Ultraconserved regions in multiple sclerosis

Ban, Masashi; Maranian, Mel; Yeo, Tai Wai; Gray, Julia; Compston, Alastair; Sawcer, Stephen

doi:10.1038/sj.ejhg.5201457

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…The majority of tested UCEs are expressed in the central and peripheral nervous systems ( Bejerano et al 2006 ; Pennacchio et al 2006 ). A few preliminary attempts to link mutations in UCEs to human neural disorders, including multiple sclerosis, mental retardation, and autism have been unsuccessful, thus raising the question of the importance of these elements in the proper expression and function of their surrounding genes ( Ban et al 2005 ; Richler et al 2006 ; Bottani et al 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Widespread Ultraconservation Divergence in Primates

Ovcharenko

2008

Molecular Biology and Evolution

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The distribution and evolution of ultraconserved elements (UCEs, DNA stretches that are perfectly identical in primates and rodents) were examined in genomes of 3 primate species (human, chimpanzee, and rhesus macaque). It was found that the number of UCEs has decreased throughout primate evolution. At least 26% of ancestral UCEs have diverged in hominoids, whereas an additional 17% have accumulated one or more single nucleotide polymorphisms in the human genome. Sequence polymorphism analyses indicate that mutation fixation within an UCE can trigger a relaxation in the selective constraint on that element. Homogeneous mutation accumulations in UCEs served as a template by which purifying selection acted more effectively on protein-coding UCEs. Gene ontology annotation suggests that UCE sequence variation, primarily occurring in noncoding regions, might be linked to the reprogramming of the expression pattern of transcription factors and developmentally important genes. Many of these genes are expressed in the central nervous system. Finally, UCE sequence variability within human populations has been identified, including population-specific nonsynonymous changes in protein-coding regions.

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Section: Introductionmentioning

confidence: 99%

Widespread Ultraconservation Divergence in Primates

Ovcharenko

2008

Molecular Biology and Evolution

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“…The minor allele frequency (MAF) in German control population is 0.39, whereas the MAF is 0.34 in the Italian control population (P 5 0.00007). Remarkably, Ban et al (2) analyzed this SNP in 938 British trio families (an affected individual and both parents) for an influence on multiple sclerosis risk. Here, the MAF was 0.39 matching the allele frequency from our German study population.…”

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confidence: 99%

Reply: SNPs in ultraconserved elements and familial breast cancer risk

Yang

Burwinkel

2009

Carcinogenesis

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Dear Sir, We thank I. Catucci et al. (in preparation) for performing a replication study on the two ultraconserved element (UCE) variants rs2056116 and rs9572903 by analyzing an Italian study population of familial breast cancer cases. Beforehand, we had analyzed different single-nucleotide polymorphism (SNPs) in UCEs and found the variant rs2056116 to be associated with familial breast cancer risk especially in the (premenopausal) early age group investigating a German study population (1). Catucci et al., however, did not find any association of this variant with familial breast cancer although the inclusion criteria for the familial BRCA1/2 mutation-negative breast cancer cases were quite similar to ours.Interestingly, the allele frequencies of this variant were significantly different in the investigated German and Italian study populations. The minor allele frequency (MAF) in German control population is 0.39, whereas the MAF is 0.34 in the Italian control population (P 5 0.00007). Remarkably, Ban et al. (2) analyzed this SNP in 938 British trio families (an affected individual and both parents) for an influence on multiple sclerosis risk. Here, the MAF was 0.39 matching the allele frequency from our German study population. Thus, the allele frequency of the investigated Italian study population is significantly different from the so far investigated German and British study populations.This might be a hint that population-specific factors and/or a different linkage situation with a causative SNP may explain the discrepancy between the two studies. However, as Catucci et al. discussed, also statistical fluctuations might be a quite likely explanation for these observations.Finally, we completely agree with Catucci et al. that large multiplecenter studies are necessary to estimate the effect of this variant on breast cancer risk and clarify possible population specific factors. Hum. Genet., 13, 998-999.

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Non-coding RNAs: Identification of Cancer-Associated microRNAs by Gene Profiling

Ferdin

Kunej

Calin

2010

Technol Cancer Res Treat

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MicroRNAs (miRNAs) belong to the heterogeneous class of non-coding RNAs (ncRNAs), which are by definition RNA molecules that do not encode for proteins, but have instead important structural, catalytic or regulatory functions. In this review we first provide an overview of the different ncRNA families, focusing in particular on miRNAs and their relevance in tumour development and progression. Second we shortly describe the available ncRNA expression profiling methods, which comprise microarray, bead-based hybridization methods, in situ hybridization, quantitative real-time polymerase chain reaction, cloning and deep sequencing methods. Finally, we used the PubMed database to perform an extensive literature search for miRNA expression profiling research articles in cancer and identified 58 studies that were published between 2004 and 2009; we identified 70 miRNAs that were reported in at least five studies as being either up- or downregulated, depending on the type of cancer, and 192 miRNAs that were reported to be up- or downregulated in at least two reports. MiRNA expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis, and response to treatment. Based on the most important findings we discuss the possible use of miRNAs as clinical biomarkers in the management of cancer patients for diagnosis, prognosis, and response to therapy.

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Ultraconserved regions in multiple sclerosis

Abstract: aThe proportion of potential genotypes successfully recorded. b After Bonferroni correction none of these results are statistically significant.

Cited by 3 publications

References 6 publications

Widespread Ultraconservation Divergence in Primates

Widespread Ultraconservation Divergence in Primates

Reply: SNPs in ultraconserved elements and familial breast cancer risk

Non-coding RNAs: Identification of Cancer-Associated microRNAs by Gene Profiling

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