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PubMed2005

Haplotype analysis of killer cell immunoglobulin-like receptor genes in 77 Korean families.

Killer cell immunoglobulin-like receptor (KIR) genes constitute a multigene family whose genomic diversity is achieved through variation in gene content and allelic polymorphism within individual KIR genes. To date, 16 KIR genes and pseudogenes have been identified, and group A and group B haplotypes are characterized by a dominance of genes encoding inhibitory and activating receptors, respectively. In the present study, we have investigated the presence or absence of 16 KIR genes and pseudogenes and subtypes of four genes (3DP1, 3DP1 variant; 2DL1, 2DL1 variant; expressed and nonexpressed variant of 2DL5; full length and deleted form of 2DS4) in 352 members of 77 unrelated Korean families using a PCR-based sequence-specific priming method. KIR haplotypes were determined by segregation analysis. A total of 29 different KIR genotypes and 19 (two group A and 17 group B) haplotypes were identified in 154 parents. The distribution of genotypes, in terms of combination of haplotypes, was AA 55.2%, AB 36.4%, and BB 8.4%. Different from Caucasians, full-length 2DS4 (80.5%) was the predominant subtype of 2DS4 and group A (73.4%) outnumbered group B haplotypes (26.6%). The KIR gene frequencies and the predominance of A haplotypes in Koreans are similar to those in the Japanese.

Gene Frequency↗

PubMed2006

The haplotype structure of the human major histocompatibility complex.

There is great interest in the use of single-nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) analysis to localize human disease genes. The results suggest that the human genome, including the major histocompatibility complex (MHC), consists largely of 5- to 200-kb blocks of sequence fixity between which random recombination occurs. Direct determination of MHC haplotypes from family studies also demonstrates similar-sized blocks, but otherwise gives a very different picture, with a third to a half of Caucasian haplotypes fixed from HLA-B to HLA-DR/DQ (at least 1 Mb) as conserved extended haplotypes (CEHs), some of which encompass more than 3 Mb. These fixed haplotypes differ in frequency both in different Caucasian subpopulations and in Caucasian patients with HLA-associated diseases, complicating disease susceptibility gene localization. The inherent inability of LD analysis to "see" DNA fixity beyond three markers contributes to the failure of SNP/LD analysis to define in detail or even detect CEHs in the MHC and probably elsewhere in the genome. More importantly, the use of statistical analysis, rather than direct haplotype determination and counting, fails to reveal the details of haplotype structure essential for gene localization. Given the oversimplified picture of the MHC (and probably the rest of the genome) provided only by SNP/LD-defined blocks, it is questionable whether this approach will be of great help in disease susceptibility gene localization or identification.

Alleles↗

PubMed2006

Linkage disequilibrium with predisposing DR3 haplotypes accounts for apparent effects of tumor necrosis factor and lymphotoxin-alpha polymorphisms on type 1 diabetes susceptibility.

Tumor necrosis factor (TNF) and lymphotoxin alpha (LT-alpha) are immunomodulators that have been hypothesized to contribute to susceptibility to type 1 diabetes (T1D). Several polymorphisms in the TNF and LT-alpha loci have been extensively studied for T1D association, with conflicting reports. In this study, we examined two TNF variants and one LT-alpha variant for T1D association in 283 Caucasian, multiplex T1D families for which complete human leukocyte antigen (HLA) genotyping data are available. Initially, association with T1D was seen for LT-alpha A1069G (intron A, p=0.011, rs909253) and TNF G(-308)A (p<1x10(-5), rs1800629), but no association was observed for TNF G(-238)A (rs361525). After adjusting the data for linkage disequilibrium (LD) with DRB1-DQB1 haplotypes, however, only one polymorphism, TNF G(-238)A showed significant association with T1D (p<0.006). When HLA-DR3 haplotypes were examined, the A allele of TNF G(-238)A was significantly overtransmitted to affected offspring (p<0.009). Including HLA-B data in the analysis revealed that TNF (-238)A is present exclusively on DR3 haplotypes that also carry HLA-B18. Transmission proportion of B18-DR3 haplotypes did not differ between those with TNF (-238)A and those with TNF (-238)G. Thus, variation at TNF does not affect the T1D risk for B18-DR3 haplotypes, and the apparent association of TNF(-238)A with T1D may simply reflect its presence on a high-risk haplotype.

Diabetes Mellitus, Type 1↗

PubMed2005

TGFbeta1 haplotypes and asthma in Indian populations.

BACKGROUND: Asthma is a complex disorder of the airways of the lungs. TGF-beta1 plays a key role in airway remodeling and asthma by having both proinflammatory and anti-inflammatory activities, making TGFbeta1 an important candidate gene to study. OBJECTIVE: To investigate the association of TGFbeta1 gene polymorphisms with asthma. METHODS: A case-control study was designed for identifying polymorphisms and haplotypes associated with asthma and associated phenotypes. We have verified our results in 2 independent cohorts collected from northern (number of patients, 187; number of controls, 187) and western India (number of patients, 209; number of controls, 190). We measured the serum TGF-beta1 levels of selected individuals and correlated them with genotypes and haplotypes. RESULTS: A novel (CT)n(CA)m repeat polymorphism (BV209662) 24.9 kb upstream of TGFbeta1 was identified. A significant association was seen at the level of alleles and genotypes with asthma in the 2 cohorts studied independently (P < .05). Interestingly, a novel 3-locus haplotype, 23_G_T, was found to be significantly associated with asthma (P = .00001 in cohorts A and B) as well as with higher serum TGF-beta1 level (P = .01). On the other hand, a novel haplotype, 22_G_C, was negatively associated with asthma (P = .00001 for cohorts A and B) and with lower serum TGF-beta1 level (P = .0019). CONCLUSION: This is the first study identifying novel risk and protective haplotypes--23_G_T and 22_G_C, respectively--in the TGFbeta1 gene that are associated with asthma. We also demonstrate the functional significance of these haplotypes with serum TGF-beta1 levels. These results would be valuable in elucidating the role of TGF-beta1 in asthma pathogenesis.

Adult↗

PubMed2006

Endothelial nitric oxide synthase genotype and haplotype are not associated with diabetic retinopathy in diabetes type 2 patients.

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene have been associated with the development of diabetic retinopathy (DR) in patients with type 1 diabetes mellitus (T1DM), but not with T2DM. However, no previous study has analyzed combinations of genetic markers (haplotypes), which can be more informative. We studied three eNOS genetic polymorphisms: a single nucleotide polymorphism in the promoter region (T(-786)C), in exon 7 (Glu298Asp), and a variable number of tandem repeats in intron 4 (b/a) in 103 healthy controls, and in 170 patients with T2DM (without DR, N=114; with DR, N=56). We also examined the association of eNOS gene haplotypes with T2DM and with DR. No differences were found in the frequencies of genotypes and alleles of the three polymorphisms among the three groups of subjects. However, the "C-Glu-b" haplotype was more common in healthy controls (24%) than in T2DM patients (7%) (P=0.0001). Finally, no significant difference in the distribution of eNOS haplotypes frequencies was found when T2DM patients with or without DR were compared (P=0.7372). These findings suggest no association between DR and individual eNOS haplotypes in T2DM patients. The "C-Glu-b" haplotype, however, may have a protective effect against T2DM. Further studies should be conducted to address the molecular basis for such an effect.

Adult↗

PubMed2005

Impact of ABCB1 (MDR1) haplotypes on tacrolimus dosing in adult lung transplant patients who are CYP3A5 3/3 non-expressors.

BACKGROUND: The influence of ABCB1 (MDR1) polymorphisms on tacrolimus dosing has been questioned in previous studies with contradictory findings, possibly due to the association between CYP3A5 polymorphisms and tacrolimus dosing. The objective of this study was to assess the effect of ABCB1 haplotypes from 3 distinct polymorphic sites on the tacrolimus level/dose [L/D] in lung transplant patients limited to CYP3A5 *3/*3 non-expressors. METHOD: A total of 91 lung transplant patients treated primarily with tacrolimus and prednisone were enrolled, and clinical information on drug dosing and blood levels was collected. The [L/D] was calculated for patients receiving tacrolimus at 1, 3, 6, 9 and 12 months post transplant. ABCB1 polymorphisms at C1236T, G2677T, and C3435T were assessed by PCR amplification and DNA sequencing. Haplotypes were estimated by Arlequin ver.2.00. Haplotype effects on tacrolimus [L/D] were assessed by two-way ANOVA. RESULTS: Of the 10 haplotypes, CGC, TTT and CGT accounted for 44.1%, 40.7% and 7.6% of the total haplotypes, respectively. The tacrolimus [L/D] value in the CGC-CGC patients was significantly lower than in patients with CGC-TTT and TTT-TTT genotypes at the first month (mean [L/D]=1.45 versus 3.10 and 3.97 ngxmL(-)(1) /mg/day), and throughout the first post transplant year. CONCLUSION: This study demonstrates that ABCB1 haplotypes derived from three common polymorphisms are associated with tacrolimus dosing in lung transplant patients when eliminating the confounder CYP3A5 genotype.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2005

A haplotype of angiotensinogen gene that is associated with essential hypertension increases its promoter activity in adipocytes.

Obesity is associated with hypertension and other cardiovascular diseases especially in the African-American population. Human angiotensinogen (AGT) gene has seven single nucleotide polymorphisms (SNPs) in 1.2 kb region of its promoter. Recent studies have shown that variant -217A is associated with hypertension in African-American and Chinese population. Nucleotide sequence of the hAGT gene has shown that variant -217A almost always occurs with variants -532T, -793A and -1074T (forming haplotype AAT) and variant -217G almost always occurs with variants -532C, -793G and -1074G (forming haplotype GGG). Since hAGT gene is expressed in the adipose tissue and its expression in this tissue may play a role in hypertension, we have analyzed the role of haplotypes AAT and GGG on the expression of this gene in adipocytes. We show here that a reporter construct with haplotype AAT of the hAGT gene has increased promoter activity on transient transfection in pre-adipocytes and differentiated adipocytes as compared to the reporter construct containing GCGG haplotype. Increased expression of the AGT gene containing haplotype AAT in the liver and adipocytes may be a contributing factor for hypertension.

3T3-L1 Cells↗

PubMed2004

Promoter haplotype combinations for the human PDGFRA gene are associated with risk of neural tube defects.

Recent animal studies suggested that deregulated expression of the platelet-derived growth factor receptor alpha (PDGFRalpha) may contribute to the failure of normal neural tube closure (NTC). There is also suggestive evidence that the promoter haplotype of the PDGFRA is associated with genetic susceptibility in human neural tube defects (NTDs). The purpose of our study was to investigate the association between promoter haplotype combinations of the human PDGFRA gene and risk for NTDs in a Hispanic population from the Texas-Mexico border region. This population has a considerably higher prevalence of NTDs (16/10,000 live births) than that generally reported in the United States (8-10/10,000 live births). In the present study, NTDs were defined as spina bifida or anencephaly. The haplotype of PDGFRA gene promoter was determined by direct DNA sequence analysis. Two novel haplotypes, H2epsilon and H1beta, were found. We observed significant differences among variable haplotype groups from in vitro transient transfection studies in U2-OS osteosarcoma cell and two other cell lines (HeLa cell and MCF7 cell). Result from our case-control study demonstrated that the frequencies of haplotypes with low transcription activity were significantly higher in NTD mothers than that observed in control mothers (odds ratio=2.2, 95% CI=1.0-4.6). Infants with at least one low activity allele showed slightly higher risk (odds ratio=1.5, 95%=0.8-3.1). Our study suggests that the reduced transcriptional activity of PDGFRA gene could increase the risk of having an NTD-affected pregnancy.

Adult↗

PubMed2003

Detection of the four sequence variations of MDR1 gene using TaqMan MGB probe based real-time PCR and haplotype analysis in healthy Japanese subjects.

OBJECTIVES: P-glycoprotein (P-gp) is significant from the viewpoint of pharmacokinetics/pharmacodynamics (PK/PD). MDR1 gene encodes P-gp and has a wide variety of SNPs. As the SNPs may be one of the factors that induce pharmacogenetic individual difference, haplotype analysis is necessary to evaluate the PK/PD. DESIGN AND METHODS: The SNPs of the detected MDR1 were -129T>C, 325G>A, 2677G>T/A, and 3435C>T. For the analysis of linkage disequilibrium (LD) and haplotype analysis, and for the reconstruction of the haplotype pair, ARLEQUIN and PHASE were employed. RESULTS: The result of the chi(2) test detected significant LD between -129 and 2677, -129 and 3435, and 2677 and 3435. There were 9 haplotypes: T-G-C, T-T-C, C-T-C, T-A-C, C-A-C, T-G-T, T-T-T, C-G-T, and C-T-T. CONCLUSIONS: LD was found among the positions -129, 2677 and 3435. As a result, 9 haplotypes exists in the Japanese population. These results suggest that it would be necessary to give consideration to haplotype for the purpose of evaluating the PK/PD of the drugs transported by P-gp.

Adult↗

PubMed2001

Determination of cytokine regulatory haplotypes by induced heteroduplex analysis of DNA.

Multiple single nucleotide polymorphisms (SNP) in the promoter region of the human interleukin-10 (IL-10) gene and in the signal/leader sequence of the human transforming growth factor beta 1 (TGF-beta1) gene, have been associated with susceptibility, severity and clinical outcome for a number of diseases. One common explanation for this, is that different haplotypes of these SNPs regulate the expression of the respective cytokines. Therefore, accurate determination of haplotypes by physical linkage analysis represents an important tool in investigating the pathogenesis of such diseases. Here, we demonstrate that the use of induced heteroduplex generators (IHGs) may be used to identify haplotypes within target sequences in the IL-10 and TGF-beta1 genes. Four haplotypes were observed within the IL-10 promoter region, consisting of -1082, -851, -819 and -592 SNPs. For the TGF-beta1 signal/leader sequence, we observed three haplotypes of the T869C (Leu10Pro) and G915C (Arg25Pro) SNPs. In both cases, all combinations of these haplotypes could be resolved unequivocally with a single IHG reagent.

Base Sequence↗

PubMed2000

HLA-DR2-associated DRB1 and DRB5 alleles and haplotypes in Koreans.

There are considerable racial differences in the distribution of HLA-DR2-associated DRB1 and DRB5 alleles and the characteristics of linkage disequilibrium between these alleles. In this study, the frequencies of DR2-associated DRB1 and DRB5 alleles and related haplotypes were analyzed in 186 DR2-positive individuals out of 800 normal Koreans registered for unrelated bone marrow donors. HLA class I antigen typing was performed by the serological method and DRB1 and DRB5 genotyping by the PCR-single strand conformational polymorphism method. Only 3 alleles were detected for DR2-associated DRB1 and DRB5 genes, respectively: DRB1(*)1501 (gene frequency 8.0%), (*)1502 (3.2%), (*)1602 (0.9%); DRB5(*)0101 (8.0%), (*)0102 (3.2%), and (*)0202 (0.9%). DRB1-DRB5 haplotype analysis showed an exclusive association between these alleles: DRB1*1501-DRB5*0101 (haplotype frequency 8.0%), DRB1(*)1502-DRB5(*)0102 (3.2%), and DRB1(*)1602-DRB5(*)0202 (0.9%). The 5 most common DR2-associated A-B-DRB1 haplotypes occurring at frequencies of > or = 0.5% were A24-B52-DRB1(*)1502 (1.8%), A2-B62-DRB1(*)1501, A2-B54-DRB1(*)1501, A26-B61-DRB1(*)1501, and A24-B51-DRB1(*)1501. The remarkable homogeneity in the haplotypic associations between DR2-associated DRB1 and DRB5 alleles in Koreans would be advantageous for organ transplantation compared with other ethnic groups showing considerable heterogeneity in the distribution of DRB1-DRB5 haplotypes.

Alleles↗

PubMed2001

Class II allele and haplotype frequencies in Mexican systemic lupus erythematosus patients: the relevance of considering homologous chromosomes in determining susceptibility.

The aim of the present study was to determine the relevant major histocompatibility complex (MHC) class II alleles in the genetic susceptibility to systemic lupus erythematosus (SLE) in Mexican Mestizo patients. We examined the gene and haplotype frequencies of the HLA-DRB1, DQA1 and DQB1 alleles by polymerase chain reaction-sequence-specific oligonucleotide probes in 81 Mexican SLE Mestizo patients and 99 ethnically matched controls. We found a significantly increased frequency of the HLA-DRB1*0301 (p(c) = 0.031, odds ratio = 2.63) allele and significantly decreased frequencies of the DRB1*0802 (p(c) = 0.035) and DRB1*1101 (p(c) = 0.037) alleles in the SLE group. Haplotype analysis showed increased frequencies of DRB1*0301-DQA1*0501-DQB1*0201 (p(c) = 0.017, odds ratio = 2.97), and decreased frequency of DRB1*0802-DQA1*0401-DQB1*0402 (p(c) = 0.034) in SLE patients. The most frequently detected haplotypes in SLE patients showed different haplotypic combinations in the homologous chromosome from those found in controls. Thus, the combinations detected in SLE patients were either not detected in the control group or infrequently found. The results suggest that the DRB1*0301 is the principal class II allele associated with the genetic susceptibility to SLE in Mexican patients and that the presence of a specific haplotype of the homologous chromosome in patients with DRB1*0407-DQA1*03-DQB1*0302 and DRB1*1501-DQA1*0102-DQB1*0602 haplotypes could have an additive effect on the susceptibility to the disease. Finally, the low frequency of the DRB1*0301 and DRB1*1501 alleles in the control population suggests that the genetic admixture between Mexican Indians and Caucasian populations was an event that could have increased the risk of Mexicans to develop SLE.

Alleles↗

PubMed2001

North African genes in Iberia studied by Y-chromosome DNA haplotype V.

Haplotype V at the Y-chromosome specific DNA polymorphism (p49/TaqI) was reported in a study concerning 487 males originating from five different geographic locations in Iberia and North Africa. The highest frequency of haplotype V (68.9%) was previously observed in Berbers from Morocco, and it was previously established that this haplotype is a characteristic Berberian haplotype in North Africa. Percentages of haplotype V geographic distribution reveal a gradient of decreasing frequencies with latitude in Iberia: 40.8% in Andalusia, 36.2% in Portugal, 12.1% in Catalonia, and 11.3% in Basques; such a cline of decreasing haplotype V frequencies from the South to the North in Iberia clearly establishes a North African toward Iberian gene flow.

Adult↗

PubMed2001

Genetic relationship of the Guambino, Paez, and Ingano Amerindians of southwest Colombia using major histocompatibility complex class II haplotypes and blood groups.

We analyzed the Amerindian tribes, Guambiano, Ingano, and Paez of the southwest section of Colombia by major histocompatibility complex class II typing and blood group analysis in order to establish their genetic relationship. In addition, genetic admixture with Caucasian and African ancestry were determined based on blood group typing. The Paez showed admixture with Caucasian populations (22.4%), while the Ingano and Guambiano showed some admixture with Black populations (9.2 and 4.6%, respectively). The Ingano had MHC class II haplotypes found mainly in Amerindian and Asian populations with no evidence of class II haplotypes of African origin. MHC class II haplotypes of Amerindian and Asian populations and some haplotypes frequently found in European Caucasians and Asians and haplotypes of European Caucasians were found in Guambiano and Paez tribes. We compared our results with those previously reported for four Amerindian tribes on Northern Colombia. The presence of some MHC class II haplotypes in the Guambiano, Paez, and Ingano tribes and their absence in the Chibcha speaking groups of Northern Colombia suggest that these tribes originated, together with other Amerindians, from a separate migration or by genetic drift from an ancestral population. Therefore they are genetically distant from Chibcha speaking tribes of Colombia.

Asian People↗

PubMed2001

Extended HLA haplotypes in a Carib Amerindian population: the Yucpa of the Perija Range.

Eleven MHC loci haplotypes have been defined among a Carib speaking Amerindian population; the Yucpa, inhabiting the northern section of the Perija Range, on the limits between Colombia and Venezuela. This tribe has been known with the name of "Motilones mansos" and is located close to the Chibcha-Paeze speaking Bari or "Motilones bravos." Seventy-three full blooded Yucpa living at the villages of Aroy, Marewa, and Peraya, were selected using a genealogy previously collected by an anthropologist and tested for Bf-C4AB complement allotypes and by serology, high resolution PCR-SSO and SBT typing for HLA class 1 and class 2 alleles. Combinations of 6 HLA-A, 6 HLA-B, 5 HLA-C, 1 Bf, 3 C4AB, 3 DQA1, 3DQB1 and 2 DPA1 and 2 DPB1 alleles present in this population originate 17 different haplotypes, 3 of which represent 63% of the haplotypic constitution of the tribe. The presence of 13 individuals homozygous for 11-loci haplotypes corroborates the existence of the following allelic combinations: DRB1*0411 DQA1*03011 DQB1*0302 DPA1*01 DPB1*0402 with HLA-A*6801 C*0702 B*3909 BfS C4 32 (f = 0.3372) or with A*0204 C*0702 B*3905 (f = 0.1977) and a third haplotype which differs only in DRB1*0403 and A*2402 (f = 0.0930). The results demonstrate the isolation of the tribe and the existence of high frequencies of a reduced number of "Amerindian" ancestral and novel class 1 and class 2 alleles (B*1522, DRB1*0807) with significant linkage disequilibria. These results will be useful to test the hypothesis that differentiation of Amerindian tribal groups will have to rely on haplotypes and micropolymorphism rather than allelic lineage frequencies due to the uniformity shown thus far by the putative descendants of the original Paleo-Indians.

Colombia↗

PubMed2001

Family-based association of HLA class II alleles and haplotypes with type I diabetes in Brazilians reveals some characteristics of a highly diversified population.

The association of HLA class II haplotypes with type I diabetes was analyzed in 56 Southeastern Brazilian families using affected family-based controls (AFBAC) method. DRB1-DQA1-DQB1 alleles were determined by polymerase chain reaction/sequence-specific primer genotyping. This study first revealed the great haplotype diversity of Brazilians (65 different haplotypes even with incomplete DRB1 subtyping), probably due to the admixture of Africans genes with European and Amerindian genes in this population. The results revealed increased frequencies of the DRB1*03-DQA1*0501-DQB1*02 and DRB1*0401-DQA1*03-DQB1*0302 haplotypes in the patient group The highest risk for type I diabetes was associated with the heterozygote DRB1*03/*04 genotype as largely reported, and DRB1*03/X and DRB1*04/Y genotypes conferred a significant, but much lower disease risk. Protection from type I diabetes revealed some peculiarities in Southeastern Brazilians: a lack of significant protecting effect of the DRB1*1501-DQA1*0102-DQB1*0602 haplotype, and an apparent protection conferred by the DRB1*13-DQB1*0301, DRB1*11-DQB1*0301, and DRB1*01-DQB1*0501 two-locus haplotypes. The risk to type I diabetes in the highly diversified Southeastern Brazilians evidenced specific information to the prediction of the disease in this region of the country.

Adolescent↗

PubMed1996

The HLA-DRB9 gene and the origin of HLA-DR haplotypes.

HLA-DRB9 is a gene fragment consisting of exon 2 and flanking intron sequences. It is located at the extreme end of the DRB subregion, whose other end is demarcated by the DRB1 locus. We sequenced approximately 1400 base pairs of the segment encompassing the DRB9 locus from eight human haplotypes (DR1, DR10, DR2, DR3, DR5, DR6, DR8, and DR9, the DR4 and DR7 having been sequenced by others earlier), as well as two chimpanzee, five gorillas, one orangutan and one macaque haplotype. The analysis of these sequences indicates that the DRB9 locus, which we estimate to be more than 58 million years (my) old, has been coevolving with the DRB1 locus for the last 4.2 my. As a consequence of this coevolution, the human DRB9 alleles fall into groups that correlate with the DRB1 allelic groups and with the gene organization of the human haplotypes. This observation implies that the present-day HLA-DR haplotype groups (DR1, DR51, DR52, DR8, and DR53) were founded more than 4 my ago and have remained intact (barring minor internal rearrangements that did not recombine the DRB1 and DRB9 genes) for this period of time. The haplotypes have been transmitted during speciations from ancestral to emerging species just like allelic lineages at the DRB1 locus. Thus not only allelic but also haplotype polymorphism evolves trans-specifically.

Animals↗

PubMed1998

MHC haplotype analysis by artificial neural networks.

Conventional matching is based on numbers of alleles shared between donor and recipient. This approach, however, ignores the degree of relationship between alleles and haplotypes, and therefore the actual degree of difference. To address this problem, we have compared family members using a block matching technique which reflects differences in genomic sequences. All parents and siblings had been genotyped using conventional MHC typing so that haplotypes could be assigned and relatives could be classified as sharing 0, 1 or 2 haplotypes. We trained an Artificial Neural Network (ANN) with subjects from 6 families (85 comparisons) to distinguish between relatives. Using the outputs of the ANN, we developed a score, the Histocompatibility Index (HI), as a measure of the degree of difference. Subjects from a further 3 families (106 profile comparisons) were tested. The HI score for each comparison was plotted. We show that the HI score is trimodal allowing the definition of three populations corresponding to approximately 0, 1 or 2 haplotype sharing. The means and standard deviations of the three populations were found. As expected, comparisons between family members sharing 2 haplotypes resulted in high HI scores with one exception. More interestingly, this approach distinguishes between the 1 and 0 haplotype groups, with some informative exceptions. This distinction was considered too difficult to attempt visually. The approach provides promise in the quantification of degrees of histocompatibility.

Electrophoresis, Agar Gel↗