5 research outputs found
Recurrent 10q22-q23 Deletions: A Genomic Disorder on 10q Associated with Cognitive and Behavioral Abnormalities
Low-copy repeats (LCRs) are genomic features that affect chromosome stability and can produce disease-associated rearrangements. We describe members of three families with deletions in 10q22.3-q23.31, a region harboring a complex set of LCRs, and demonstrate that rearrangements in this region are associated with behavioral and neurodevelopmental abnormalities, including cognitive impairment, autism, hyperactivity, and possibly psychiatric disease. Fine mapping of the deletions in members of all three families by use of a custom 10q oligonucleotide array-based comparative genomic hybridization (NimbleGen) and polymerase chain reaction–based methods demonstrated a different deletion in each family. In one proband, the deletion breakpoints are associated with DNA fragments containing noncontiguous sequences of chromosome 10, whereas, in the other two families, the breakpoints are within paralogous LCRs, removing ∼7.2 Mb and 32 genes. Our data provide evidence that the 10q22-q23 genomic region harbors one or more genes important for cognitive and behavioral development and that recurrent deletions affecting this interval define a novel genomic disorder
Quantification of Transgene-Derived Double-Stranded RNA in Plants Using the QuantiGene Nucleic Acid Detection Platform
The expanding use of RNA interference
(RNAi) in agricultural biotechnology
necessitates tools for characterizing and quantifying double-stranded
RNA (dsRNA)-containing transcripts that are expressed in transgenic
plants. We sought to detect and quantify such transcripts in transgenic
maize lines engineered to control western corn rootworm (<i>Diabrotica
virgifera virgifera</i> LeConte) via overexpression of an inverted
repeat sequence bearing a portion of the putative corn rootworm orthologue
of yeast Snf7 (DvSnf7), an essential component of insect cell receptor
sorting. A quantitative assay was developed to detect DvSnf7 sense
strand-containing dsRNA transcripts that is based on the QuantiGene
Plex 2.0 RNA assay platform from Affymetrix. The QuantiGene assay
utilizes cooperative binding of multiple oligonucleotide probes with
specificity for the target sequence resulting in exceptionally high
assay specificity. Successful implementation of this assay required
heat denaturation in the presence of the oligonucleotide probes prior
to hybridization, presumably to dissociate primary transcripts carrying
the duplex dsRNA structure. The dsRNA assay was validated using a
strategy analogous to the rigorous enzyme-linked immunosorbent assay
evaluations that are typically performed for foreign proteins expressed
in transgenic plants. Validation studies indicated that the assay
is sensitive (to 10 pg of dsRNA/g of fresh tissue), highly reproducible,
and linear over ∼2.5 logs. The assay was validated using purified
RNA from multiple maize tissue types, and studies indicate that the
assay is also quantitative in crude tissue lysates. To the best of
our knowledge, this is the first report of a non-polymerase chain
reaction-based quantitative assay for dsRNA-containing transcripts,
based on the use of the QuantiGene technology platform, and will broadly
facilitate characterization of dsRNA in biological and environmental
samples
Recurrent 10q22-q23 Deletions: A Genomic Disorder on 10q Associated with Cognitive and Behavioral Abnormalities
Quantification of Transgene-Derived Double-Stranded RNA in Plants Using the QuantiGene Nucleic Acid Detection Platform
Common sequence variants on 20q11.22 confer melanoma susceptibility
We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 times 10-15). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases