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PubMed2004

Plasticity of gene expression in injured human dorsal root ganglia revealed by GeneChip oligonucleotide microarrays.

Root avulsion from the spinal cord occurs in brachial plexus lesions. It is the practice to repair such injuries by transferring an intact neighbouring nerve to the distal stump of the damaged nerve; avulsed dorsal root ganglia (DRG) are removed to enable nerve transfer. Such avulsed adult human cervical DRG ( [Formula: see text] ) obtained at surgery were compared to controls, for the first time, using GeneChip oligonucleotide arrays. We report 91 genes whose expression levels are clearly altered by the injury. This first study provides a global assessment of the molecular events or "gene switches" as a consequence of DRG injuries, as the tissues represent a wide range of surgical delay, from 1 to 100 days. A number of these genes are novel with respect to sensory ganglia, while others are known to be involved in neurotransmission, trophism, cytokine functions, signal transduction, myelination, transcription regulation, and apoptosis. Cluster analysis showed that genes involved in the same functional groups are largely positioned close to each other. This study represents an important step in identifying new genes and molecular mechanisms in human DRG, with potential therapeutic relevance for nerve repair and relief of chronic neuropathic pain.

Adult↗
PubMed2005

Low density DNA microarray for detection of most frequent TP53 missense point mutations.

BACKGROUND: We have developed an oligonucleotide microarray (genosensor) utilizing a double tandem hybridization technique to search for 9 point mutations located in the most frequently altered codons of the TP53 gene. Isolated and multiplexed PCR products, 108 and 92 bp long, from exons 7 and 8, respectively, were obtained from 24 different samples. Single-stranded target DNA was then prepared from isolated or multiplexed PCR products, through cyclic DNA synthesis. Independent ssDNA's were annealed with the corresponding pairs of labeled stacking oligonucleotides to create partially duplex DNA having a 7-nt gap, which contains the sequence that will be interrogated by the capture probes forming double tandem hybridization. In the case of multiplexed ssPCR products, only two stacking oligonucleotides were added per target, therefore the gap for the PCR products having two consecutive codons to be interrogated in exon 7 was 12 nt long, so only single tandem hybridization was produced with these respective probes. RESULTS: 18 codon substitutions were found by DNA sequencing. In 13 of them a perfect correlation with the pattern of hybridization was seen (In 5 no signal was seen with the wt probe while a new signal was seen with the appropriate mutant probe, and in 8 more, as expected, no signal was seen with any probe due to the absence of the corresponding probe in the array). In 3 other cases a mutation was falsely suggested by the combination of the absence of the wild type signal along with a false signal in the other probe. In the other 2 cases the presence of the mutation was not detected due to the production of a false hybridization signal with the wild type probe. In both cases (false mutation or no mutation detected) relatively stable mismatched target/probe duplexes should be formed. These problems could be avoided by the addition of probes to improve the performance of the array. CONCLUSION: Our results demonstrate that a simple TP53 microarray employing short (7-mer) probes, used in combination with single or double tandem hybridization approach and a simple or multiplex target preparation method, can identify common TP53 missense mutations from a variety of DNA sources with good specificity.

Base Sequence↗
PubMed2002

Development and production of an oligonucleotide MuscleChip: use for validation of ambiguous ESTs.

BACKGROUND: We describe the development, validation, and use of a highly redundant 120,000 oligonucleotide microarray (MuscleChip) containing 4,601 probe sets representing 1,150 known genes expressed in muscle and 2,075 EST clusters from a non-normalized subtracted muscle EST sequencing project (28,074 EST sequences). This set included 369 novel EST clusters showing no match to previously characterized proteins in any database. Each probe set was designed to contain 20-32 25 mer oligonucleotides (10-16 paired perfect match and mismatch probe pairs per gene), with each probe evaluated for hybridization kinetics (Tm) and similarity to other sequences. The 120,000 oligonucleotides were synthesized by photolithography and light-activated chemistry on each microarray. RESULTS: Hybridization of human muscle cRNAs to this MuscleChip (33 samples) showed a correlation of 0.6 between the number of ESTs sequenced in each cluster and hybridization intensity. Out of 369 novel EST clusters not showing any similarity to previously characterized proteins, we focused on 250 EST clusters that were represented by robust probe sets on the MuscleChip fulfilling all stringent rules. 102 (41%) were found to be consistently "present" by analysis of hybridization to human muscle RNA, of which 40 ESTs (39%) could be genome anchored to potential transcription units in the human genome sequence. 19 ESTs of the 40 ESTs were furthermore computer-predicted as exons by one or more than three gene identification algorithms. CONCLUSION: Our analysis found 40 transcriptionally validated, genome-anchored novel EST clusters to be expressed in human muscle. As most of these ESTs were low copy clusters (duplex and triplex) in the original 28,000 EST project, the identification of these as significantly expressed is a robust validation of the transcript units that permits subsequent focus on the novel proteins encoded by these genes.

Algorithms↗
PubMed2003

Differential regulation of TGF-beta signaling through Smad2, Smad3 and Smad4.

Smad transcription factors mediate the growth inhibitory effect of transforming growth factor-beta (TGF-beta) in many cell types. Mutational inactivation of Smads has been correlated with loss of responsiveness to TGF-beta-mediated signal transduction. In this study, we compare the contribution of individual Smads to TGF-beta-induced growth inhibition and endogenous gene expression in isogenic cellular backgrounds. Smad2, Smad3 and Smad4 expression were selectively inhibited in differentiation-competent cells by using improved antisense molecules. We found that TGF-beta mediates its inhibitory effect on HaCaT keratinocyte cell growth predominantly through Smad3. Inhibition of Smad3 expression was sufficient to interfere with TGF-beta-induced cell cycle arrest and to induce or suppress endogenous cell cycle regulators. Inhibition of Smad4 expression exhibited a partial effect, whereas inhibition of Smad2 expression had no effect. By gene expression profiling, we identified TGF-beta-dependent genes that are differentially regulated by Smad2 and Smad3 under regular growth conditions on a genome-wide scale. We show that Smad2, Smad3 and Smad4 contribute to the regulation of TGF-beta responses to varying extents, and demonstrate, in addition, that these Smads exhibit distinct roles in different cell types.

Blotting, Western↗
PubMed2006

Transcriptome analysis of FSH and FSH variant stimulation in granulosa cells from IVM patients reveals novel regulated genes.

FSH is crucial for oocyte maturation and fertility and is the main component in infertility treatment in assisted reproduction. The granulosa cells expressing the FSH receptor interact with the oocyte and provide nourishing substrates controlling the oocyte maturation. Thus, transcriptome analysis of granulosa cells stimulated by FSH is of major importance in understanding the communication between oocytes and granulosa cells. In this study, gene expression profiles were assessed in human granulosa cells from normal cycling in vitro maturation (IVM) patients using oligonucleotide gene chips. Granulosa cells were stimulated for 2 h with either FSH or a previously generated glycosylated FSH variant (FSH1208) that exhibited increased in vivo activity because of prolonged half-life. The analysis identified 74 significantly FSH/FSH1208 regulated genes. Amongst these were well known FSH regulated genes as well as genes not previously described to be important in the FSH signalling pathway. These novel FSH regulated genes include transcription factors [cAMP responsive element modulator (CREM)/inducible cAMP early repressors (ICER), GATA 6, ZFN 361, Bcl11a, CITED1 and TCF 8] and other regulatory proteins and enzymes (IGF-BP3, syntaxin and PCK1) possibly important for oocyte/granulosa cell interaction and function. Array data were validated for 13 genes by northern blots or RT-PCR. Furthermore, no significant differences in gene regulation were detected between the two FSH analogs. This work uncovers novel data important for understanding the folliculogenesis. Furthermore, the results suggest that FSH1208 has a gene expression profile like FSH and thus, in the light of known prolonged in vivo activity, might be a candidate for improved infertility treatment.

Adolescent↗
PubMed2006

Identical probes on different high-density oligonucleotide microarrays can produce different measurements of gene expression.

BACKGROUND: There are many potential sources of variability in a microarray experiment. Variation can arise from many aspects of the collection and processing of samples for gene expression analysis. Oligonucleotide-based arrays are thought to minimize one source of variability as identical oligonucleotides are expected to recognize the same transcripts during hybridization. RESULTS: We demonstrate that although the probes on the U133A GeneChip arrays are identical in sequence to probes designed for the U133 Plus 2.0 arrays the values obtained from an experimental hybridization can be quite different. Nearly half of the probesets in common between the two array types can produce slightly different values from the same sample. Nearly 70% of the individual probes in these probesets produced array specific differences. CONCLUSION: The context of the probe may also contribute some bias to the final measured value of gene expression. At a minimum, this should add an extra level of caution when considering the direct comparison of experiments performed in two microarray formats. More importantly, this suggests that it may not be possible to know which value is the most accurate representation of a biological sample when comparing two formats.

Databases, Nucleic Acid↗
PubMed2006

Mouse genomic representational oligonucleotide microarray analysis: detection of copy number variations in normal and tumor specimens.

Genomic amplifications and deletions, the consequence of somatic variation, are a hallmark of human cancer. Such variation has also been observed between "normal" individuals, as well as in individuals with congenital disorders. Thus, copy number measurement is likely to be an important tool for the analysis of genetic variation, genetic disease, and cancer. We developed representational oligonucleotide microarray analysis, a high-resolution comparative genomic hybridization methodology, with this aim in mind, and reported its use in the study of humans. Here we report the development of a representational oligonucleotide microarray analysis microarray for the genomic analysis of the mouse, an important model system for many genetic diseases and cancer. This microarray was designed based on the sequence assembly MM3, and contains approximately 84,000 probes randomly distributed throughout the mouse genome. We demonstrate the use of this array to identify copy number changes in mouse cancers, as well to determine copy number variation between inbred strains of mice. Because restriction endonuclease digestion of genomic DNA is an integral component of our method, differences due to polymorphisms at the restriction enzyme cleavage sites are also observed between strains, and these can be useful to follow the inheritance of loci between crosses of different strains.

Animals↗
PubMed2005

A hidden Markov model for analyzing ChIP-chip experiments on genome tiling arrays and its application to p53 binding sequences.

MOTIVATION: Transcription factors (TFs) regulate gene expression by recognizing and binding to specific regulatory regions on the genome, which in higher eukaryotes can occur far away from the regulated genes. Recently, Affymetrix developed the high-density oligonucleotide arrays that tile all the non-repetitive sequences of the human genome at 35 bp resolution. This new array platform allows for the unbiased mapping of in vivo TF binding sequences (TFBSs) using Chromatin ImmunoPrecipitation followed by microarray experiments (ChIP-chip). The massive dataset generated from these experiments pose great challenges for data analysis. RESULTS: We developed a fast, scalable and sensitive method to extract TFBSs from ChIP-chip experiments on genome tiling arrays. Our method takes advantage of tiling array data from many experiments to normalize and model the behavior of each individual probe, and identifies TFBSs using a hidden Markov model (HMM). When applied to the data of p53 ChIP-chip experiments from an earlier study, our method discovered many new high confidence p53 targets including all the regions verified by quantitative PCR. Using a de novo motif finding algorithm MDscan, we also recovered the p53 motif from our HMM identified p53 target regions. Furthermore, we found substantial p53 motif enrichment in these regions comparing with both genomic background and the TFBSs identified earlier. Several of the newly identified p53 TFBSs are in the promoter region of known genes or associated with previously characterized p53-responsive genes. SUPPLEMENTARY INFORMATION: Available at the following URL http://genome.dfci.harvard.edu/~xsliu/HMMTiling/index.html.

Amino Acid Motifs↗
PubMed2003

Sequence versus structure for the direct detection of 16S rRNA on planar oligonucleotide microarrays.

A two-probe proximal chaperone detection system consisting of a species-specific capture probe for the microarray and a labeled, proximal chaperone probe for detection was recently described for direct detection of intact rRNAs from environmental samples on oligonucleotide arrays. In this study, we investigated the physical spacing and nucleotide mismatch tolerance between capture and proximal chaperone detector probes that are required to achieve species-specific 16S rRNA detection for the dissimilatory metal and sulfate reducer 16S rRNAs. Microarray specificity was deduced by analyzing signal intensities across replicate microarrays with a statistical analysis-of-variance model that accommodates well-to-well and slide-to-slide variations in microarray signal intensity. Chaperone detector probes located in immediate proximity to the capture probe resulted in detectable, nonspecific binding of nontarget rRNA, presumably due to base-stacking effects. Species-specific rRNA detection was achieved by using a 22-nt capture probe and a 15-nt detector probe separated by 10 to 14 nt along the primary sequence. Chaperone detector probes with up to three mismatched nucleotides still resulted in species-specific capture of 16S rRNAs. There was no obvious relationship between position or number of mismatches and within- or between-genus hybridization specificity. From these results, we conclude that relieving secondary structure is of principal concern for the successful capture and detection of 16S rRNAs on planar surfaces but that the sequence of the capture probe is more important than relieving secondary structure for achieving specific hybridization.

Base Sequence↗
PubMed2006

Transcript mapping with high-density oligonucleotide tiling arrays.

MOTIVATION: High-density DNA tiling microarrays are a powerful tool for the characterization of complete transcriptomes. The two major analytical challenges are the segmentation of the hybridization signal along genomic coordinates to accurately determine transcript boundaries and the adjustment of the sequence-dependent response of the oligonucleotide probes to achieve quantitative comparability of the signal between different probes. RESULTS: We describe a dynamic programming algorithm for finding a globally optimal fit of a piecewise constant expression profile along genomic coordinates. We developed a probe-specific background correction and scaling method that employs empirical probe response parameters determined from reference hybridizations with no need for paired mismatch probes. This combined analysis approach allows the accurate determination of dynamical changes in transcription architectures from hybridization data and will help to study the biological significance of complex transcriptional phenomena in eukaryotic genomes. AVAILABILITY: R package tilingArray at http://www.bioconductor.org.

Algorithms↗
PubMed2004

DNA microarray for rapid detection of mitochondrial DNA haplotypes of chum salmon.

For use in genetic stock identification, we developed an oligonucleotide (DNA) microarray hybridization method for rapid and accurate detection of nucleotide sequence variations in 20 previously identified variable nucleotide sites in about 500 bp within the 5' half of the control region of mitochondrial DNA of chum salmon (Oncorhynchus keta). The method includes immobilization of synthesized oligonucleotides containing respective polymorphic sites on a glass slide precoated with polycarbodiimide resin, a 2-hour hybridization with DNA microarray of biotinylated polymerase chain reaction fragments spanning the 5' variable portion followed by short washing, and visualization of hybridization signals by conventional ABC method and scanner-assisted computation of signal intensity on a computer. The entire process of hybridization and detection was completed within 4 hours. The resulting DNA microarray could detect all of the single nucleotide mutations and therefore could be used to identity the sequence variations defining 30 mtDNA haplotypes of chum salmon as revealed previously by nucleotide sequence analysis.

Animals↗
PubMed2004

Prognostic meta-signature of breast cancer developed by two-stage mixture modeling of microarray data.

BACKGROUND: An increasing number of studies have profiled tumor specimens using distinct microarray platforms and analysis techniques. With the accumulating amount of microarray data, one of the most intriguing yet challenging tasks is to develop robust statistical models to integrate the findings. RESULTS: By applying a two-stage Bayesian mixture modeling strategy, we were able to assimilate and analyze four independent microarray studies to derive an inter-study validated "meta-signature" associated with breast cancer prognosis. Combining multiple studies (n = 305 samples) on a common probability scale, we developed a 90-gene meta-signature, which strongly associated with survival in breast cancer patients. Given the set of independent studies using different microarray platforms which included spotted cDNAs, Affymetrix GeneChip, and inkjet oligonucleotides, the individually identified classifiers yielded gene sets predictive of survival in each study cohort. The study-specific gene signatures, however, had minimal overlap with each other, and performed poorly in pairwise cross-validation. The meta-signature, on the other hand, accommodated such heterogeneity and achieved comparable or better prognostic performance when compared with the individual signatures. Further by comparing to a global standardization method, the mixture model based data transformation demonstrated superior properties for data integration and provided solid basis for building classifiers at the second stage. Functional annotation revealed that genes involved in cell cycle and signal transduction activities were over-represented in the meta-signature. CONCLUSION: The mixture modeling approach unifies disparate gene expression data on a common probability scale allowing for robust, inter-study validated prognostic signatures to be obtained. With the emerging utility of microarrays for cancer prognosis, it will be important to establish paradigms to meta-analyze disparate gene expression data for prognostic signatures of potential clinical use.

Bayes Theorem↗
PubMed2006

Picoeukaryotic plankton diversity at the Helgoland time series site as assessed by three molecular methods.

We analyzed picoeukaryote assemblages in the German Bight at the Helgoland time series site by sequencing cloned eukaryotic 18S rRNA genes in six genetic libraries plus one library from the Orkney Islands from a cruise of opportunity. The libraries were constructed from environmental samples collected at different periods of the year. The same samples were also analyzed using a fingerprinting technique, single-strand conformational polymorphism (SSCP), and DNA microarrays with class-level oligonucleotide probes. One hundred unique clones were analyzed from each library, thus insuring over 85% coverage of the library. The V4 region of the 18S rRNA gene was sequenced from each of these clones, thus providing the most discrimination among the clones. The nonphotosynthetic picoeukaryotic component dominated over the photosynthetic one and was represented by the ciliates at 45% and group II alveolates at 42%. Prasinophytes dominated the photosynthetic group at 40%, but other picoplankton groups, such as bolidomonads and chrysophytes, were also present. Totally novel groups were found in the cryptomonads and in the dinoflagellates. A new algal group sister to the cryptophyte nuclear gene and the glaucocystophytes was also found. These three groups have been found in other picoeukaryotic planktonic clone libraries. SSCP analyses at closer time intervals suggest that clone libraries should be made at weekly intervals if succession in the picoeukaryotic plankton community is to be monitored accurately. A comparison of annual samples suggests thatthere appears to be an annual cycle with regard to species composition. Microarray analysis supported the clone library data and offered a faster means of community analysis, which can be performed with similar accuracy and with higher throughput for a more in-depth analysis.

Animals↗
PubMed2005

A novel method for STR-based DNA profiling using microarrays.

We describe a novel method for rapidly identifying and distinguishing between different DNA sequences using short tandem repeat (STR) analysis and DNA microarrays. The method can be used to deduce identity, length, and number of STRs of the target molecule. We refer to this technique as the "variable-length probe array" method for STR profiling (VLPA). The method involves hybridization of the unknown STR target sequence to a DNA microarray displaying complementary probes that vary in length to cover the range of possible STRs. A post-hybridization enzymatic digestion of the DNA hybrids is then used to selectively remove labeled single-stranded regions of DNA from the microarray surface. The number of repeats in the unknown target is then deduced based on the pattern of target DNA that remains hybridized to the array. This DNA profiling technique is useful for performing forensic analysis to uniquely identify individual humans or other species.

DNA↗
PubMed2006

Kinetics of oligonucleotide hybridization to photolithographically patterned DNA arrays.

The hybridization kinetics of oligonucleotide targets to oligonucleotide probe arrays synthesized using photolithographic fabrication methods developed by Affymetrix have been measured. Values for the fundamental adsorption parameters, k(a), k(d), and K, were determined at both room temperature and 45 degrees C by monitoring the hybridization of fluorescently labeled targets to the array. The values for these parameters and the adsorbed target density (<or=1 pmol/cm(2) at saturation) agree relatively well with published values for arrays fabricated by immobilizing intact probes. The isotherms can be fit well with the Sips model, a generalization of the Langmuir model that allows for multiple binding energies. However, binding to these arrays also displays certain characteristics that may result from the close spacing of probes on the array. At high target concentrations and 22 degrees C, an "overshoot" is observed, wherein a large amount of target binds rapidly and then desorbs to a final plateau. This binding mode may be a result of the unique nature of photolithographically patterned arrays given that targets initially can bind in lower stability binding modes by partially adsorbing to a probe and its neighbor(s), a process that can be viewed as a form of competitive hybridization for overlapping sites on a given probe. Using the values measured for k(a) and k(d), an analytical model that accounts for this behavior is proposed. Alternatively, at 45 degrees C, the adsorption approaches an initial plateau, rather than an overshoot, and then undergoes a "secondary rise" to a final value. A potential explanation for this phenomenon that is compatible with the analysis at lower temperature is offered.

Adsorption↗
PubMed2005

Global analysis of yeast RNA processing identifies new targets of RNase III and uncovers a link between tRNA 5' end processing and tRNA splicing.

We used a microarray containing probes that tile all known yeast noncoding RNAs (ncRNAs) to investigate RNA biogenesis on a global scale. The microarray verified a general loss of Box C/D snoRNAs in the TetO7-BCD1 mutant, which had previously been shown for only a handful of snoRNAs. We also monitored the accumulation of improperly processed flank sequences of pre-RNAs in strains depleted for known RNA nucleases, including RNase III, Dbr1p, Xrn1p, Rat1p and components of the exosome and RNase P complexes. Among the hundreds of aberrant RNA processing events detected, two novel substrates of Rnt1p (the RUF1 and RUF3 snoRNAs) were identified. We also identified a relationship between tRNA 5' end processing and tRNA splicing, processes that were previously thought to be independent. This analysis demonstrates the applicability of microarray technology to the study of global analysis of ncRNA synthesis and provides an extensive directory of processing events mediated by yeast ncRNA processing enzymes.

Gene Expression Regulation, Fungal↗
PubMed2005

Long versus short oligonucleotide microarrays for the study of gene expression in nonhuman primates.

The high degree of sequence similarity between human and nonhuman primate (NHP) genomic DNA suggests that human genome sequence-based DNA microarrays may be used effectively to study gene expression in NHP disease models. In the present study, two distinct commercially available human genome microarray platforms, the Affymetrix HG U133A GeneChip System utilizing Human Genome U133A GeneChips and the Applied Biosystems Expression Array System utilizing the Human Genome Survey Microarray, were used to identify and characterize gene expression changes in the anterior cerebellum of a macaque monkey model of human alcoholism. The Affymetrix microarray consists of eleven short oligonucleotide probe sets for each gene while the Applied Biosystems Microarray uses a single long oligonucleotide per gene. Cross-mapping of probes revealed a total of 11,542 genes that are represented on both microarray platforms. Absolute measures of gene expression ("present calls") from the cerebellum RNA samples were 65-70% (Applied Biosystems Expression Array System) and 27-30% (AffymetrixGeneChip System) among these common gene targets. Analysis of variance (ANOVA; p<0.05; >1.2 fold change; detected on at least 50% of the arrays) indicated 932 and 515 differentially expressed genes for the Applied Biosystems and Affymetrix microarrays, respectively. Significance analysis of microarrays (SAM) identified 255 significant genes at 5% false discovery rate (FDR) for the Applied Biosystems data set and five significant genes at 60% FDR (minimum FDR) for the Affymetrix data set. TaqMan assay-based real-time PCR validation of a number of differentially-expressed genes yielded results that agreed well with the array data in the majority of comparisons. This study demonstrates that human sequence-based DNA arrays can be used effectively to detect differential gene expression in an NHP disease model and provides evidence that the use of this long oligonucleotide-based microarray platform may be more suitable for cross-species gene expression studies than a short oligonucleotide-based system.

Alcohol Drinking↗
PubMed2006

Implication of SSAT by gene expression and genetic variation in suicide and major depression.

CONTEXT: A large body of evidence suggests that predisposition to suicide, an important public health problem, is mediated to a certain extent by neurobiological factors. OBJECTIVE: To investigate patterns of expression in suicide with and without major depression and to identify new molecular targets that may play a role in the neurobiology of these conditions. DESIGN: Brain gene expression analysis was performed using the Affymetrix HG-U133 chipset in the orbital cortex (Brodmann area [BA] 11), the dorsolateral prefrontal cortex (BA8/9), and motor cortex (BA4). Subsequent studies were carried out in independent samples from adjacent areas to validate positive findings, confirm their relevance at the protein level, and investigate possible effects of genetic variation. SUBJECTS: We investigated 12 psychiatrically normal control subjects and 24 suicide victims, including 16 with and 8 without major depression, in the brain gene expression analysis, validation, and protein studies. The genetic studies included 181 suicide completers and 80 psychiatrically normal controls. All subjects investigated were male and of French Canadian origin. MAIN OUTCOME MEASURES: Gene expression measures from microarray, semiquantitative reverse transcription-polymerase chain reaction, immunohistochemistry, and Western blot analyses. RESULTS: Twenty-six genes were selected because of the consistency of their expression pattern (fold change, >1.3 in either direction [P<or=.01] in at least 2 regions). The spermine/spermidine N(1)-acetyltransferase gene (SSAT) was successfully validated by reverse transcription-polymerase chain reaction, immunohistochemistry, and Western blot analyses. A variant located in the SSAT polyamine-responsive element regulatory region (SSAT342A/C) demonstrated a significant effect of genotype on SSAT brain expression levels (F(1) = 5.34; P = .02). Further investigation of this variant in an independent sample of 181 male suicide completers and 80 male controls showed a higher frequency of the SSAT342C allele among suicide cases (odds ratio, 2.7; 95% confidence interval, 1.4-5.3; P = .005), suggesting that this allele may increase predisposition to suicide. CONCLUSIONS: These data suggest a role for SSAT, the rate-limiting enzyme in the catabolism of polyamines, in suicide and depression and a role for the SSAT342 locus in the regulation of SSAT gene expression.

Acetyltransferases↗