Determination of the loss of function complement C4 exon 29 CT insertion using a novel paralog-specific assay in healthy UK and Spanish populations.
Genetic variants resulting in non-expression of complement C4A and C4B genes are common in healthy European populations and have shown association with a number of diseases, most notably the autoimmune disease, systemic lupus erythematosus. The most frequent cause of a C4 "null" allele, fo...
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0022128&type=printable |
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| author | Lora Boteva IMAGEN Yee Ling Wu Josefina Cortes-Hernández Javier Martin Timothy J Vyse Michelle M A Fernando |
| author_facet | Lora Boteva IMAGEN Yee Ling Wu Josefina Cortes-Hernández Javier Martin Timothy J Vyse Michelle M A Fernando |
| author_sort | Lora Boteva |
| collection | DOAJ |
| description | Genetic variants resulting in non-expression of complement C4A and C4B genes are common in healthy European populations and have shown association with a number of diseases, most notably the autoimmune disease, systemic lupus erythematosus. The most frequent cause of a C4 "null" allele, following that of C4 gene copy number variation (CNV), is a non-sense mutation arising from a 2 bp CT insertion into codon 1232 of exon 29. Previous attempts to accurately genotype this polymorphism have not been amenable to high-throughput typing, and have been confounded by failure to account for CNV at this locus, as well as by inability to distinguish between paralogs. We have developed a novel, high-throughput, paralog-specific assay to detect the presence and copy number of this polymorphism. We have genotyped healthy cohorts from the United Kingdom (UK) and Spain. Overall, 30/719 (4.17%) individuals from the UK cohort and 8/449 (1.78%) individuals from the Spanish cohort harboured the CT insertion in a C4A gene. A single Spanish individual possessed a C4B CT insertion. There is weak correlation between the C4 CT insertion and flanking MHC polymorphism. Therefore it is important to note that, as with C4 gene CNV, disease-association due to this variant will be missed by current SNP-based genome-wide association strategies. |
| format | Article |
| id | doaj-art-b0cf4e5d017a4d9eb2c63322b9079095 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-b0cf4e5d017a4d9eb2c63322b90790952025-08-20T03:26:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2212810.1371/journal.pone.0022128Determination of the loss of function complement C4 exon 29 CT insertion using a novel paralog-specific assay in healthy UK and Spanish populations.Lora BotevaIMAGENYee Ling WuJosefina Cortes-HernándezJavier MartinTimothy J VyseMichelle M A FernandoGenetic variants resulting in non-expression of complement C4A and C4B genes are common in healthy European populations and have shown association with a number of diseases, most notably the autoimmune disease, systemic lupus erythematosus. The most frequent cause of a C4 "null" allele, following that of C4 gene copy number variation (CNV), is a non-sense mutation arising from a 2 bp CT insertion into codon 1232 of exon 29. Previous attempts to accurately genotype this polymorphism have not been amenable to high-throughput typing, and have been confounded by failure to account for CNV at this locus, as well as by inability to distinguish between paralogs. We have developed a novel, high-throughput, paralog-specific assay to detect the presence and copy number of this polymorphism. We have genotyped healthy cohorts from the United Kingdom (UK) and Spain. Overall, 30/719 (4.17%) individuals from the UK cohort and 8/449 (1.78%) individuals from the Spanish cohort harboured the CT insertion in a C4A gene. A single Spanish individual possessed a C4B CT insertion. There is weak correlation between the C4 CT insertion and flanking MHC polymorphism. Therefore it is important to note that, as with C4 gene CNV, disease-association due to this variant will be missed by current SNP-based genome-wide association strategies.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0022128&type=printable |
| spellingShingle | Lora Boteva IMAGEN Yee Ling Wu Josefina Cortes-Hernández Javier Martin Timothy J Vyse Michelle M A Fernando Determination of the loss of function complement C4 exon 29 CT insertion using a novel paralog-specific assay in healthy UK and Spanish populations. PLoS ONE |
| title | Determination of the loss of function complement C4 exon 29 CT insertion using a novel paralog-specific assay in healthy UK and Spanish populations. |
| title_full | Determination of the loss of function complement C4 exon 29 CT insertion using a novel paralog-specific assay in healthy UK and Spanish populations. |
| title_fullStr | Determination of the loss of function complement C4 exon 29 CT insertion using a novel paralog-specific assay in healthy UK and Spanish populations. |
| title_full_unstemmed | Determination of the loss of function complement C4 exon 29 CT insertion using a novel paralog-specific assay in healthy UK and Spanish populations. |
| title_short | Determination of the loss of function complement C4 exon 29 CT insertion using a novel paralog-specific assay in healthy UK and Spanish populations. |
| title_sort | determination of the loss of function complement c4 exon 29 ct insertion using a novel paralog specific assay in healthy uk and spanish populations |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0022128&type=printable |
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