scholarly journals Disequilibrium Pattern Analysis. II. Application to Danish HLA A and B Locus Data

Genetics ◽  
1987 ◽  
Vol 116 (4) ◽  
pp. 633-643
Author(s):  
William Klitz ◽  
Glenys Thomson
Keyword(s):  
Linkage Disequilibrium ◽  
Genetic Drift ◽  
Pattern Analysis ◽  
Human Leukocyte ◽  
Population Admixture ◽  
Random Genetic Drift ◽  
Leukocyte Antigen ◽  
Antigen System ◽  
Hla Haplotypes ◽  
General Method

ABSTRACT Disequilibrium pattern analysis, a general method for analyzing evolutionary events acting on pairs of tightly linked polymorphic loci, is applied to a large sample of Danish individuals typed for A and B loci of the HLA (human leukocyte antigen) system. Cases of selection on particular haplotypes are revealed from patterns of linkage disequilibrium among the HLA haplotypes. These patterns cannot be explained by either population admixture or random genetic drift. Six haplotypes out of the total array of 273 haplotypes have been identified which show in varying extents the patterns indicating selection.

Disequilibrium Pattern Analysis. I. Theory

Genetics ◽  
1987 ◽  
Vol 116 (4) ◽  
pp. 623-632
Author(s):  
Glenys Thomson ◽  
William Klitz
Keyword(s):  
Linkage Disequilibrium ◽  
Dna Sequencing ◽  
Genetic Drift ◽  
Pattern Analysis ◽  
Population Data ◽  
Distinct Pattern ◽  
Random Genetic Drift ◽  
A Value ◽  
Selection Event ◽  
Entire Array

ABSTRACT We have developed a method, disequilibrium pattern analysis, for examining the disequilibrium distribution of the entire array of two locus multiallelic haplotypes in a population. It is shown that a selected haplotype will produce a distinct pattern of linkage disequilibrium values for all generations while the selection is acting. This pattern will also presumably be maintained for many generations after the selection event, until the disequilibrium pattern is eventually broken down by genetic drift and recombination. Related haplotypes, sharing an allele with a selected haplotype, assume a value of linkage disequilibrium proportional to the frequency of the unshared allele and have a single negative value of the normalized linkage disequilibrium. The analysis assumes zero linkage disequilibrium for all allelic combinations initially. The same basic results continue to apply if the selection involves a new mutant, the occurrence of which creates linkage disequilibrium for some haplotypes. The disequilibrium pattern predicted under selection is robust with respect to the influence of migration and random genetic drift. This method is applicable to population data having linked polymorphic loci including that determined from protein or DNA sequencing.

scholarly journals Umbilical Cord Blood Units Cryopreserved in the Public Cord Blood Bank: A Breakthrough in iPSC Haplobanking?

2020 ◽  
Vol 29 ◽  
pp. 096368972092615
Author(s):  
Eun Youn Roh ◽  
Sohee Oh ◽  
Jong Hyun Yoon ◽  
Byoung Jae Kim ◽  
Eun Young Song ◽  
...  
Keyword(s):  
Cord Blood ◽  
Therapeutic Option ◽  
Human Leukocyte ◽  
Korean Population ◽  
Genomic Changes ◽  
The Public ◽  
Leukocyte Antigen ◽  
Induced Pluripotent ◽  
Efficient Option ◽  
Hla Haplotypes

The use of induced pluripotent stem cells (iPSCs) is an emerging therapeutic option for precision medicine. Cord blood (CB) cells with lower immunogenicity, fewer genomic changes, and persistent epigenetic memory might be ideal candidates for iPSC production. Based on the human leukocyte antigen (HLA) distribution of cord blood units (CBUs) in the public CB bank, we estimated the coverage of the Korean population with HLA-homozygous iPSCs to repurpose cryopreserved CBUs. We analyzed a total of 27,904 Korean CBUs donated to the public CB bank. Low-to-intermediate resolution typing was performed for HLA-A, -B, and -DRB1 alleles, and individuals possessing homozygous HLA haplotypes were identified by direct counting. Moreover, the matching probabilities for zero-mismatch transplantation were calculated for 27,904 CBUs and 50,000,000 potential Korean patients. Among the preserved CBUs, 15 HLA-A, 40 HLA-B, and 13 HLA-DRB1 alleles as well as 48 homozygous HLA-A-B-DRB1 haplotypes were identified at serological equivalents (2 digits). The 48 identified homozygous haplotypes cumulatively matched 78.18% of the 27,904 Korean CB donors as zero HLA-mismatch iPSC sources. Among the combinations of 1,699 haplotypes with frequencies greater than 0.001%, assuming a population of 50 million, those 48 haplotypes can provide a match for 78.37% of potential Korean recipients. A practicable number of HLA-A, -B, and -DRB1 homozygous iPSC lines derived from CBUs may be an efficient option in allogeneic iPSC therapy because this type of haplobanking may provide cell lines with optimal HLA matching for up to three-quarters of the Korean population.

scholarly journals The Phenotype of Celiac Disease Has Low Concordance between Siblings, Despite a Similar Distribution of HLA Haplotypes

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 479 ◽  
Author(s):  
Saana Kauma ◽  
Katri Kaukinen ◽  
Heini Huhtala ◽  
Laura Kivelä ◽  
Henna Pekki ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Environmental Factors ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Similar Distribution ◽  
Intestinal Malabsorption ◽  
Sibling Pairs ◽  
Leukocyte Antigen ◽  
Intestinal Symptoms ◽  
Hla Haplotypes

The factors determining the presentation of celiac disease are unclear. We investigated the phenotypic concordance and the distribution of human leukocyte antigen (HLA) risk haplotypes in affected siblings. One hundred sibling pairs were included. Clinical and histological parameters and HLA haplotypes were compared between the first diagnosed indexes and their siblings. The phenotype was categorized into gastrointestinal, extra-intestinal, malabsorption/anemia, and asymptomatic. The phenotype was fully concordant in 21 pairs. The most common concordant phenotype was gastrointestinal (14 pairs). Indexes had more anemia/malabsorption and extra-intestinal symptoms than siblings (45% vs. 20%, p < 0.001 and 33% vs. 12%, p < 0.001, respectively). Twenty siblings and none of the indexes were asymptomatic. The indexes were more often women (81% vs. 63%, p = 0.008). They were also more often seronegative (11% vs. 0%, p = 0.03) and younger (37 vs. 43 year, p < 0.001), and had more severe histopathology (total/subtotal atrophy 79% vs. 58%, p = 0.047) at diagnosis. The indexes and siblings were comparable in other disease features. Pairs with discordant presentation had similar HLA haplotypes more often than the concordant pairs. The phenotype was observed to vary markedly between siblings, with the indexes generally having a more severe presentation. HLA did not explain the differences, suggesting that non-HLA genes and environmental factors play significant roles.

scholarly journals Human Leukocyte Antigen (HLA) Typing Study Identifies Maternal DQ2 Susceptibility Alleles among Infertile Women: Potential Associations with Autoimmunity and Micronutrients

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3270
Author(s):  
Paola Triggianese ◽  
Carlo Perricone ◽  
Erica De Martino ◽  
Arianna D’Antonio ◽  
Maria Sole Chimenti ◽  
...  
Keyword(s):  
Risk Factors ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Leukocyte Antigen ◽  
Infertile Women ◽  
Micronutrient Status ◽  
Independent Risk Factors ◽  
Hla Haplotypes ◽  
First Time ◽  
Hla Dq2

Background. The interplay between female fertility and autoimmune diseases (AIDs) can involve HLA haplotypes and micronutrients. We analyzed the distribution of HLA-DQ2/-DQ8 in women with infertility or recurrent spontaneous abortion (RSA) and possible associations with AIDs and micronutrient status. Methods. Consecutive women (n = 187) with infertility and RSA, and controls (n = 350) were included. All women were genotyped for HLA-DQ2 (DQA1*0201, A1*05, and B1*02) and -DQ8 (DQA1*03 and DQB1*0302) alleles. Serum 25(OH)D, VB12, folate, and ferritin were evaluated. Results. DQA1*05/B1*02 and the occurrence of at least one DQ2 allele were more prevalent among RSA and infertile women than controls. Infertile women showed lower 25(OH)D and higher prevalence of AIDs than RSA women. In the multivariate analysis, DQA1*05/B1*02 was associated with a significantly higher risk of AIDs in infertile women, and DQA1*05 was independently associated with both 25(OH)D deficiency and AIDs. In RSA women, the presence of AIDs was associated with a significantly higher risk of 25(OH)D deficiency. Conclusion. Our findings showed, for the first time, a higher proportion of DQ2 alleles in infertile and RSA women as compared to controls. Predisposing DQ2 alleles are independent risk factors for AIDs and 25(OH)D deficiency in infertile women and could represent biomarkers for performing early detection of women requiring individually tailored management.

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