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In Print: Last Month's Microarray Papers of Note: Apr 10, 2012

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Last Month's Microarray Papers of Note

Journal: BMC Plant Biology. 2012 Mar 14;12(1):35.

Title: Transcriptional profile analysis of E3 ligase and hormone-related genes expressed during wheat grain development.

Authors: Capron D, et al.

A Roche NimbleGen microarray containing 39,179 UniGenes was used to study the kinetics of gene expression during wheat grain development from the early stages of cell division to the mid-grain filling stage. By comparing 11 consecutive time-points, 9,284 differentially expressed genes were identified and annotated during this study. In total, 173 E3 ligase coding genes and 126 hormone-related genes were differentially expressed during the cell division and grain filling stages, with each family displaying a different expression profile.


Journal: Diagnostic Microbiology and Infectious Disease. 2012 Mar 26. [Epub ahead of print]

Title: Evaluation of multiplex polymerase chain reaction and microarray-based assay for rapid herpesvirus diagnostics.

Authors: Mannonen L, et al.

In this study, the authors evaluated the performance of Mobidiag's multiplex PCR- and microarray-based assay, Prove-it Herpes, in a routine clinical laboratory setting for the diagnostics of 7 herpesviruses in viral central nervous system infections. Nearly 500 cerebrospinal fluid sample were analyzed for herpesvirus DNA both by existing PCR-based methods already in use at the laboratories and by the Prove-it Herpes microarray assay. The sensitivity and specificity for the microarray assay were 93 percent and 99 percent, respectively.


Journal: Genetics in Medicine. 2012 Mar 1. [Epub ahead of print]

Title: Exon-level array CGH in a large clinical cohort demonstrates increased sensitivity of diagnostic testing for Mendelian disorders.

Authors: Aradhya S, et al.

This team of researchers designed an array comparative genomic hybridization test with probes in exonic regions of 589 genes. Targeted testing was performed for 219 genes in 3,018 patients with Mendelian disorders, specifically 136 autosomal dominant, 53 autosomal recessive, and 30 X-linked disorders. Overall, 98 deletions and two duplications were identified in 53 genes, corresponding to a detection rate of 3.3 percent, and approximately 40 percent of positive findings were deletions of only one or two exons. The authors concluded that exon-level array CGH is an option for intragenic copy number analysis and should supplement sequence analysis for Mendelian disorders.


Journal: Inflammatory Bowel Diseases. 2012 Mar 29. [Epub ahead of print]

Title: Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseases.

Authors: Harris R, et al.

The authors investigated whether DNA methylation might be connected with inflammatory bowel disease in peripheral blood leukocyte DNA by using genome-wide microarrays. Two different high-throughput microarray-based methods for genome-wide DNA methylation analysis were employed. First, DNA isolated from monozygotic twin pairs concordant and discordant for IBD was interrogated by a custom-made methylation-specific amplification microarray. Second, Illumina Infinium HumanMethylation450 BeadChip arrays were used on 48 samples of DNA from discordant twin pairs and treatment-naive pediatric cases of IBD as well as controls. The microarrays were validated with bisulfite pyrosequencing. Only the Illumina chip yielded a single methylation association of IBD, leading the researchers to conclude that microarray interrogation of methylation in peripheral blood leukocyte DNA has limited ability to detect significant disease associations.


Journal: International Journal of Obesity. 2012 Mar 6. [Epub ahead of print]

Title: Ethnic differentiation of copy number variation on chromosome 16p12.3 for association with obesity phenotypes in European and Chinese populations.

Authors: Yang T, et al.

The authors set out to examine the relationship between the CNV 16p12.3 and obesity phenotypes, including body mass index and body fat mass. They noted that a variant, rs12444979, has recently been found to be in high linkage disequilibrium with CNV 16p12.3, for association with obesity in Europeans. The authors expanded on this initial research by genotyping about 4,000 subjects from European and Han Chinese populations using the Affymetrix SNP 6.0 array, and measuring BMI using dual energy X-ray absorptiometry. They confirmed the significant association between the CNV and obesity in the European population, but did not observe a significant association signal in the Chinese population. The frequencies of this deletion CNV were also different between the European and Chinese populations, according to the authors.


Journal: ISME Journal. 2012 Mar;6(3):692-702.

Title: Shifts in soil microorganisms in response to warming are consistent across a range of Antarctic environments.

Authors: Yergeau E, et al.

The authors used using pyrosequencing, qPCR, and a custom microarray called the GeoChip to monitor the response of microbial communities across disparate sub-Antarctic and Antarctic environments to 3 years of experimental field warming. They found increases in the abundance of fungi and bacteria, as well as warming effects on functional communities, specifically in the nitrogen-cycling microorganisms. They concluded that that soil microorganisms across a range of sub-Antarctic and Antarctic environments can respond to increasing temperatures.


Journal: The Lancet. 2012 Mar 31;379(9822):1214-24.

Title: The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis.

Authors: IL6R MR Consortium, et al.

This study partially relied on a custom Illumina array called the Cardiochip to show that a SNP in the IL6R gene is associated with lower risk of coronary heart disease and also altered inflammation-associated biomarkers in a way similar to an anti-inflammatory drug. The drug, called tocilizumab, is designed to inhibit the IL6R protein, an inflammatory cytokine, and is marketed by Chugai and Roche under the names Actemra and RoActemra. Co-author Brendan Keating told BioArray News last month that the study provides "evidence that IL6R is implicated in coronary heart disease" and that tocilizumab "may offer a new potential approach for preventing CHD" (BAN 3/20/2012).


Journal: Molecular Cytogenetics. 2012 Mar 13;5(1):14.

Title: Genomic SNP array as a gold standard for prenatal diagnosis of foetal ultrasound abnormalities.

Authors: Srebniak M, et al.

The authors investigated whether replacing conventional karyotyping by SNP array analysis in cases of fetal ultrasound abnormalities would increase the diagnostic yield and speed of prenatal diagnosis in clinical practice. They performed HumanCytoSNP-12 array analysis in 207 cases of fetal structural abnormalities. They found that in 24 of 207 cases, roughly 12 percent, a clinically relevant genetic abnormality was detected, but only in eight of those 24 cases would abnormalities been detected if only routine karyotyping was performed. They concluded that prenatal SNP array testing is faster than karyotyping and allows detecting smaller aberrations in addition to the microscopic unbalanced chromosome abnormalities detectable with karyotyping.


Journal: Nature. 2012 Mar 28;483(7391):570-5.

Title: Systematic identification of genomic markers of drug sensitivity in cancer cells.

Authors: Garnett M, et al.

Using 639 human cancer cell lines from a wide range of common and rare cancers, researchers did capillary sequencing of coding exons from 64 genes that are often altered in cancer. They also looked for rearrangements in several other genes, assessed microsatellite stability patterns, and used Affymetrix microarrays to generate copy number and expression data in the cell lines. The team then screened the genetically characterized cell lines for drug sensitivity or resistance, generating data on between 275 and 507 cell lines each for 130 compounds with known or suspected activity against cancer. This resulted in specific information on the genetic and molecular profiles corresponding to treatment outcomes for the drugs tested.


Journal: PLoS Genetics. 2012 Mar;8(3):e1002592.

Title: Age-dependent brain gene expression and copy number anomalies in autism suggest distinct pathological processes at young versus mature ages.

Authors: Chow M, et al.

The authors sought to identify abnormal brain gene expression patterns via whole-genome analysis of mRNA levels and copy number variations in autistic and control postmortem brain samples. They used Illumina microarrays to profile expression in prefrontal cortex tissue where excess neuron numbers and cortical overgrowth are pronounced in the majority of autism cases. They found evidence for dysregulation in pathways governing cell number, cortical patterning, and differentiation in young autistic prefrontal cortex, but the adult autistic prefrontal cortex showed dysregulation of signaling and repair pathways. The authors said the results suggest that CNVs and age-dependent gene expression changes in autism may reflect distinct pathological processes in the developing versus the mature autistic prefrontal cortex. They also hypothesize that genetic dysregulation in the developing brain leads to abnormal regional patterning, excess prefrontal neurons, cortical overgrowth, and neural dysfunction in autism.


Journal: PLoS One. 2012;7(3):e33549.

Title: Identification of a novel idiopathic epilepsy locus in Belgian Shepherd dogs.

Authors: Seppälä E, et al.

To study the clinical and genetic background of epilepsy in Belgian Shepherds, the authors conducted genome-wide association study using Affymetrix 50K SNP arrays in 40 cases and 44 controls and mapped the epilepsy locus on CFA37, which was replicated in an independent cohort. The data led researchers to a million base stretch of sequence on chromosome 37, which the researchers believe is likely to be the strongest single risk factor for epilepsy in Belgian Shepherds and could be used to develop a DNA test for breeding purposes.


Journal: PLoS One. 2012;7(3):e33968.

Title: Genotyping performance between saliva and blood-derived genomic DNAs on the DMET array: a comparison.

Authors: Hu Y, et al.

The authors' goal was to evaluate the use of saliva-derived DNA as a sample for analysis via the Affymetrix Drug Metabolism Enzymes and Transporters, or DMET, array. Following genomic DNA extraction, they determined that a large percentage of the DNA was from bacteria or fungi. A mean of 37.3 percent human amplifiable DNA was determined for saliva-derived DNAs, which resulted in a significant decrease in the genotyping call rate — 88 percent — when compared with the 99 percent call rate of blood-derived DNAs. The authors also found that the percentage of human amplifiable DNA correlated with a higher genotyping call rate, and almost all samples with more than 31.3 percent human DNA produced a genotyping call rate of at least 96 percent. They concluded that saliva-derived DNA can provide adequate genotyping quality and performs well if the sample contains greater than 31.3 percent human amplifiable DNA.


Journal: PLoS One. 2012;7(3):e34130.

Title: Design of a bovine low-density SNP array optimized for imputation.

Authors: Boichard D, et al.

This paper discusses the creation of the Illumina BovineLD BeadChip, which was designed to support imputation to higher-density genotypes in dairy and beef breeds by including SNPs that had a high minor allele frequency as well as uniform spacing across the genome. The total number of SNPs was 6,909 and accuracy of imputation to Illumina BovineSNP50 genotypes using the BovineLD chip was over 97 percent for most dairy and beef populations. Also, the authors found that the BovineLD imputations were about 3 percentage points more accurate than those from the Illumina GoldenGate Bovine3K BeadChip across multiple populations.


Journal: Proceedings of the National Academy of Sciences.

Title: Genetic dating indicates that the Asian–Papuan admixture through Eastern Indonesia corresponds to the Austronesian expansion.

Authors: Xu S, et al.

Looking to determine the genetic impact of Austronesian expansion on the languages of Southeast Asia, the authors of this study estimated recombination breakpoints in admixed genomes based on genome-wide SNP data and dated the genetic admixture between populations of Asian versus Papuan ancestry in Eastern Indonesia. Data on the Indonesian populations was generated using the Affymetrix GeneChip Human Mapping 50K Xba array. Analyses of two genome-wide datasets indicated an eastward progression of the Asian admixture signal in Eastern Indonesia beginning about 3,000 years ago. They concluded that the Austronesian expansion had a strong genetic, as well as linguistic, impact in the region.


Journal: Science. 2012 Mar 2;335(6072):1103-6.

Title: Condition-dependent transcriptome reveals high-level regulatory architecture in Bacillus subtilis.

Authors: Nicolas P, et al.

The authors report the transcriptomes of Bacillus subtilis exposed to a wide range of environmental and nutritional conditions that the organism might encounter in nature. Using tiling microarrays, the researchers mapped transcription units, or TUs, and grouped 2,935 promoters into regulons controlled by various RNA polymerase sigma factors, accounting for about a third of the observed variance in transcriptional activity. This global classification of promoters and detailed description of TUs revealed that a large proportion of the detected antisense RNAs arose from potentially spurious transcription initiation by alternative sigma factors and from imperfect control of transcription termination, according to the authors.

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