Structural analysis of substitution patterns in alleles of human immunoglobulin VH genes

Romo‐González, Tania; Vargas-Madrazo, Enrique

doi:10.1016/j.molimm.2004.11.004

Cited by 7 publications

(12 citation statements)

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“…The majority of known IGHV allelic nt mutations code for aminoacid changes, and in many IGHV genes these non-synonymous sites occur disproportionately in the complementarity determining regions of the IGHV gene, 42 which are considered to be the most important for antigen recognition. [43][44][45] However, this pattern is not observed across all IGHV gene loci, suggesting that certain IGHV genes may be under different selective pressures.…”

Section: From Germline Variation To Functional Variation and Implicamentioning

confidence: 99%

“…[43][44][45] However, this pattern is not observed across all IGHV gene loci, suggesting that certain IGHV genes may be under different selective pressures. 42 Such findings imply that IGHV gene germline polymorphisms may have important functional consequences at the protein level. Indeed, functional roles for some alleles are known.…”

Section: From Germline Variation To Functional Variation and Implicamentioning

confidence: 99%

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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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Section: From Germline Variation To Functional Variation and Implicamentioning

confidence: 99%

Section: From Germline Variation To Functional Variation and Implicamentioning

confidence: 99%

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

2012

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“…Regarding this, it is important to point out that alleles have been reported for both genes in the Caucasian population. For gene V6-1, only one allele has been reported; five alleles have been found for gene V4-61 [33,46].…”

Section: Allelism Analysis Per Ighv Genementioning

confidence: 99%

“…Furthermore, it has been established that knowing and understanding the germline repertoire and its processes of evolutive diversification is fundamental because such knowledge can contribute to the understanding of the differential expression of V genes and their relationship to certain pathologies [31]. We have recently analyzed the substitution patterns in alleles of IgV genes in humans and mice [33,34] and found that in general polymorphism is considered as one of the phenomena introducing diversity in the germ line repertoire. Nevertheless, this fact only indicates how little is known about the contribution of polymorphism to the formation of repertoires of circulating antibodies, because most of the studies evaluating polymorphism concentrate on the calculation of allelic frequencies in a population.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, those studies come mostly from Caucasian populations [35][36][37][38]. By a detailed analysis of this phenomenon by means of parameters describing information of the genetic and structural properties of the substitutions, it is possible to observe patterns and evolutionary strategies for diversification acting on those genes [33,34]. In view of the above, it is important to extend the characterization of polymorphism, at least of certain genes of interest [39].…”

Section: Introductionmentioning

confidence: 99%

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Novel Substitution Polymorphisms of Human Immunoglobulin VH Genes in Mexicans

et al. 2005

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Genomic screening by 454 pyrosequencing identifies a new human IGHV gene and sixteen other new IGHV allelic variants

et al. 2011

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Complete and accurate knowledge of the genes and allelic variants of the human immunoglobulin gene loci is critical for studies of B cell repertoire development and somatic point mutation, but evidence from studies of VDJ rearrangements suggests that our knowledge of the available immunoglobulin gene repertoire is far from complete. The reported repertoire has changed little over the last 15 years. This is, in part, a consequence of the inefficiencies involved in searching for new members of large, multigenic gene families by cloning and sequencing. The advent of high-throughput sequencing provides a new avenue by which the germline repertoire can be explored. In this report, we describe pyrosequencing studies of the heavy chain IGHV1, IGHV3 and IGHV4 gene subgroups in ten Papua New Guineans. Thousands of 454 reads aligned with complete identity to 51 previously reported functional IGHV genes and allelic variants. A new gene, IGHV3-NL1*01, was identified, which differs from the nearest previously reported gene by 15 nucleotides. Sixteen new IGHV alleles were also identified, 15 of which varied from previously reported functional IGHV genes by between one and four nucleotides, while one sequence appears to be a functional variant of the pseudogene IGHV3-25. BLAST searches suggest that at least six of these new genes are carried within the relatively well-studied populations of North America, Europe or Asia. This study substantially expands the known immunoglobulin gene repertoire and demonstrates that genetic variation of immunoglobulin genes can now be efficiently explored in different human populations using high-throughput pyrosequencing.

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Structural analysis of substitution patterns in alleles of human immunoglobulin VH genes

Cited by 7 publications

References 100 publications

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

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

Novel Substitution Polymorphisms of Human Immunoglobulin VH Genes in Mexicans

Genomic screening by 454 pyrosequencing identifies a new human IGHV gene and sixteen other new IGHV allelic variants

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