In Print: Last Month's Microarray Papers of Note
Journal: American Journal of Botany. 2012 Feb;99(2):209-18.
Title: Genomics of Compositae weeds: EST libraries, microarrays, and evidence of introgression.
Authors: Lai Z, et al.
The authors describe the development of genomic tools and resources for 11 weeds from the Compositae family that will serve as a basis for subsequent population and comparative genomic analyses. They generated 22 expressed sequence tag libraries for the 11 targeted weeds using Sanger, 454, and Illumina sequencing, compared the coverage and quality of sequence assemblies, and then developed Roche NimbleGen microarrays for expression analyses in five taxa. Introgression was detected in Centaurea and Helianthus, but not in Ambrosia or Lactuca.
Journal: American Journal of Human Genetics. 2012 Feb 10;90(2):217-28.
Title: Age-related somatic structural changes in the nuclear genome of human blood cells.
Authors: Forsberg L, et al.
Using age-stratified cohorts of 318 monozygotic twins and 296 single-born subjects, the authors used arrays to look at age-related accumulation of copy-number variation in the nuclear genomes in vivo and frequency changes for both megabase- and kilobase-range variants. According to the authors, the longitudinal analysis of individuals with structural aberrations suggests that there is a natural self-removal of aberrant cell clones from peripheral blood. The authors added that the extension of these results will allow determination of the genetic age of different somatic-cell lineages and estimation of possible individual differences between genetic and chronological age.
Journal: BJOG. 2012 Feb 7. [Epub ahead of print]
Title: Clinical utility of array comparative genomic hybridization for prenatal diagnosis: a cohort study of 3,171 pregnancies.
Authors: Lee C, et al.
The authors evaluated the clinical value of prenatal array comparative genomic hybridization in screening for submicroscopic genomic imbalances. In total, the authors screened 2,497 fetuses with 1-megabase resolution using bacterial artificial chromosome array-based CGH, and 674 fetuses with 60,000 oligonucleotide array-based CGH. They determined that prenatal array CGH is "effective" in screening for submicroscopic genomic imbalance and may add 8.2 percent to the diagnostic field, compared with conventional karyotyping, for fetuses with abnormal ultrasound results, and said that it is "particularly useful" in fetuses with karyotypic balanced translocation or marker chromosomes.
Journal: British Journal of Haematology. 2012 Feb;156(3):354-7.
Title: Integrated DNA copy number and methylation profiling of lymphoid neoplasms using a single array.
Authors: Kwee I, et al.
In this paper, the authors showed that the Illumina Infinium Methylation assay, although not originally designed for copy number profiling, is able to estimate CN changes. They compared the Illumina methylation array-generated CN profiles to those obtained with a standard technique in a series of diffuse large B-cell lymphomas and the profiles showed a "high degree of consensus," according to the authors. They concluded that the demonstration of CN profiling as an additional function of the array may impact the choice of platform for methylation profiling of hematological and solid tumors.
Journal: Clinical Genetics . 2012 Feb;81(2):128-41.
Title: Whole-genome array CGH identifies pathogenic copy number variations in fetuses with major malformations and a normal karyotype.
Authors: D'Amours G, et al.
The authors used whole-genome array comparative genomic hybridization to investigate fetuses presenting at least one major malformation detected on ultrasound, but for whom standard genetic analyses, including karyotype, failed to provide a diagnosis. They identified a clinically significant chromosomal aberration in 8.2 percent of tested fetuses, and a result of unclear clinical significance in 12.2 percent of tested fetuses.
Journal: European Journal of Human Genetics. 2012 Feb;20(2):161-5.
Title: Practical guidelines for interpreting copy number gains detected by high-resolution array in routine diagnostics.
Authors: Haanemaaijer N, et al.
The authors aimed to develop guidelines for interpreting gains detected by array analysis using array comparative genomic hybridization data of 300 patients analyzed with the 105K Agilent oligo array in a diagnostic setting. They evaluated the guidelines in a second, independent, cohort of 300 patients. They determined that a threshold of 200 kilobases is acceptable in a clinical setting, while heritability does not exclude a pathogenic nature of a gain. Evaluation of the guidelines in a second cohort of 300 patients revealed that the interpretation guidelines were "clear, easy to follow and efficient."
Journal: Human Molecular Genetics . 2012 Feb 15;21(4):947-57.
Title: A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13.
Authors: Cho M, et al.
The authors performed a genome-wide association study using a total of 3,499 chronic obstructive pulmonary disease cases and 1,922 control subjects from four cohorts. Genotyping was performed on the Illumina array platform with additional markers imputed using 1000 Genomes Project data and results were summarized using fixed-effect meta-analysis. The authors identified a new genome-wide significant locus on chromosome 19q13. This region includes genes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior.
Journal: Journal of Dairy Science. 2012 Feb;95(2):909-17.
Title: Genomic prediction for Nordic Red cattle using one-step and selection index blending.
Authors: Su G, et al.
This study investigated the accuracy of direct genomic breeding values using a genomic best linear unbiased prediction model; genomic enhanced breeding values, or GEBV, using a one-step blending approach; and GEBV using a selection index blending approach for 15 traits of Nordic Red cattle. The data comprised 6,631 bulls of which 4,408 bulls were genotyped using the Illumina Bovine SNP50 BeadChip. Based on the validation analyses, averaged over the 15 traits, the reliability of direct genomic breeding values for bulls without daughter records was 11 percent higher than the reliability of conventional pedigree index. Further gain of 0.9 percentage points was achieved by combining information from conventional pedigree index using the selection index blending, and gain of 1.3 percentage points was achieved by combining information of genotyped and nongenotyped bulls simultaneously applying the one-step blending. The authors concluded that genomic selection can "greatly improve" the accuracy of preselection for young bulls in the Nordic Red population, and the one-step blending approach is a good alternative to predict GEBV in practical genetic evaluation programs.
Journal: Molecular and Cellular Probes. 2012 Feb;26(1):6-10
Title: Economic high-throughput-identification of influenza A subtypes from clinical specimens with a DNA-oligonucleotide microarray in an outbreak situation.
Authors: Bandt D, et al.
The assay is based on the hybridization of labeled amplicons from hemagglutinin and neuraminidase reverse transcriptase-PCRs using consensus primer pairs to subtype-specific probes on microtiterstripe-mounted DNA microarrays. An algorithm for semi-automatic data interpretation of raw data and assignment to H and N subtypes was used. Altogether, 191 samples were genotyped. At least 130 out of 147 array-positive samples were unambiguously assignable and 82 samples from the swine flu outbreak were correctly identified.
Journal: Molecular Cytogenetics. 2012 Feb 2;5:10.
Title: CGH and SNP array using DNA extracted from fixed cytogenetic preparations and long-term refrigerated bone marrow specimens.
Authors: Mackinnon R, et al.
The authors assessed DNA extracted from fixed cytogenetic preparations and bone marrow specimens taken during the assessment of hematological malignancies using both SNP arrays and array comparative genomic hybridization. They found that both SNP array and array CGH can be performed on genomic DNA extracted from cytogenetic specimens stored in Carnoy's fixative, and from bone marrow which has been stored unfrozen, at 4 degrees Celsius for at least 36 days. They also describe a procedure for extracting a usable concentration of total genomic DNA from cytogenetic suspensions of low cellularity.
Journal: Molecular Oncology. 2012 Feb;6(1):98-107.
Title: Genomic imbalances in endometrial adenocarcinomas — comparison of DNA ploidy, karyotyping and comparative genomic hybridization.
Authors: Kildal W, et al.
The authors compared DNA ploidy status with karyotypic and comparative genomic hybridization data on 51 endometrial adenocarcinomas. The authors observed a correlation between increasing DNA ploidy complexity and increasing number of copy alterations. They found that gains of material from chromosomes 8 and 7 might be specifically correlated to DNA aneuploidy in endometrial adenocarcinomas since 63 percent and 50 percent of the aneuploid compared to 3 percent of the diploid tumors showed imbalances involving these chromosomes.
Journal: Nature. 2012 Feb 15. [Epub ahead of print]
Title: IDH mutation impairs histone demethylation and results in a block to cell differentiation.
Authors: Lu C, et al.
In an effort to understand the epigenetic consequences of IDH1 mutation, the authors used Illumina's Infinium HumanMethylation450 array to look at genome-wide methylation patterns in astrocyte cells with or without a glioma-associated substitution in IDH1. In astrocytes that had been passaged as many as 50 times, researchers found distinct genome-wide methylation patterns depending on whether cells had wild type or mutant IDH1. In particular, they saw a jump in methylation at nearly 31,000 CpG sites in astrocytes containing the IDH1 mutation. Additionally, when they focused on a set of low-grade glioma samples, researchers saw that almost all of the tumors with hypermethylation, G-CIMP related phenotypes, and G-CIMP transcriptional profiles also contained glitches in either IDH1 or IDH2.
Journal: Nature. 2012 Feb 15;482(7386):519-23.
Title: The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila.
Authors: Liu N, et al.
The authors used Drosophila arrays to profile microRNAs and track gene expression in brain samples from young, middle-aged, and old fruit flies, looking for patterns that correspond to age and neurodegeneration-related processes. The hunt led them to miR-34, a miRNA that's switched on in adult flies and shows enhanced expression with age. In the absence of this miRNA, investigators saw signs of accelerated aging and neurodegeneration, whereas higher miR-34 levels appeared to extend fruit fly lifespan and curb age-associated declines in brain structure — patterns that appear to reflect miR-34's role in keeping developmental genes silent in adulthood.
Journal: Nature Genetics . 2012 Feb 5;44(3):328-333.
Title: Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke.
Authors: The International Stroke Genetics Consortium, et al.
To look for new stroke risk factors and their relationship to specific stroke subtypes, researchers used Illumina arrays to genotype 3,548 individuals from the UK and Germany who had experienced one of the ischemic stroke subtypes. They compared their genetic patterns with those found in samples from 5,972 unaffected controls from the same populations. After narrowing in on the most suspicious sites in the genome in this discovery group, the team attempted to verify 45 candidate loci — including seven loci implicated previously in stroke and 38 suspicious new sites — through a two-stage replication study involving another 5,859 stroke-affected individuals and 6,281 controls from Europe and the US. The search produced four loci: two known cardioembolic stroke-associated loci near the PITX2 and ZFHX3 genes, a locus on chromosome 9 that was previously found to affect large vessel stroke risk, and a new large vessel stroke risk locus on chromosome 7. The team further verified the association between large vessel stroke and the chromosome 7 SNP, which falls in an intron of HDAC9, by testing another 735 stroke cases and almost 28,600 controls.
Journal: Oncotarget.2012 Feb;3(2):212-23.
Title: A gene expression profile test for the differential diagnosis of ovarian versus endometrial cancers.
Authors: Lal A, et al.
This paper discussed the Pathwork Tissue of Origin Endometrial Test, which distinguishes primary epithelial ovarian and endometrial cancers in formalin-fixed, paraffin-embedded specimens using a 316-gene classification model. The test was validated in a blinded study using a pre-specified algorithm and microarray files for 75 metastatic, poorly differentiated or undifferentiated specimens with a known ovarian or endometrial cancer diagnosis. Measures of test performance included a 94.7 percent overall agreement with the known diagnosis.
Journal: PLoS Biology.2012 Feb;10(2):e1001258.
Title: Genome-wide analysis of the world's sheep breeds reveals high levels of historic mixture and strong recent selection.
Authors: Kijas J, et al.
Using Illumina OvineSNP50 BeadChips, the International Sheep Genomics Consortium genotyped nearly 3,000 sheep from 74 different breeds, producing a map of genetic diversity in sheep, tracing both the breeding history of the livestock species and identifying regions in the genome that have changed in response to selection for genes controlling desired traits such as coat color, body size, reproductive qualities, and the presence or lack of horns. The authors believe the results will inform the adoption of genomic selection by industry, and will provide more insight for others in the research community.
BioArray News spoke with lead author James Kijas about the study last month (BAN 2/28/2012)
Journal: PLoS Genetics. 2012 Feb;8(2):e1002532.
Title: Genome-wide association study in East Asians identifies novel susceptibility loci for breast cancer.
Authors: Long J, et al.
The authors conducted a four-stage genome-wide association study in 19,091 cases and 20,606 controls of East Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, they evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects. SNP rs9485372, near the TGF-β activated kinase gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, as did SNP rs7107217, located at 11q24.3.
Journal: PLoS One. 2012;7(2):e31745.
Title: Genome-wide SNP detection, validation, and development of an 8K SNP array for apple.
Authors: Chagne D, et al.
The International RosBreed SNP Consortium worked with Illumina to develop a SNP screening tool for genome-wide evaluation of allelic variation in apple breeding germplasm. For genome-wide SNP discovery, 27 apple cultivars were chosen to represent worldwide breeding germplasm and resequenced at low coverage with the Illumina Genome Analyzer II. A total of 2,113,120 SNPs were detected, corresponding to one SNP to every 288 basepairs of the genome. Of that, a total of 7,867 apple SNPs were selected for the IRSC's apple 8K SNP array, of which 5,554 were polymorphic after evaluation in segregating families and a germplasm collection. The authors claim the tool will enable marker-locus-trait association discovery, description of the genetic architecture of quantitative traits, investigation of genetic variation, and genomic selection in apple.
Journal: Schizophrenia Bulletin. 2012 Feb 8. [Epub ahead of print]
Title: Rare CNVs and tag SNPs at 15q11.2 are associated with schizophrenia in the Han Chinese population.
Authors: Zhao Q, et al.
The authors investigated the role of both rare copy number variants and common SNPs at 15q11.2 in schizophrenia in the Chinese Han population by screening deletions at 15q11.2 in 2,058 schizophrenia patients and 3,275 normal controls using Affymetrix 500K and 6.0 SNP arrays. They found a triple increase of deletions in cases over controls. The most significant SNP in schizophrenia was rs4778334. They also found that SNP rs1009153 in CYFIP1 was associated with schizophrenia. This led them to conclude that both rare deletions and common variants at 15q11.2 are associated with schizophrenia in the Chinese Han population.
Journal: The New Phytologist. 2012 Feb 6. [Epub ahead of print]
Title: Genomic selection for growth and wood quality in eucalyptus: capturing the missing heritability and accelerating breeding for complex traits in forest trees.
Authors: Resende M, et al.
The authors assessed the effectiveness of genomic selection in two unrelated eucalyptus breeding populations with contrasting effective population sizes genotyped with 3,000 diverse array technology markers. Prediction models were developed for tree circumference and height growth, wood specific gravity, and pulp yield using a random regression best linear unbiased predictor. Genomic regions explaining trait variation largely coincided between populations, although models predicted poorly across populations, likely as a result of variable patterns of linkage disequilibrium, inconsistent allelic effects, and genotype-environment interaction. The authors concluded that while genomic selection brings a new perspective to understanding quantitative trait variation in forest trees and provides a means for applied tree improvement, population-specific predictive models will likely drive the initial applications of genomic selection in forest tree breeding.