Substitution patterns in alleles of immunoglobulin V genes in humans and mice

Romo‐González, Tania; Vargas-Madrazo, Enrique

doi:10.1016/j.molimm.2005.03.018

Cited by 6 publications

(9 citation statements)

References 73 publications

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“…Our analyses have facilitated the identification of novel single nucleotide polymorphisms (SNPs) within IGL and IGK gene coding regions and regulatory elements, and also revealed a novel large sequence conversion event between the IGKV proximal and distal regions. In addition, our unbiased tri-locus comparison shows a striking enrichment of structural and nucleotide diversity in the IGH locus, confirming previous suggestions that germline variation within the light chain gene loci is lower than that observed in IGH 15,22,23 .…”

Section: Introductionsupporting

confidence: 90%

Sequencing of the human IG light chain loci from a hydatidiform mole BAC library reveals locus-specific signatures of genetic diversity

Watson

Steinberg

Graves-Lindsay

et al. 2014

Preprint

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Germline variation at immunoglobulin (IG) loci is critical for pathogen-mediated immunity, but establishing complete haplotype sequences in these regions has been problematic because of complex sequence architecture and diploid source DNA. We sequenced BAC clones from the effectively haploid human hydatidiform mole cell line, CHM1htert, across the light chain IG loci, kappa (IGK) and lambda (IGL), creating single haplotype representations of these regions. The IGL haplotype generated here is 1.25 Mb of contiguous sequence, including four novel V alleles and one novel C allele and an 11.9 kb insertion. The CH17 IGK haplotype consists of two 644 kb proximal and 466 kb distal contigs separated by a large gap of unknown size; these assemblies added 49 kb of unique sequence extending into this gap. Our analysis also resulted in the characterization of seven novel IGKV alleles and a 16.7 kb region exhibiting signatures of interlocus sequence exchange between distal and proximal IGKV gene clusters. Genetic diversity in IGK/IGL was compared to that of the IG heavy chain (IGH) locus within the same haploid genome, revealing 3-fold (IGK) and 6-fold (IGL) higher diversity in the IGH locus, potentially associated with increased levels of segmental duplication and the telomeric location of IGH.

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Section: Introductionsupporting

confidence: 90%

Sequencing of the human IG light chain loci from a hydatidiform mole BAC library reveals locus-specific signatures of genetic diversity

Watson

Steinberg

Graves-Lindsay

et al. 2014

Preprint

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“…Similarly, different proteins as a whole also differ in rates of evolution. Some families such as histone proteins change sequence at a very low rate [15], whereas molecules of the immune system such as antibodies change at a 100-fold higher rate [16].…”

Section: Introductionmentioning

confidence: 99%

The evolution of protein domain families

Buljan

Bateman

2009

Biochemical Society Transactions

113

100

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Protein domains are the common currency of protein structure and function. Over 10 000 such protein families have now been collected in the Pfam database. Using these data along with animal gene phylogenies from TreeFam allowed us to investigate the gain and loss of protein domains. Most gains and losses of domains occur at protein termini. We show that the nature of changes is similar after speciation or duplication events. However, changes in domain architecture happen at a higher frequency after gene duplication. We suggest that the bias towards protein termini is largely because insertion and deletion of domains at most positions in a protein are likely to disrupt the structure of existing domains. We can also use Pfam to trace the evolution of specific families. For example, the immunoglobulin superfamily can be traced over 500 million years during its expansion into one of the largest families in the human genome. It can be shown that this protein family has its origins in basic animals such as the poriferan sponges where it is found in cell-surface-receptor proteins. We can trace how the structure and sequence of this family diverged during vertebrate evolution into constant and variable domains that are found in the antibodies of our immune system as well as in neural and muscle proteins.

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“…Previous studies of the IgV locus [33,34] and of other loci [60,61] have made it evident that polymorphism can be characterized in several ways, not only by the number of alleles and their frequency in a determined population, but also by the number of mutations per allele [60]-as well as by the distribution and type of substitutions occurring throughout the gene [61].…”

Section: Discussionmentioning

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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