Psoriasis is associated with increased β-defensin genomic copy number

Hollox, Edward J.; Hüffmeier, Ulrike; Zeeuwen, Patrick L.J.M.; Palla, Raquel; Lascorz, Jesús; Rodijk-Olthuis, Diana; Kerkhof, P.C.M. van de; Traupe, Heiko; Jongh, Gys de; Heijer, Martin den; Reis, André; Armour, John A.L.; Schalkwijk, Joost

doi:10.1038/ng.2007.48

Cited by 597 publications

(535 citation statements)

References 15 publications

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“…41 In contrast, the increased copy number of b-defensin genes was shown to be associated with psoriasis, which is a chronic autoimmune skin disease with a prevalence of 2-3% in individuals of the European ancestry. 42,43 Apart from b-defensin genes, individuals with deletion in LCE3B and LCE3C genes of late cornified envelope (LCE) gene cluster are found to be susceptible to psoriasis. The absence of the well characterized 32 199 bp region was significantly associated (P¼1.38E À08 ) with risk of psoriasis when studied in family-based samples from Spain, The Netherlands, Italy and the United States (P¼5.4E À04 ).…”

Section: Cnv and Susceptibility To Other Common Disorders Hiv/aids Sumentioning

confidence: 99%

Implications of gene copy-number variation in health and diseases

2011

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Section: Cnv and Susceptibility To Other Common Disorders Hiv/aids Sumentioning

confidence: 99%

Implications of gene copy-number variation in health and diseases

2011

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“…These have been described as euchromatic variants (EVs) 2 (Chromosome Anomaly Collection) and involve (1) constitutional cytogenetic amplification of known CNV regions or (2) duplication, triplication or deletion of large segmentally duplicated (SD) euchromatic tracts which may include heterochromatin and accompany pseudo-dicentric variants (Table 1). Most of the EVs are clinically innocuous but the 8p23.1 EV has been associated with a number of traits [5][6][7][8] and the 4p16.1 EV co-segregated with microtia. 4 EVs need to be distinguished from pathological imbalances with which they may be similar or even identical under the light microscope.…”

Section: Introductionmentioning

confidence: 99%

Expansion of a 12-kb VNTR containing the REXO1L1 gene cluster underlies the microscopically visible euchromatic variant of 8q21.2

et al. 2013

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Copy number variants visible with the light microscope have been described as euchromatic variants (EVs) and EVs with extra G-light material at 8q21.2 have been reported only once before. We report four further patients with EVs of 8q21.2 ascertained for clinical (3) or reproductive reasons (1). Enhanced signal strength from two overlapping bacterial artificial chromosomes (BACs) and microarray analysis mapped the EV to a 284-kb interval in the reference genome. This interval consists of a sequence gap flanked by segmental duplications that contain the 12-kb components of one of the largest Variable Number Tandem Repeat arrays in the human genome. Using digital NanoString technology with a custom probe for the RNA exonuclease 1 homologue (S. cerevisiae)-like 1 (REXO1L1) gene within each 12-kb repeat, significantly enhanced diploid copy numbers of 270 and 265 were found in an EV family and a median diploid copy number of 166 copies in 216 controls. These 8q21.2 EVs are not thought to have clinical consequences as the phenotypes of the probands were inconsistent, those referred for reproductive reasons were otherwise phenotypically normal and the REXO1L1 gene has no known disease association. This EV was found in 4/3078 (1 in 770) consecutive referrals for chromosome analysis and needs to be distinguished from pathogenic imbalances of medial 8q. The REXO1L1 gene product is a marker of hepatitis C virus (HCV) infection and a possible association between REXO1L1 copy number and susceptibility to HCV infection, progression or response to treatment has not yet been excluded.

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“…[162][163][164][165][166] In addition, one study has shown the correlations of about 30 SNPs (that found to be associated with various traits by GWAS) with CNVs at r 2 40.5, this provides preliminary evidence of the associations and possible roles of CNVs in human complex traits. 161 The amount of evidence is expected to increase in the near future, when we have a better understanding of the characteristics of non-SNP variants and a more comprehensive map of them constructed upon the completion of the 1000 Genomes Project, and when more efficient and accurate methods are available to detect the non-SNP variants for disease-association studies.…”

Section: Non-snp Variants and Complex Diseasesmentioning

confidence: 81%

The pursuit of genome-wide association studies: where are we now?

et al. 2010

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It is now 5 years since the first genome-wide association studies (GWAS), published in 2005, identified a common risk allele with large effect size for age-related macular degeneration in a small sample set. Following this exciting finding, researchers have become optimistic about the prospect of the genome-wide association approach. However, most of the risk alleles identified in the subsequent GWAS for various complex diseases are common with small effect sizes (odds ratio o1.5). So far, more than 450 GWAS have been published and the associations of greater than 2000 single nucleotide polymorphisms (SNPs) or genetic loci were reported. The aim of this review paper is to give an overview of the evolving field of GWAS, discuss the progress that has been made by GWAS and some of the interesting findings, and summarize what we have learned over the past 5 years about the genetic basis of human complex diseases. This review will focus on GWAS of SNPs association for complex diseases but not studies of copy number variations.

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Psoriasis is associated with increased β-defensin genomic copy number

Cited by 597 publications

References 15 publications

Implications of gene copy-number variation in health and diseases

Implications of gene copy-number variation in health and diseases

Expansion of a 12-kb VNTR containing the REXO1L1 gene cluster underlies the microscopically visible euchromatic variant of 8q21.2

The pursuit of genome-wide association studies: where are we now?

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