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PubMed2006

Haplotypes in cathechol-O-methyltransferase gene confer increased risk for psychosis in Alzheimer disease.

BACKGROUND: The gene encoding catechol-O-methyltransferase (COMT) has been suggested as a candidate for Alzheimer-related psychosis (AD-P) susceptibility, and an association between AD-P and a functional valine to methionine polymorphism has been reported. OBJECTIVE: The aim of this study was to assess the genetic contribution of other COMT variants to the risk of AD-P. METHODS: Two hundred and forty-six AD patients underwent clinical and neuropsychological examination as well as an evaluation of behavioural and psychiatric disturbances. They were subsequently divided into two subgroups according to the presence (AD-P) or the absence (AD-nP) of psychotic symptoms. Four single-nucleotide polymorphisms (SNPs) within COMT gene were evaluated, i.e. rs737865, rs737864, intron 1 C2754delC, and the well-known valine/methionine variant (rs4680). Analyses were performed on the single locus and pairwise disequilibrium of loci, and multi-locus haplotype. RESULTS: The individual SNP analysis confirmed an association for the valine/methionine variant with AD-P. Haplotype analyses revealed that the alleles at four loci (rs737865, rs737864, intron 1 C2754delC, rs4680) interacted to create the risk of psychosis in AD, as A-C-C-G haplotype (OR=2.08, 95% CI=1.02-4.27, P=0.044) and G-C-delC-G haplotype (OR=2.54, 95% CI=1.32-4.90, P=0.006) in respect to the most common and not-at-risk A-C-C-A haplotype which was significantly overrepresented in AD-P. CONCLUSIONS: The present findings provide evidence of COMT genetic variations' role in the susceptibility to AD-related psychosis. The observation of a haplotype effect of different polymorphisms within the COMT gene puts emphasis on the usefulness of haplotype analysis in better defining individualized genetic risk profiles in AD.

Aged↗

PubMed2004

ADLAPH: A molecular haplotyping method based on allele-discriminating long-range PCR.

We present a method, called Allele-Discriminating Long and Accurate PCR Haplotyping (ADLAPH), for directly determining haplotypes from an extended genomic region. This method uses allele-discriminating primers in long-range PCR to amplify only one of the two chromosome homologues for the region of interest. Haplotypes are then determined from these phase-separated PCR fragments by conventional single nucleotide polymorphism (SNP) genotyping methods. This simple robust procedure makes it practical for high-throughput haplotyping of unrelated individuals, and potentially allows direct observation of haplotype information for up to 40 kb or more. We demonstrate the feasibility of this molecular haplotyping procedure by generating apolipoprotein E (APOE) haplotypes from 100 unrelated subjects.

Alleles↗

PubMed2006

SNP identification, linkage disequilibrium, and haplotype analysis for a 200-kb genomic region in a Korean population.

Understanding patterns of linkage disequilibrium (LD) across genomes may facilitate association mapping studies to localize genetic variants influencing complex diseases, a recognition that led to the International Haplotype Mapping Project (HapMap). Divergent patterns of haplotype frequency and LD across global populations require that the HapMap database be supplemented with haplotype and LD data from additional populations. We conducted a pilot study of the LD and haplotype structure of a genomic region in a Korean population. A total of 165 SNPs were identified in a 200-kb region of 22q13.2 by direct sequencing. Unphased genotype data were generated for 76 SNPs in 90 unrelated Korean individuals. LD, haplotype diversity, and recombination rates were assessed in this region and compared with the HapMap database. The pattern of LD and haplotype frequencies of Korean samples showed a high degree of similarity with Japanese data. There was a strong correlation between high LD and low recombination frequency in this region. We found considerable similarities in local LD patterns between three Asian populations (Han Chinese, Japanese, and Korean) and the CEPH population. Haplotype frequencies were, however, significantly different between them. Our results should further the understanding of distinctive Korean genomic features and assist in designing appropriate association studies.

Asian People↗

PubMed2001

Two families from New England with usher syndrome type IC with distinct haplotypes.

PURPOSE: To search for patients with Usher syndrome type IC among those with Usher syndrome type I who reside in New England. METHODS: Genotype analysis of microsatellite markers closely linked to the USH1C locus was done using the polymerase chain reaction. We compared the haplotype of our patients who were homozygous in the USH1C region with the haplotypes found in previously reported USH1C Acadian families who reside in southwestern Louisiana and from a single family residing in Lebanon. RESULTS: Of 46 unrelated cases of Usher syndrome type I residing in New England, two were homozygous at genetic markers in the USH1C region. Of these, one carried the Acadian USH1C haplotype and had Acadian ancestors (that is, from Nova Scotia) who did not participate in the 1755 migration of Acadians to Louisiana. The second family had a haplotype that proved to be the same as that of a family with USH1C residing in Lebanon. Each of the two families had haplotypes distinct from the other. CONCLUSION: This is the first report that some patients residing in New England have Usher syndrome type IC. Patients with Usher syndrome type IC can have the Acadian haplotype or the Lebanese haplotype compatible with the idea that at least two independently arising pathogenic mutations have occurred in the yet-to-be identified USH1C gene.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Tau haplotype frequency in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

It has been reported that the H1 haplotype of the tau gene, located on chromosome 17q21, is associated with progressive supranuclear palsy. Recently, it has also been claimed that the H1 haplotype could also be a risk factor for frontotemporal dementia. However, these claims are variable and the involvement of the apolipoprotein E gene as well as the H1 haplotype has been suggested. In light of this we assessed the frequency of tau gene haplotypes in 113 cases of frontotemporal lobar degeneration and 168 control samples. We found a positive association between the H1 haplotype and frontotemporal dementia, but not with any of the other disease groupings (P = 0.029, odds ratio 1.81). We did not observe any affect on age at onset and tau haplotype or apolipoprotein E alleles, nor were any deviation from control frequencies of apolipoprotein E alleles observed. These data are consistent with the hypothesis that the tau gene, or nearby gene on the H1 haplotype, is a risk factor for frontotemporal dementia.

Age of Onset↗

PubMed1996

B-haplotype control of CD4/CD8 subsets and TCR V beta usage in chicken T lymphocytes.

The major histocompatibility (B) complex of the chicken contains genes similar to Class I (B-F) and Class II (B-L beta) genes in mammals, as well as a highly-polymorphic gene family (B-G) whose exact function is not known. Specific B-haplotypes are strongly associated with resistance to a number of infectious diseases, and with immune responses to soluble and cellular antigens. In mammals, Class I and Class II molecules control development of the T cell repertoire, including selection of CD4+ and CD8+ T cells. One study of chickens reported that low CD4:CD8 ratio was associated with the B4 haplotype, which shares expressed B-F/B-L genes with the B13 haplotype. In studies reported here, chickens of two haplotypes carried in the Auburn R line, B302 and B305 (which is B13-related), were evaluated for percentages of T cells expressing the CD4, CD8, CD3, TCR1, TCR2 and TCR3 antigens in peripheral blood lymphocytes (PBL), thymus, and spleen. These two haplotypes were chosen for comparison because they differ in resistance to Marek's disease (MD) and are closely-related in B-F and B-L genes by restriction fragment length polymorphism analyses. Homozygous birds of each B haplotype were produced from crosses of (B302 x B305)F1 sires and dams. PBL, thymocytes, and splenocytes from B302 homozygotes had higher CD4:CD8 ratios than B305 homozygotes. However, CD4:CD8 ratio differences could not be attributed to haplotype-controlled differences in V beta usage within CD4/CD8 subsets, as has been described for certain V beta families in mice and humans. These results indicate that thymic selection events involving CD4 and CD8 subsets and TCR V beta usage are controlled by a gene or genes closely-linked to the B-complex, which may or may not be Class I or Class II genes.

Animals↗

PubMed2000

MHC class I and class II phenotype, gene, and haplotype frequencies in Greeks using molecular typing data.

In the present study, DNA typing for HLA-A, C, B, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, and DPB1 was performed for 246 healthy, unrelated Greek volunteers of 20-59 years of age. Phenotype, genotype frequencies, Hardy-Weinberg equilibrium fit, and 3-locus haplotype frequencies for HLA-A, C, B, HLA-A, B, DRB1, HLA-DRB1, DQA1, DQB1, and HLA-DRB1, DQB1, DPB1 were calculated. Furthermore, linkage disequilibrium, deltas, relative deltas and p-values for significance of the deltas were defined. The population studied is in Hardy-Weinberg equilibrium, and many MHC haplotypes are in linkage disequilibrium. The most frequent specificities were HLA-A*02 (phenotype frequency = 44.3%) followed by HLA-A*24 (27.2%), HLA-B*51 (28.5%), HLA-B*18 (26.8%) and HLA-B*35 (26.4%) and HLA-Cw*04 (30.1%) and HLA-Cw*12 (26.8%). The most frequent MHC class II alleles were HLA-DRB1*1104 (34.1%), HLA-DQB1*0301 (54.5%) and HLA-DPB1*0401 with a phenotype frequency of 59.8%. The most prominent HLA-A, C, B haplotypes were HLA-A*24, Cw*04, B*35, and HLA-A*02, Cw*04, B*35, each of them observed in 21/246 individuals. The most frequent HLA-A, B, DRB1 haplotype was HLA-A*02, B*18, DRB1*1104 seen in 20/246 individuals, while the haplotype HLA-DRB1*1104, DQB1*0301, DPB1*0401 was found in 49/246 individuals. Finally, the haplotype DRB1*1104, DQA1*0501, DQB1*0301 was observed in 83/246 individuals. These results can be used for the estimation of the probability of finding a suitable haplotypically identical related or unrelated stem cell donor for patients of Greek ancestry. In addition, they can be used for HLA and disease association studies, genetic distance studies in the Balkan and Mediterranean area, paternity cases, and matching probability calculations for the optimal allocation of kidneys in Greece.

Adult↗

PubMed2001

Antigen, allele, and haplotype frequencies report of the ASHI minority antigens workshops: part 1, African-Americans.

HLA typing was performed on 977 African Americans residing throughout most of the United States. Class I and class II antigens and class II alleles were defined for all individuals and class I alleles were determined for a subset of individuals. The occurrence of 854 of the individuals in family groups permitted direct counting of allele and haplotype frequencies. The data were analyzed for antigen, allele, and haplotype frequencies; recombination frequencies; segregation distortion; distribution of haplotype frequencies; linkage disequilibria; and geographic distribution of DR antigens. Tables of the antigen, allele, the most common two and three point haplotypes, and 88 extended haplotypes that include class I and class II alleles are presented. Notable findings include a lower than expected frequency of recombination between the B and DR loci (theta= 0.0013), lower than expected frequency of inheritance (44.5% vs 54.5%) of the DRB1*1503; DQB1*0602 haplotype, lower than anticipated linkage disequilibrium values for DR; DQ haplotypes, and a skewed geographic distribution of DR antigens.

Alleles↗

PubMed2003

Grouping of Y-STR haplotypes discloses European geographic clines.

Y-STR haplotypes are widely studied in Europe and an extensive databasing effort has been conducted (http://www.ystr.org). The distribution of these haplotypes has been considered to present no evidence for substructure at central and southern European level. This picture contrasts with the one that results from Y haplogroups defined by binary markers. This paradox has been solved by admitting that the high STR mutation rate and corresponding recurrence has erased geographic structuration. This explanation prompted us to reanalyse Y-STR haplotypes distribution bearing in mind the commonly admitted model for the generation of diversity in these markers, namely the stepwise mutation model (SMM) and, thus, taking the molecular distance between haplotypes into consideration. Accordingly, we have studied the European distribution of the two most frequent haplotypes in the Iberian Peninsula and their one step neighbours using the European samples deposited in the Y STR database (http://www.ystr.org). For the first group we found a clear-cut decreasing W-E gradient, while for the second the highest frequencies were found in the Iberian Peninsula (3.98% in Portugal and 3.85% in Spain), dropping to 2.88% in France and showing a less well defined SW-NW gradient. Furthermore, we have tested the agreement between haplotype groups and binary markers haplogroups in a random sample of 292 individuals from Northern Portugal. Our results demonstrate that (a) Y-STR haplotype data can be used for wide-scale anthropological approaches disclosing information that has been considered only available through binary markers and (b) forensic use of continental databases needs careful refinement, due to the macro-geographic pattern now evidenced.

Chromosomes, Human, Y↗

PubMed2001

Association and excess of transmission of a DRD2 haplotype in a sample of French schizophrenic patients.

The gene which codes for dopamine receptor D2 (DRD2) is considered as one of the most relevant candidate genes in schizophrenia. Previous genetic studies focusing on this gene gave conflicting results, potentially because of the differences in methodology (linkage versus association studies), and the different loci analyzed (the DRD2 gene having many polymorphisms). We used a progressive strategy with three different approaches (case/control, haplotype relative risk and transmission disequilibrium test) and investigated two genetic polymorphisms (TaqI B1/B2 and TaqI A1/A2, spanning the coding region of the DRD2 gene) in 50 patients with DSM-IV diagnoses of schizophrenia, in their 100 parents and in 50 healthy, matched controls. Firstly, we found a significant excess of the two alleles (B2 and A2) in the schizophrenic group compared to unaffected controls. Secondly, we found an excess of transmission from the parents to their affected children, using the haplotype relative risk design applied to the B2A2 haplotype. Finally, the transmission disequilibrium test showed evidence for linkage between B2A2 haplotype and schizophrenia. The significant excess of the B2A2 haplotype in schizophrenic patients is specifically observed in a subsample of patients with a disease onset occurring after 20 years of age. As the haplotype contains nearly the entire DRD2 gene, we found convergent evidence in our sample for a significant role of the DRD2 gene in the risk for schizophrenia. This haplotype may be more specifically involved in the disorder's onset at a later age in some patients, or, alternatively, may be implicated as a modifying factor acting on age of onset.

Adult↗

PubMed2002

The probability that similar haplotypes are identical by descent.

The logic of gene mapping in highly penetrant diseases is to find the minimal overlap of haplotypes that are identical by descent (IBD). If the pedigree is unknown, identity by descent of haplotype overlap cannot be established with certainty. In many cases, it is intuitively clear that similar haplotypes are indeed IBD. The logical and statistical evaluation of haplotype overlap requires that probabilities of IBD are substantial. It is, therefore, important to estimate these probabilities. In this paper, we derive a recursive formula for the probability of IBD. Simulations are used to validate the expected values and to study the variability around the expected value. We demonstrate that for populations 1000 generations of age - without bottlenecks - haplotypes of 1 cM consisting of at least five microsatellite markers have a significant probability to be IBD. Likewise, SNP haplotypes of 1 cM should consist of at least nine identical SNP alleles for a similar probability of IBD. Without considering bottlenecks, haplotypes consisting of as few as three SNPs spanning a region of less than 0.01 cM are likely IBD in populations that are 10000 generations of age.

Chromosome Mapping↗

PubMed1990

Search for differences among t haplotypes in distorter and responder genes.

Transmission ratio distortion due to the mouse t complex is though to be due to harmful effects of trans-acting distorter genes acting on a responder, with the t complex form of the responder being relatively resistant to this harmful action of the distorters. Previous work had indicated that naturally occurring t haplotypes differed in their responders or in distorters lying near the responder, with the result that animals doubly heterozygous for two responder-carrying haplotypes transmitted these haplotypes unequally. In the present work t haplotypes could be divided into three types on the basis of their transmission when doubly heterozygous with the responder-carrying partial haplotype tlowH. The majority, t0, t6, tw1, tw2 and tw73, were transmitted equally with tlowH, a second group, including tw5 and two haplotypes derived from it, were transmitted less frequently than tlowH, and the single member of a third group, tw32, was transmitted in excess of tlowH. This last result suggests that the underlying differences are in the responder itself, rather than in the distorters. Search for differences among t haplotypes in distorters produced some equivocal results possibly resulting from effects of genetic background. In particular, results of others suggesting presence of a fourth distorter, Tcd-4, were not confirmed.

Animals↗

PubMed1995

The cellular basis for interaction of sterility factors in the mouse t haplotype.

The t haplotypes are variant forms of the proximal one-third of chromosome 17 in the mouse. They contain four inversions (relative to the wildtype DNA) extending over most of this region and house a number of male sterility factors. Males carrying two complete t haplotypes (t/t) are sterile, as are males homozygous for S2, the sterility factor located in the most distal (relative to the centromere) inversion. Males homozygous for the sterility factor S1, located in the most proximal inversion, are not sterile; however, if such a male also is heterozygous for other sterility factors, then sterility results. It has been suggested therefore that homozygosity for S1 enhances the detrimental action of other sterility factors. Sperm from t/t males have severe motility defects and are unable to penetrate investment-free eggs, while sperm from fertile t/+ mice have less serious motility defects and exhibit a delay in penetration of investment-free eggs. To determine whether homozygosity for S1 enhances the cellular defects exhibited by sperm from mice heterozygous for other sterility factors, we compared the motility and egg-penetrating ability of sperm from fertile mice homozygous for S1 to that of sperm from mice carrying one complete t haplotype and one proximal or distal partial t haplotype. The data suggest that sperm from males carrying a proximal partial t haplotype and a complete t haplotype have serious defects in motility and penetration of the investment-free egg, and support the hypothesis that S1 enhances the detrimental effects of other sterility factors within the t haplotype.

Animals↗

PubMed2004

Identification of a cryptic lethal mutation in the mouse t(w73) haplotype.

t haplotypes are naturally occurring, variant forms of the t complex on mouse chromosome 17, characterized by the presence of four inversions with respect to wild-type. They harbour mutations causing male sterility, male transmission ratio distortion (TRD) and embryonic lethality. Mice carrying t haplotypes have been found throughout the world, and genetic studies of the lethal mutations have identified at least 16 complementation groups. The embryonic lethal phenotypes of many t haplotypes have been characterized in detail, and are thought to be the consequence of homozygosity for single gene mutations. However, the existence of additional mutations in genes that function at later stages of development would be obscured. Here we investigated the possibility of multiple mutations in t haplotypes by screening the t(w73) haplotype for the presence of novel mutations. Since genetic analysis of t haplotype mutations is hindered by recombination suppression due to the inversions, deletion complexes covering the proximal two-thirds of the t complex were used to uncover the presence of any new lethal alleles. This analysis revealed a novel mutation between D17Jcs41 and D17Mit100, causing mice carrying both t(w73) and selected deletions to die at birth, prior to feeding. The finding of a new, cryptic lethal mutation in t haplotypes is an indication that these recombinationally isolated chromosomes, which already contain at least one lethal mutation that prevents homozygosity, may serve as sinks for the accumulation of additional recessive mutations.

Alleles↗

PubMed2002

IL-4 receptor alpha chain genetic polymorphism and total IgE levels in the English population: two-locus haplotypes are more informative than individual SNPs.

The IL-4RA locus encodes for the alpha chain of the IL-4 receptor, and is both a functional and positional candidate gene for atopy and allergic disease. Recently Ober et al. have shown that the study of haplotypes at multiple loci in the IL-4RA gene could be more informative than the separate study of single nucleotide polymorphisms (SNPs). One hundred and fifty subjects affected by atopic asthma and 150 healthy control subjects were studied in the English population (Oxford district). Subjects and controls were genotyped for the Ile50Val, Ser478Pro and Gln551Arg polymorphism of the IL-4 receptor alpha chain. The distribution of haplotypes 50-478 shows a highly significant association with IgE levels. In particular, the haplotype Val50/Pro478 is much less frequent in subjects with IgE levels > 100 U mL-1 than in those with IgE levels < 100 U mL-1. Furthermore, the distribution of haplotype 50-551 shows a weak association with IgE levels that is lacking for 478-551 haplotypes. A lower frequency of the Val50/Pro478 haplotype is also observed among asthmatic subjects as compared to healthy controls. With regard to individual SNPs (50 478 and 551), no significant association has been observed with IgE levels or with asthma, thus confirming the higher informative value of the haplotype analysis as compared to separate study on SNPs.

England↗

PubMed2001

The distribution of HLA class II susceptible/protective haplotypes could partially explain the low incidence of type 1 diabetes in continental Italy (Lazio region).

HLA class II is the primary susceptibility gene to type 1 diabetes and the analysis of HLA class II association could help to clarify the relative weight of genetic contribution to the incidence of the disease. Here we present an extensive typing for HLA class II alleles and their haplotypes in a homogenous population of type 1 diabetic patients (n=134) and controls (n=128) and in simplex (n=100) and multiplex families (n=50) from continental Italy (Lazio region). Among the various haplotypes tested, the DRB1*0301-DQA1*0501-DQB1*0201 was the most frequent found in type 1 diabetic patients and was transmitted in 82% of affected siblings, whereas DRB1*0402-DQA1*0301-DQB1*0302 appeared to have the highest odds ratio (10.4), this haplotype was transmitted in 96.3% of affected siblings, followed by DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0405-DQA1*0301-DQB1*0201, DRB1*0401-DQA1*0301-DQB1*0302 and DRB1*0404-DQA1*0301-DQB1*0302. The following haplotypes showed a significant decreased transmission to diabetic siblings: DRB1*0701-DQA1*0201-DQB1*0303, DR2-DQA1*01-DQB1*0602, DR5-DQA1*0501-DQB1*0301. We suggest that the HLA DR/DQ haplotype/genotype frequencies observed could in part explain the low incidence of type 1 diabetes registered in Lazio region (8.1/100.000/year), for a number of reasons: i) the low frequency, in the general control population, of the most susceptible haplotypes and genotype for type 1 diabetes DRB1*0301-DQA1*0501-DQB1*0201 (14%), and DR4-DQA1*0301-DQB1*0302 (9%) and DRB1*0301-DQA1*0501-DQB1*0201/DR4-DQA1*0301-DQB1*0302 (0.8%) compared to other countries characterised by high incidence rate of the disease, Sardinia and Finland, respectively; ii) a significant lower ratio, in the control population, between the susceptible DRB1*0301-DQA1*0501-DQB1*0201 and the neutral DRB1*0701-DQA1*0501-DQB1*0201 haplotypes compared to the Sardinian population; iii) the high frequency of protection haplotypes/genotypes as the DR5-DQA1*0501-DQB1*0301, and DR5-DQA1*0501-DQB1*0301/DR5-DQA1*0501-DQB1*0301 very common in the control population of Lazio region and the DRB1*1401-DQA1*0101-DQB1*0503 haplotype.

Adolescent↗

PubMed2002

Extensive interbreed, but minimal intrabreed, variation of DLA class II alleles and haplotypes in dogs.

The DLA class II genes in the dog major histocompatibility complex are highly polymorphic. To date, 52 DLA-DRB1, 16 DLA-DQA1 and 41 DLA-DQB1 allelic sequences have been assigned. The aim of this study was to examine the intrabreed and interbreed variation of DLA allele and haplotype frequencies in dogs, and to ascertain whether conserved DLA class II haplotypes occur within and between different breeds. One thousand and 25 DNA samples from over 80 different breeds were DLA class II genotyped, the number of dogs per breed ranging from 1 to 61. DNA sequence based typing and sequence specific oligonucleotide probing were used to characterize dogs for their DLA-DRB1, DQA1 and DQB1 alleles. The high frequency of DLA class II homozygous animals (35%), allowed the assignment of many haplotypes despite the absence of family data. Four new DLA alleles were identified during the course of this study. Analysis of the data revealed considerable interbreed variation, not only in allele frequency, but also in the numbers of alleles found per breed. There was also considerable variation in the number of breeds in which particular alleles were found. These interbreed variations were found in all three DLA class II loci tested, and also applied to the three-locus haplotypes identified. Within this data set, 58 different DLA-DRB1/DQA1/DQB1 three-locus haplotypes were identified, which were all found in at least two different animals. Some of the haplotypes appeared to be characteristic of certain breeds. The high interbreed, and relatively low intrabreed, variation of MHC alleles and haplotypes found in this study could provide an explanation for reports of interbreed variation of immune responses to vaccines, viruses and other infections.

Alleles↗

PubMed1990

HLA extended haplotypes in steroid-sensitive nephrotic syndrome of childhood.

Idiopathic nephrotic syndrome has been postulated to have an immunopathogenic basis. To determine whether steroid-sensitive nephrotic syndrome is associated with greater than expected frequencies of specific extended haplotypes of the major histocompatibility complex, we studied genetic markers (Class I, II, III HLA alleles and glyoxalase I) in 173 subjects in 42 families of patients with nephrotic syndrome of childhood. The single allele, DQW2, was found in 72% of steroid sensitive patients compared with only 35% of the controls (P = 0.003). In half of 32 steroid sensitive, but not 10 steroid resistant, patients, one or both of two specific extended haplotypes (alleles that segregate together) were identified. The first, [HLA-A1, B8, DR3, DRW52, SCO1], occurred in 11 of 64 haplotypes, or 17%, compared to 5% of controls (P = 0.017). The other, [HLA-B44, DR7, DRW53, FC31], occurred in 10 of 64 haplotypes, 16% compared to 3.8% of controls (P = 0.014). Five patients had both haplotypes. Patients with these specific extended haplotypes had a greater frequency of relapses than did those with other haplotypes. These data provide additional support for the hypothesis that steroid-sensitive nephrotic syndrome has an immunogenetic basis.

Blotting, Southern↗