag-B12) in the HW strain and Ag-B13 (H-1m) in the MNR/N strain.

Two haplotypes which posed difficult problems in serological identification, those of the HW and MNR/N strains, were studied. The HW strain was originally described as a unique haplotype (H-1h), but breeding difficulties precluded its detailed serological analysis. The red blood cells of the HW strain agglutinate weakly and cross-react with antisera to the Ag-B8 group. Anti-HW antisera cross-react strongly with LEW, ACI and WKA, but absorption with these strains did not produce an adequate typing serum. By judicious selection of recipients, however, an appropriate typing reagent could be made; a particularly useful one was (BUF X MR)F1 anti-HW absorbed with WKA red blood cells. The HW haplotype segregated appropriately in a (DA X HW)F2 population. The HW strain is a low responder to poly(Glu52Lys33Tyr15). The H-1h haplotype of this strain was designated Ag-B12. The MNR/N strain had not previously been studied serologically, although its MLR type had been defined as H-1c (MLR-5). Antisera to MNR/N cross-reacted strongly with the H-1a,b,d,f haplotypes, but MNR/N red blood cells agglutinated only weakly with many antisera. An operationally monospecific reagent antiserum to the MNR/N haplotype could not be made. The uniqueness of the MNR/N haplotype was shown by F1 tests with LEW.1A, LEW.1D and LEW.1F, by various serological analyses, including production of antisera against MNR/N and in the MR strain; by segregation studies with (LEW X LEW.1D)N5 and (DA X DA.MNR)N4 segregating back-cross populations, and by grafting skin from (DA X DA.MNR)N4 homozygous and heterozygous animals to DA recipients. The MNR/N strain is a high-responder to poly(Glu52Lys33Tyr15). The MNR/N haplotype of this strain was designated Ag-B13 (H-1m). The data led to the working hypothesis that the MNR/N strain may be a recombination between the A region of H-1d and the B region of H-1c. In addition, the H-1d private specificity at the A region was probably lost by a deletion mutation which left the main complex of public specificities intact.

Animals↗
PubMed1977

Comparison of haplotypes of the major histocompatibility complex in the rat. I. The Ag-B7 (H-1g) and Ag-B8 (H-1k) haplotypes.

Two haplotypes of the major histocompatibility complex of the rat, Ag-B7 and Ag-B8, have been compared with known H-1 haplotypes using the F1 skin-graft test and the dextran haemagglutination test. Both of these Ag-B haplotypes were different from the known H-1 haplotypes and determined different private specificities. The Ag-B7 haplotype was denoted as H-1g and the Ag-B8 haplotype as H-1k. The complex structure of the serologically detected antigenic products of these haplotypes was determined by means of H-1 congenic lines.

Alleles↗
PubMed1992

Structural similarity of the HLA-DQ region in DQ3 and DQ4 haplotypes and structural diversity of the HLA-DQ region in HLA-DR7 haplotypes.

Genomic DNA obtained from a B lymphoblastoid cell line was digested with appropriate restriction endonuclease and hybridized with several probes specific for genes encoding HLA-DQ. Southern hybridization with a DQA1 3'untranslated (UT) region probe showed DQ2-type hybridization pattern in DR7DQ3 haplotype. On the contrary, DQB1 3'UT probe showed DQ3-type pattern in the same haplotype. Gene cloning and DNA sequencing analysis revealed a repetitive sequence, (TG)19, between DQA1 and DQB1 gene in the DR7DQ3 haplotype. These results suggest that a recombination event has occurred near this potential Z-DNA structure in the haplotype, DR7DQ3. The 3'UT region probes of DQA1 and DQB1 genes failed to detect restriction fragment length polymorphism (RFLP) differences between DR4DQ3 and DR4DQ4 haplotypes in this experiment, suggesting that the gene structure between DQA1 and DQB1 is conserved in these haplotypes.

Antigenic Variation↗
PubMed1992

Ancestral haplotypes carry haplotypic and haplospecific polymorphisms of BAT1: possible relevance to autoimmune disease.

The human BAT1 gene, located in the central MHC region (approximately 170 kb centrometric of HLA-B), is polymorphic and the polymorphism correlates with MHC ancestral haplotypes. Allelic RFLP patterns have been assigned to several ancestral haplotypes and have been shown to be 'haplotypic' (i.e. found on all examples of the same ancestral haplotype) and in some cases 'haplospecific' (i.e. unique to one ancestral haplotype). The relevance of the BAT1 polymorphism to susceptibility to Myasthenia Gravis (MG) has been investigated. The frequency of the BAT1 B allelic pattern is increased in patients with MG (n = 16) compared to an equal number of control subjects. The increase is due to the association between MG and the 8.1 ancestral haplotype (HLA A1, Cw7, B8, BfS, C4AQ0, C4B1, DR3, DQw2).

Autoimmune Diseases↗
PubMed1977

Comparison of haplotypes of the major histocompatibility complex in the rat. II. Serological analysis of the haplotypes H-1a (Ag-B4), H-1d (Ag-B9) and H-1f (Ag-B10).

The strongly cross-reacting haplotypes of the inbred strains DA, ACI, ACP, MR, BD V and AS2, and of the congenic lines LEW.1A, LEW.1D and LEW.1F, were explored. All of these inbred strains and these congenic lines type with anti-Ag-B4 antisera raised against the DA strain, which behaved as operationally mono-specific in previously reported studies of the eight currently defined Ag-B haplotypes. Serological analyses showed that this cross-reactivity was due to antibodies against public antigenic specificities which were not previously recognized as being in the anti-Ag-B4 antisera, due to the fact that the LEW.1D and LEW.1F animals were not available for testing. With the use of appropriate antisera and of absorption studies, two haplotypes in the H-1 system were found not to have been previously identified in the Ag-B system. The animals carrying the H-1d haplotype (MR, BD V and LEW.1D) have been designated as Ag-B9, and those carrying the H-1f haplotype (AS2 and LEW.1F) have been designated as Ag-B10. With the proper absorptions, an anti-Ag-B4 antiserum can be prepared which reacts only with the DA, ACI and ACP strains, and it will henceforth be used as the operationally mono-specific Ag-B4 typing reagent. A variety of typing experiments showed that the results using antisera raised in Pittsburgh and in Prague and using the Ficoll and dextran haemagglutination methods were the same.

Alleles↗
PubMed1979

Comparison of the haplotypes of the major histocompatibility complex in the rat. IV. The six original Ag-B haplotypes.

The six original haplotypes described in the Ag-B system were compared with their counterparts in the H-1 system. Antisera to the Ag-B haplotypes raised in inbred rats and antisera to H-1 haplotypes raised in congenic lines were tested against various panels of cell from inbred and congenic lines by the dextran and Ficoll haemagglutination methods. The private and strong public specificities detected in both systems were the same, but there were some minor differences in the intermediate and weak reactivities detected. The cross-reactivity of the antisera raised in inbred rats was broader than that of antisera raised in congenic lines. The identity of the antigenic products detected in the two systems by the dextran and Ficoll tests was further confirmed by a variety of absorption analyses and by F1 tests. This study completes the systematic serological comparison of the haplotypes of the major histocompatibility complex of the rat described originally in the Ag-B and H-1 systems.

Animals↗
PubMed2025

β1- and β2-adrenergic Receptor Haplotypes Regulate Therapeutic Responses to Placebo and the Biased Ligand β-blocker Bucindolol.

BACKGROUND: ADRB1 and ADRB2, encoding cardiac myocyte &#x3b2;1- and &#x3b2;2-adrenergic receptors (ARs) that mediate pathologic myocardial remodeling in response to chronically increased signaling, contain N-terminus haplotype variants capable of influencing agonist- or biased ligand-induced receptor internalization that uncouples canonical signaling and initiates EGFR/ERK1/2 cardioprotection. METHODS: In two heart failure (HF) clinical trial genetic substudies we investigated effects of internalizing vs. internalization-resistant ADRB1/ADRB2 haplotypes on clinical or biomarker responses to the biased ligand &#x3b2;-blocker bucindolol vs. placebo or vs. the nonbiased &#x3b2;1-antagonist metoprolol, and in haplotyped isolated human heart preparations we measured ERK1/2 activation in response to these same interventions. RESULTS: In subjects with &#x2265;3 internalizing ADRB1+ADRB2 haplotypes (6.7% subcohort) placebo treatment was associated with fewer clinical events compared to subjects with internalization-resistant haplotypes (Odds Ratio (OR) 0.28, 95% CI (0.10, 0.82)). In contrast, placebo treatment in subjects with &#x2265;3 internalization-resistant haplotypes (70% subcohort) was associated with more clinical events in comparison to subjects with internalizing haplotype counterparts (OR 1.64 (1.46, 1.84)). Bucindolol treatment was equal to placebo in the &#x2265;3 internalizing subcohort, but was superior to placebo in the internalization-resistant subcohort (bucindolol vs. placebo OR 0.49 (0.41, 0.58)). In subjects with all 4 haplotypes internalization-resistant (25% subcohort), bucindolol vs. placebo reduced time to first event rates by 62.3&#xb1;17.5% (P <0.01, 1.68&#xb1;0.34 fold > the all-haplotypes parent population and additive to 1.92&#xb1;0.58 fold when the ADRB1 haplotype contained Arg389 rather than Gly389). The same bucindolol vs. placebo pattern was observed for NT-proBNP or norepinephrine reduction vs. metoprolol. In these comparisons ADRB2 and ADRB1 haplotypes behaved similarly, and although the haplotypes differed in frequency between Black and non-Black subjects, within haplotypes there were no by-race differences in therapeutic effects. Bucindolol but not metoprolol activated ERK1/2 signaling in isolated ventricular preparations with &#x2265;3 internalization-resistant haplotypes. CONCLUSIONS: 1) Both &#x3b2;1- and &#x3b2;2-AR haplotypes regulate therapeutic responses in HF; internalizing species confer protection against clinical events in placebo-treated subjects, while in internalization-resistant haplotypes the biased ligand &#x3b2;-blocker bucindolol but not the non-biased ligand metoprolol is associated with favorable effects. 2) The biased ligand cardioprotective effect may be related to internalization-dependent or -independent ERK1/2 activation.

Beta Adrenergic Receptors↗
PubMed1992

Polymorphisms distinguishing different mouse species and t haplotypes.

Three anonymous chromosome 17 DNA markers, D17Tu36, D17Tu43, and D17Le66B, differentiate between house mouse species and/or between t chromosomes. The D17Tu36 probe, which maps near the Fu locus and to the In(17)4 on t chromosomes, identifies at least 15 haplotypes, each haplotype characterized by a particular combination of DNA fragments obtained after digestion with the Taq I restriction endonuclease. Ten of these haplotypes occur in Mus domesticus, while the remaining five occur in M. musculus. In each of these two species, one haplotype is borne by t chromosomes while the other haplotypes are present on non-t chromosomes. The D17Tu43 probe, which maps near the D17Leh122 locus and to the In(17)3 on t chromosomes, also identifies at least 15 haplotypes in Taq I DNA digests, of which nine occur in M. domesticus and six in M. musculus. One of the nine M. domesticus haplotypes is borne by t chromosomes, the other haplotypes are borne by non-t chromosomes; two of the six M. musculus haplotypes are borne by t chromosomes and the remaining four by non-t chromosomes. Some of the D17Tu43 haplotypes are widely distributed in a given species, while others appear to be population-specific. Exceptions to species-specificity are found only in a few mice captured near the M. domesticus-M. musculus hybrid zone or in t chromosomes that appear to be of hybrid origin. The D17Leh66B probe, which maps to the In(17)2, distinguishes three haplotypes of M. domesticus-derived t chromosomes and one haplotype of M. musculus-derived t chromosomes. Because of these characteristics, the three markers are well suited for the study of mouse population genetics in general and of t chromosome population genetics in particular. A preliminary survey of wild M. domesticus and M. musculus populations has not uncovered any evidence of widespread introgression of genes from one species to the other; possible minor introgressions were found only in the vicinity of the hybrid zone. Typing of inbred strains has revealed the contribution of only M. domesticus DNA to the chromosome 17 of the laboratory mouse.

Animals↗
PubMed1992

Sequence differences between HLA-B and TNF distinguish different MHC ancestral haplotypes.

The HLA-B locus is extremely polymorphic. We have sequenced a region, CL, telomeric of HLA-B that also shows a high degree of allelic variation which we have shown previously by RFLP analysis. The polymorphism can be accounted for by sequence variation in duplicated, reiterated sequence elements called geometric elements. Comparison of the CL1 and CL2 sequences from the 57.1, 8.1, 18.2 and 7.1 ancestral haplotypes revealed that the lengths of the elements vary, both between the duplicated loci within a haplotype and between haplotypes, apparently because certain sequences are inserted or deleted. It is possible, using the polymerase chain reaction, to amplify these elements in genomic DNA from ancestral haplotypes for which sequence data of the CL region are not available and to obtain gel patterns which are characteristic of different ancestral haplotypes. The most striking feature of the data is the fact that the majority of the CL patterns are haplospecific; i.e. have a particular pattern that is unique for a particular ancestral haplotype and can be used to type these ancestral haplotypes. At least 12 different allelic patterns have been identified within a panel of 29 cell lines representing 16 ancestral haplotypes. For these 16 ancestral haplotypes, all examples of each haplotype have the same CL pattern. The haplotypic nature of the patterns confirms that ancestral haplotypes are conserved chromosomal segments and that coding and non-coding sequences are identical by descent from a remote ancestor.

Base Sequence↗
PubMed1992

Linkage disequilibrium between phenylketonuria and RFLP haplotype 1 at the phenylalanine hydroxylase locus in Portugal.

RFLPs of 36 normal and 41 mutant alleles at the phenylalanine hydroxylase locus were determined in 31 Portuguese kindreds. A total of 14 haplotypes including 10 normal and 7 mutant alleles were observed. Almost 75% of all mutant alleles were confined within only two haplotypes, namely haplotype 9 (17.1%) and haplotype 1 (56.1%). This frequency of mutant haplotype 1 in Portugal is, to our knowledge, the highest for this mutant haplotype in all studies reported to date. Other mutant haplotypes were either rare (haplotype 2, 9.7%) or totally absent (haplotype 3, 0%). Only 24.5% of all mutant alleles were found to consistently carry identified mutations, particularly R261Q (9.8%), R252W (3.3%), R408W (1.6%) and delta I94 (3.3%). A new mutation, L249F, located in the seventh exon of the gene, accounted for 6.5% of all mutant alleles in our series. Interestingly, this mutant genotype was consistently associated with mutant haplotype 1 (P less than 0.01), as also observed for the R261Q mutation. It appears, therefore, that mutant haplotype 1 is genotypically heterogeneous in Portugal and that more than two mutations account for its prevalence in this country.

Alleles↗
PubMed2025

Large Haplotypes Linked to Climate and Life History Variation in Divergent Lineages of Atlantic Salmon (Salmo salar).

Advances in sequencing are revealing that linked genomic architectures, enabling the evolution of co-adapted alleles at multiple loci, often shape complex phenotypes. Several recent studies have identified such architectures (e.g., chromosomal rearrangements and supergenes) contributing to adaptation or divergence across diverse species, from plants to mammals. Specifically, within Atlantic salmon (Salmo salar ), genomic studies are revealing large haplotypes and structural variants that may underpin local adaptation in the species. Using data from >&#x2009;4000 individuals from 134 locations spanning the North Atlantic Ocean, we identify a large (~3&#x2009;Mbp) genomic region on Ssa18 showing patterns of differentiation and linkage disequilibrium (LD) indicative of a large haplotype block containing three divergent haplotypes (herein A, B and C haplotypes). In Europe, haplotypes A and B were common, whereas A and C were more common within North America, suggesting a shared 'ancestral' A haplotype, with different continent-specific alternative haplotypes. Data support independent origins of divergent haplotypes in each continent, as well as signals of trans-oceanic introgression of haplotypes. Haplotype frequency is strongly associated with latitude, climate and life history (smolt age); however, the strength and direction of these relationships vary across continents. Overall, our analyses were consistent with other studies that identify chromosomal rearrangements; however, long-read sequence data did not find evidence of a structural variant, and instead an ancestral fusion may explain the formation and maintenance of the observed haplotypes. Our study contributes to ongoing efforts to understand the evolutionary role of linked genomic architecture in Atlantic salmon and its significance in salmonid diversification.

Climate Change↗
PubMed1992

A unique recombination event resulting in a C4A*Q0,C4B*Q0 double null haplotype.

The fourth component of complement (C4) is encoded by two closely linked genes (C4A and C4B) within the MHC. Null alleles at either locus (C4AQ0 or C4BQ0) are relatively common, occurring at the C4A locus in approximately 10% of normal individuals and at the C4B locus in approximately 16% of normal individuals. However, the presence of the double null haplotype (C4A*Q0,B*Q0) on the same chromosome is extremely rare. We recently studied a 7-yr-old patient with recurrent sinopulmonary infections in whom we documented the mechanism by which the C4A*Q0,B*Q0 double null haplotype arose. Evaluation revealed significantly reduced levels of both C4 antigen and C4 hemolytic activity. Analysis of extended haplotypes in the family was performed using MHC typing and genomic DNA analysis. The patient was found to have a C4A*3,B*Q0 haplotype and a C4A*Q0,B*Q0 haplotype. The C4A*3,B*Q0 haplotype was contributed by the father. The mother possessed a C4A*Q0,B*1 haplotype and a C4A*3,B*1 haplotype. The first maternal haplotype was involved in a recombination event within the C4B locus on her other chromosome and resulted in a new C4B*Q0 null allele and the patient's C4A*Q0,B*Q0 haplotype. Segregation analysis mapped the recombination to a region 3' to the unique 6.4-kb TaqI restriction fragment of the maternal C4B locus. This is the first demonstration of a recombination event producing a C4 double null haplotype.

Blotting, Southern↗
PubMed1992

A high frequency of the A30, B18, DR3, DRw52, DQw2 extended haplotype in Sardinian celiac disease patients: further evidence that disease susceptibility is conferred by DQ A1*0501, B1*0201.

This study characterizes by serological and molecular methods the HLA class I and class II alleles in a group of celiac disease children, their parents and a control group of Sardinian descent. We found the DR3-DQw2 haplotype in all patients which was, in almost all cases (84%), associated with the HLA-A30, B18, DR3, DRw52, DQw2 extended haplotype named "Sardinian haplotype" because of its frequency (12-15%) in this Caucasian population. This is the first time that this DQw2-linked haplotype has been reported with such a high frequency in CD. However, no different distribution of "Sardinian haplotype" was found comparing CD patients with 91 haplotyped DQw2-positive controls. This finding indicates that the DQw2 antigen in Sardinians is almost always associated with the A30, B18, DR3, DRw52, DQw2 extended haplotype. The DQA1 and DQB1 second exon sequence analysis of the B18,DR3 and B8,DR3 haplotypes showed the DQA1*0501 and DQB1*0201 alleles which shared the already published sequences. DPB1 subtyping showed the DPB1*0301 allele more frequently (p less than 0.005) in CD patients but this difference was no longer significant when patients and controls, both heterozygous for the DR3-DQw2 haplotype, were compared. We suggest that the divergent HLA extended haplotypes and DP allele associated with CD, described in different Caucasian populations, can be explained by the particular DQw2 linkage disequilibrium in each population.

Adult↗
PubMed1992

HLA haplotypes in type 1 (insulin-dependent) diabetes mellitus: molecular analysis of the HLA-DQ locus. The DIME Study Group.

In Caucasians the predisposition to Type 1 (insulin-dependent) diabetes mellitus has been shown to associate with HLA-DR3,DQw2 and DR4,DQw8 and with the presence of amino acids other than aspartic acid at position 57 on the HLA-DQ beta chain. In Finland the haplotype-specific absolute risk for developing Type 1 diabetes differs between various DR3 and DR4 positive haplotypes. The aim of our present analysis was to find out whether this variation is attributable to polymorphism at the DQ locus. As part of a nationwide prospective study including 757 serologically HLA genotyped families, we determined HLA-DQ alpha and DQ beta restriction fragment polymorphisms in 17 selected families with important susceptibility haplotypes. Additionally, the DQA1 alleles were determined from 19 haplotypes using sequence-specific oligonucleotide probes, and the DQB1 second exon was sequenced from nine haplotypes. The DR3 as well as DR4 positive haplotypes frequently found in Type 1 diabetic patients showed no variation at the HLA-DQ locus, and they were DQw2 and DQw8, respectively. The absolute risk for Type 1 diabetes for DR4,DQw8 positive haplotypes A2,Cw4,Bw35,DR4 A3,Cw3,Bw62,DR4, A24,Cw7,Bw39,DR4, A2,Cw3,Bw62, DR4, and A2,Cw1,Bw56,DR4 was 35/100,000, 130/100,000, 166/100,000, 196/100,000, and 218/100,000, respectively. The absolute risks for DR3,DQw2 positive haplotypes A1, Cw7,B8,DR3 and A2,Cw7,B8,DR3 were 68/100,000 and 103/100,000, respectively. These results provide further evidence that not only the polymorphism at the DQ locus but also other genes of the haplotypes contribute to susceptibility to Type 1 diabetes.

Adolescent↗