Ethnic Differences in V<sub>H</sub> Gene Polymorphism

Sasso, Eric H.; Buckner, Jane H.; Suzuki, Lucy A.

doi:10.1111/j.1749-6632.1995.tb55808.x

Cited by 7 publications

(5 citation statements)

References 4 publications

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“…The majority of the African individuals bear IGHV1-69 gene duplication while in the Asian groups gene duplication hardly occurs. Indeed, nearly every CNV studied in IGHV to date has been shown to exhibit population-specific patterns 3 26 27 . This remarkable population-specific diversity is also demonstrated with the frequencies of the F/L genotypes.…”

Section: Discussionmentioning

confidence: 99%

IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity

Avnir

Watson

Glanville

et al. 2016

Sci Rep

170

182

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IGHV polymorphism provides a rich source of humoral immune system diversity. One important example is the IGHV1-69 germline gene where the biased use of alleles that encode the critical CDR-H2 Phe54 (F-alleles) to make broadly neutralizing antibodies (HV1-69-sBnAb) to the influenza A hemagglutinin stem domain has been clearly established. However, whether IGHV1-69 polymorphism can also modulate B cell function and Ab repertoire expression through promoter and copy number (CN) variations has not been reported, nor has whether IGHV1-69 allelic distribution is impacted by ethnicity. Here we studied a cohort of NIH H5N1 vaccinees and demonstrate for the first time the influence of IGHV1-69 polymorphism on V-segment usage, somatic hypermutation and B cell expansion that elucidates the dominance of F-alleles in HV1-69-sBnAbs. We provide evidence that Phe54/Leu54 (F/L) polymorphism correlates with shifted repertoire usage of other IGHV germline genes. In addition, we analyzed ethnically diverse individuals within the 1000 genomes project and discovered marked variations in F- and L- genotypes and CN among the various ethnic groups that may impact HV1-69-sBnAb responses. These results have immediate implications for understanding HV1-69-sBnAb responses at the individual and population level and for the design and implementation of “universal” influenza vaccine.

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Section: Discussionmentioning

confidence: 99%

IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity

Avnir

Watson

Glanville

et al. 2016

Sci Rep

170

182

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“…This is in sharp contrast to observations from studies of the IGHV locus. Early restriction fragment length polymorphism (RFLP)-based analyses pointed to duplications of sequences that came to be known as IGHV3-23 and IGHV1-69 [66][67][68][69][70]. More recently, the duplication of these two genes and of three other functional genes was confirmed, first by analysis of AIRR-Seq data [71] and then from genomic assembly data, including the second complete assembly of the IGHV locus [14].…”

Section: Discussionmentioning

confidence: 99%

T cell receptor beta germline variability is revealed by inference from repertoire data

et al. 2022

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Background T and B cell receptor (TCR, BCR) repertoires constitute the foundation of adaptive immunity. Adaptive immune receptor repertoire sequencing (AIRR-seq) is a common approach to study immune system dynamics. Understanding the genetic factors influencing the composition and dynamics of these repertoires is of major scientific and clinical importance. The chromosomal loci encoding for the variable regions of TCRs and BCRs are challenging to decipher due to repetitive elements and undocumented structural variants. Methods To confront this challenge, AIRR-seq-based methods have recently been developed for B cells, enabling genotype and haplotype inference and discovery of undocumented alleles. However, this approach relies on complete coverage of the receptors’ variable regions, whereas most T cell studies sequence a small fraction of that region. Here, we adapted a B cell pipeline for undocumented alleles, genotype, and haplotype inference for full and partial AIRR-seq TCR data sets. The pipeline also deals with gene assignment ambiguities, which is especially important in the analysis of data sets of partial sequences. Results From the full and partial AIRR-seq TCR data sets, we identified 39 undocumented polymorphisms in T cell receptor Beta V (TRBV) and 31 undocumented 5 ′ UTR sequences. A subset of these inferences was also observed using independent genomic approaches. We found that a single nucleotide polymorphism differentiating between the two documented T cell receptor Beta D2 (TRBD2) alleles is strongly associated with dramatic changes in the expressed repertoire. Conclusions We reveal a rich picture of germline variability and demonstrate how a single nucleotide polymorphism dramatically affects the composition of the whole repertoire. Our findings provide a basis for annotation of TCR repertoires for future basic and clinical studies.

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“…5 Interestingly, the frequency of allele IGHV3-23*03 has also been shown to vary considerably across populations, occurring in 21% of Asians, but only 9% in African Americans and 1.4% in Caucasians. 29 In addition, Sasso et al…”

Section: From Germline Variation To Functional Variation and Implicamentioning

confidence: 99%

“…These were the first CNV described in the IGH locus [19][20][21][22][23][24] (locations of these polymorphisms are depicted in the IMGT IGH locus representation 10 ). The presence of alternate IGHV haplotypes in the IGHV cluster has been explored extensively using a variety of techniques, including restriction-fragment length polymorphisms, [25][26][27][28][29][30] analysis of largeinsert clones, [31][32][33][34][35] and PCR and microarray-based methods utilizing haploid sperm samples. [36][37][38][39] These approaches have identified a number of CNV polymorphisms, including insertions Figure 1.…”

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confidence: 99%

The immunoglobulin heavy chain locus: genetic variation, missing data, and implications for human disease

2012

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The immunoglobulin (IG) loci consist of repeated and highly homologous sets of genes of different types, variable (V), diversity (D) and junction (J), that rearrange in developing B cells to produce an individual's highly variable repertoire of expressed antibodies, designed to bind to a vast array of pathogens. This repeated structure makes these loci susceptible to a high frequency of insertion and deletion events through evolutionary time, and also makes them difficult to characterize at the genomic level or assay with high-throughput techniques. Given the central role of antibodies in the adaptive immune system, it is not surprising that early candidate gene approaches showed that germline polymorphisms in these regions correlated with susceptibility to both infectious and autoimmune diseases. However, more recent studies, particularly those using high-throughput genome-wide arrays, have failed to implicate these loci in disease. In this review of the IG heavy chain variable gene cluster (IGHV), we examine how poorly we understand the distribution of haplotype variation in this genomic region, and we argue that this lack of information may mask candidate loci in the IGHV gene cluster as causative factors for infectious and autoimmune diseases.

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Ethnic Differences in V_H Gene Polymorphism

Cited by 7 publications

References 4 publications

IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity

IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity

T cell receptor beta germline variability is revealed by inference from repertoire data

The immunoglobulin heavy chain locus: genetic variation, missing data, and implications for human disease

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Ethnic Differences in VH Gene Polymorphism

Cited by 7 publications

References 4 publications

IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity

IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity

T cell receptor beta germline variability is revealed by inference from repertoire data

The immunoglobulin heavy chain locus: genetic variation, missing data, and implications for human disease

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Ethnic Differences in V_H Gene Polymorphism