Sensitive and Specific Real-Time Polymerase Chain Reaction Assays to Accurately Determine Copy Number Variations (CNVs) of Human Complement C4A, C4B, C4-Long, C4-Short, and RCCX Modules: Elucidation of C4 CNVs in 50 Consanguineous Subjects with Defined HLA Genotypes

Wu, Yee Ling; Savelli, Stephanie; Yang, Yan; Zhou, Bi; Rovin, Brad H.; Birmingham, Daniel J.; Nagaraja, Haikady N.; Hebert, Lee A.; Yu, C. Yung

doi:10.4049/jimmunol.179.5.3012

Cited by 81 publications

(110 citation statements)

References 65 publications

(75 reference statements)

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…This suggests that AH18.3 might be in fact split into two distinct, although very similar, haplotypes. Of the rare RCCX variants identified in this population, A(S)-B(S) was linked to HLA alleles earlier, 25 but to dissimilar ones as described here. A trimodule with two CYP21A2 copies (the second of which contains a stop codon mutation) was found earlier in linkage with HLA-A2-B50, 28 but as no information is available about class II alleles of this specific haplotype it can only be supposed that it is identical to one of the haplotypes with duplicated CYP21A2 genes observed here.…”

Section: Characterization Of Rccx Variants Z Bánlaki Et Almentioning

confidence: 49%

“…Given the long-range LD characteristics of the region, there is presumably a strong relationship between ancestral MHC haplotypes and RCCX structural variations. Although in some cases HLA alleles were examined together with RCCX variants earlier, 25 no extensive investigation has been published yet. As even certain formerly recognized ancestral MHC haplotypes differ only in polymorphisms other than HLA alleles, 16 we analyzed five SNPs as well.…”

Section: Characterization Of Rccx Variants Z Bánlaki Et Almentioning

confidence: 99%

“…13 For detecting C4(L) and C4(S) GCNs, primer and probe sequences described elsewhere 25 were used. Amplification of both CYP21A2 and CYP21A1P genes was done using the primers 5 0 -CTCCTCCTGCAGACAAGCTG-3 0 (forward) and 5 0 -AGCTTCT TGTGGGCTTTCCA-3 0 (reverse).…”

Section: Sample Collectionmentioning

confidence: 99%

See 2 more Smart Citations

Fine-tuned characterization of RCCX copy number variants and their relationship with extended MHC haplotypes

et al. 2012

View full text Add to dashboard Cite

The human RCCX is a common multiallelic copy number variation locus whose number of segments varies between one and four in a chromosome. The monomodular form normally comprises four functional genes, but in duplicated RCCX segments generally only the gene-encoding complement component C4 produces a protein. C4 genes can code either for a C4A or a C4B isotype protein and exhibit dichotomous size variation. Distinct RCCX variants show association with numerous diseases; however, identification of the basis of these associations is often challenging, not least because the RCCX is localized in the major histocompatibility complex (MHC) region, a genomic area characterized by exceedingly long-range linkage disequilibrium. Here we present a detailed analysis on RCCX variants and their relationship with so-called 'ancestral' or 'conserved extended' MHC haplotypes in healthy Caucasians. In addition to former investigations, precise order and size of all C4A and C4B genes were determined even in trimodular RCCX structures. Considering C4 copy numbers, length, isotype specificity and CYP21A2 copy numbers, we have identified 15 distinct RCCX variants and described the RCCX structures involved in 29 repeatedly occurring MHC haplotypes. The findings should become a useful tool for future RCCX-and MHC-related disease association studies.

show abstract

Section: Characterization Of Rccx Variants Z Bánlaki Et Almentioning

confidence: 49%

Section: Characterization Of Rccx Variants Z Bánlaki Et Almentioning

confidence: 99%

See 1 more Smart Citation

Fine-tuned characterization of RCCX copy number variants and their relationship with extended MHC haplotypes

et al. 2012

View full text Add to dashboard Cite

show abstract

“…For estimating the C4 copy number, we used HeLa cell DNA as the diploid control, as described elsewhere (15). The copy number of each target was defined as 2…”

Section: Methodsmentioning

confidence: 99%

“…Genomic qPCR was performed using the Viia 7 system (Life Technologies) as described elsewhere (14). For qPCR analysis of the C4 gene (C4A and C4B), copy number status was determined by TaqMan-based genomic qPCR using 2 TaqMan assays, Hs07226349_cn and Hs07226350_cn (Life Technologies), which were specifically designed for C4A and C4B (15). For this analysis, 10 l of reaction mixture, containing 10 ng of genomic DNA, TaqMan Universal PCR Master Mix II (Life Technologies), C4A or C4B TaqMan probe, and RNaseP TaqMan probe, was used.…”

Section: Methodsmentioning

confidence: 99%

Deletion Variants of RABGAP1L, 10q21.3, and C4 Are Associated With the Risk of Systemic Lupus Erythematosus in Korean Women

Kim¹,

Jung²,

Bae³

et al. 2013

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Several copy number variations (CNVs) have been found to be associated with systemic lupus erythematosus (SLE) through the target gene approach. However, genome-wide features of CNVs and their role in the risk of SLE remain unknown. The aim of this study was to identify SLE-associated CNVs in Korean women.Methods. Genome-wide assessments of CNVs were performed in 382 SLE patients and 191 control subjects, using an Illumina HumanHap610 BeadChip genotyping platform. SLE-associated CNV regions that were identified by genome-wide association study (GWAS) were replicated in quantitative polymerase chain reaction (PCR) and deletion-typing PCR analyses in an independent sample set comprising 564 SLE patients and 511 control subjects.Results. Of 144 common CNV regions, 3 deletiontype CNV regions in 1q25.1, 8q23.3, and 10q21.3 were found to be significantly associated with SLE by GWAS analysis. In the independent replication, the CNV regions in 1q25.1 (RABGAP1L) and 10q21.3 were successfully replicated (odds ratio [OR] 1.30, P ‫؍‬ 0.038 and OR 1.90, P ‫؍‬ 3.6 ؋ 10 ؊5 , respectively), and the associations were confirmed again by deletion-typing PCR. The CNV region in the C4 gene, which showed a potential association in the discovery stage, was included in the replication analysis and was found to be significantly associated with the risk of SLE (OR 1.88, P ‫؍‬ 0.01). Through deletion-typing PCR, the exact sizes and breakpoint sequences of the deletions were defined. Individuals with the deletions in all 3 loci (RABGAP1L, 10q21.3, and C4) had a much higher risk of SLE than did those without any deletions in the 3 loci (OR 5.52, P ‫؍‬ 3.9 ؋ 10 ؊4 ). Conclusion. These CNV regions can be useful to identify the pathogenic mechanisms of SLE, and might be used to more accurately predict the risk of SLE by taking into consideration their synergistic effects on disease susceptibility.

show abstract

Analysis of human alternative first exons and copy number variation of the GJA12 gene in patients with Pelizaeus–Merzbacher‐like disease

Ruf

Uhlenberg

2008

American J of Med Genetics Pt B

View full text Add to dashboard Cite

Pelizaeus-Merzbacher-like disease (PMLD) is a heterogeneous disease with primary hypomyelination of the central nervous system. Only the minority of patients have mutations in the coding region of the GJA12 gene encoding gap junction protein alpha 12, a subunit of intercellular channels highly expressed by oligodendrocytes, the myelin forming cells of the central nervous system. No other gene has been found so far to be mutated in PMLD besides GJA12. We therefore extended the mutational screening in the GJA12 gene, searched for alternative first exons-as described in mice-determined the human 5'-end of the gene, screened therein for mutations and analyzed for copy number variations of the GJA12 gene in 14 patients with PMLD. Unlike in mice we did not find alternative first exons but detected a unique 79 bp first exon in human adolescent brain and spinal cord. No mutation in this non-coding region was found in our cohort. Copy number variation of the GJA12 gene was assessed by real-time PCR TaqMan gene expression technology, but neither patient showed an aberrant copy number. These data confirm that GJA12 alterations are a rare cause of PMLD-even after extending the screening for copy number variation and for mutations in the non-coding region of GJA12. Full genome scans in informative families and further screenings of candidate genes are feasible approaches to elucidate the genetic background of the majority of patients with PMLD.

show abstract

Sensitive and Specific Real-Time Polymerase Chain Reaction Assays to Accurately Determine Copy Number Variations (CNVs) of Human Complement C4A, C4B, C4-Long, C4-Short, and RCCX Modules: Elucidation of C4 CNVs in 50 Consanguineous Subjects with Defined HLA Genotypes

Cited by 81 publications

References 65 publications

Fine-tuned characterization of RCCX copy number variants and their relationship with extended MHC haplotypes

Fine-tuned characterization of RCCX copy number variants and their relationship with extended MHC haplotypes

Deletion Variants of RABGAP1L, 10q21.3, and C4 Are Associated With the Risk of Systemic Lupus Erythematosus in Korean Women

Analysis of human alternative first exons and copy number variation of the GJA12 gene in patients with Pelizaeus–Merzbacher‐like disease

Contact Info

Product

Resources

About