| 1. |
- Ahsan, Muhammad, et al.
(författare)
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Identification of candidate genes and mutations in QTL regions for chicken growth using bioinformatic analysis of NGS and SNP-ChiP data
- 2013
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Quantitative trait loci (QTL) mapping is a first step to identify chromosomal regions harboring genetic polymorphisms that regulate complex traits. Searching causative mutations for observed effects is sometimes a daunting task as even after fine mapping of the QTL, millions of base pairs including many genes will typically need to be explored. There is thus a great need for efficient bioinformatics strategies to trace the causative mutation(s). Here, we searched for gene transcripts along with mutations regulating body weight at 56 days traits in the Virginia chicken lines – an experimental population comprising two lines that have been divergently selected for 56 days body weight for more than 50 generations. Several QTL regions have been mapped in an F2 intercross between the lines, and the regions have subsequently been replicated and fine mapped using an Advanced Intercross Line (AIL). Candidate transcripts and mutations were here sought in the parts of the QTL regions where the highest genetic divergence between the High-Weight selected (HWS) and Low-Weight selected (LWS) lines was observed. Such regions, 47 Mbp or 35% of the actual QTL regions, were identified by comparing the allele frequencies in the genomes of the HWS and LWS lines using both individual 60K SNP chip genotyping of birds and analysis of read proportions with 12X ABI SOLID genome resequencing of DNA pools. Gene transcripts in the target segments, obtained using the Ensembl genome browser 67, were analyzed with DAVID bioinformatic database to investigate their role in any growth-related functions. Single nucleotide polymorphisms (SNPs) in target segments obtained from resequencing data were analyzed with Variant Effect Predictor (VEP) tool to find their location and functional consequences in gene transcripts. Non-synonymous SNPs (nsSNPs) were scored for their effects on protein function with PASE software (Li et al., submitted). Finally, we present most important candidate gene transcripts from each QTL segment for further functional validation. For example, the cysteine rich transmembrane BMP regulator 1 (chordin-like) gene has growth factor binding and cell growth functions. It carries a nsSNP with high allele frequency difference (0.97) between lines, PASE (0.67) and conservation scores (0.63). Another candidate, glucagon is involved in anorexia and appetite regulation carrying a CpG mutation with high allele frequency difference (0.87) between lines.
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| 2. |
- Ahsan, Muhammad, et al.
(författare)
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Identification of candidate genes and mutations in QTL regions for chicken growth using bioinformatic analysis of NGS and SNP-chip data.
- 2013
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Mapping of chromosomal regions harboring genetic polymorphisms that regulate complex traits is usually followed by a search for the causative mutations underlying the observed effects. This is often a challenging task even after fine mapping, as millions of base pairs including many genes will typically need to be investigated. Thus to trace the causative mutation(s) there is a great need for efficient bioinformatic strategies. Here, we searched for genes and mutations regulating growth in the Virginia chicken lines - an experimental population comprising two lines that have been divergently selected for body weight at 56 days for more than 50 generations. Several quantitative trait loci (QTL) have been mapped in an F2 intercross between the lines, and the regions have subsequently been replicated and fine mapped using an Advanced Intercross Line. We have further analyzed the QTL regions where the largest genetic divergence between the High-Weight selected (HWS) and Low-Weight selected (LWS) lines was observed. Such regions, covering about 37% of the actual QTL regions, were identified by comparing the allele frequencies of the HWS and LWS lines using both individual 60K SNP chip genotyping of birds and analysis of read proportions from genome resequencing of DNA pools. Based on a combination of criteria including significance of the QTL, allele frequency difference of identified mutations between the selected lines, gene information on relevance for growth, and the predicted functional effects of identified mutations we propose here a subset of candidate mutations of highest priority for further evaluation in functional studies. The candidate mutations were identified within the GCG, IGFBP2, GRB14, CRIM1, FGF16, VEGFR-2, ALG11, EDN1, SNX6, and BIRC7 genes. We believe that the proposed method of combining different types of genomic information increases the probability that the genes underlying the observed QTL effects are represented among the candidate mutations identified.
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| 3. |
- Carlborg, Andreas, et al.
(författare)
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Attempted suicide predicts suicide risk in schizophrenia spectrum psychosis
- 2010
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 64:1, s. 68-72
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: People with schizophrenia have an increased risk of suicide and attempted suicide is suggested to be an important risk factor.AIM: Our objective was to assess the cumulative survival, predictive values and odds ratios of attempted suicide for suicide in a long-term cohort of patients with schizophrenia spectrum psychosis with and without previous attempted suicide.METHOD: Inpatients (n=224) hospitalized with schizophrenia spectrum psychosis were followed for a mean of 25 years. All patients were followed up for causes of death. Information on suicide attempt before the end of the observation period was retrieved from medical records.RESULTS: Eight percent died by suicide during the follow-up. Eighteen percent of suicide attempters died by suicide. Two percent of non-attempters died by suicide. There was a strong association between previous suicide attempt and suicide in men and women. Odds ratio for attempters vs. non-attempters was 10. Suicide risk was almost three times higher in male than female suicide attempters.CONCLUSION: Previous attempted suicide is an important risk factor for suicide in both men and women with schizophrenia spectrum psychosis, particularly in male suicide attempters. The suicide risk remains high over a long period. Continuous assessment of risk factors and appropriate treatment are crucial for this patient group to prevent suicide.
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| 4. |
- Carlborg, Andreas, et al.
(författare)
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CSF kynurenic acid and suicide risk in schizophrenia spectrum psychosis
- 2013
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 205:1-2, s. 165-7
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Tidskriftsartikel (refereegranskat)abstract
- Relationships between concentrations of cerebrospinal fluid (CSF) kynurenic acid (KYNA) and suicidal behavior were evaluated in 59 patients with psychosis after 22 years of follow-up. Three patients died from suicide and nine patients had a history of attempted suicide. Patients with attempted suicide had significantly lower concentrations of CSF KYNA.
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| 5. |
- Carlborg, Andreas, et al.
(författare)
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Early death and CSF monoamine metabolites in schizophrenia spectrum psychosis
- 2011
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 65:2, s. 101-5
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Patients with schizophrenia have higher rates of mortality than the general population. Lower concentrations of the cerebrospinal fluid (CSF) monoamine metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) have been associated with suicidal, aggressive and impulsive behavior. Mortality has been suggested as a measure of impulsivity and a relationship between early death and lower concentrations of CSF monoamine metabolites has been reported but the studies are few with short periods of follow-up and small numbers.AIM: The objective of this study was to investigate a relationship between early death and concentrations of CSF 5-HIAA and HVA.METHODS: Three hundred and eighty-five inpatients with schizophrenia spectrum psychosis were lumbar punctured in a standardized manner and followed for a median of 26 years. Patients were searched to identify those who had died. Causes of death were obtained from the Causes of Death Register.RESULTS: During the time of follow-up, 97 patients died. Schizophrenia spectrum psychosis patients died at an earlier age from both natural and unnatural causes of death. No significant associations were found between CSF 5-HIAA and HVA concentrations and non-suicidal death. Attempted suicide was not a risk factor for non-suicidal death at younger age.CONCLUSION: Patients with schizophrenia spectrum psychosis die at an earlier age from both natural and unnatural causes of death. Attempted suicide is not a risk factor for non-suicidal death at younger age. Low concentrations of CSF HVA and 5-HIAA were not a risk factor for non-suicidal death at younger age in schizophrenia spectrum psychosis.
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| 6. |
- Carlborg, Andreas, et al.
(författare)
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Suicide in schizophrenia
- 2010
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Ingår i: Expert Review of Neurotherapeutics. - : Informa UK Limited. - 1473-7175 .- 1744-8360. ; 10:7, s. 1153-64
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Forskningsöversikt (refereegranskat)abstract
- Schizophrenia is a disorder with an estimated suicide risk of 4-5%. Many factors are involved in the suicidal process, some of which are different from those in the general population. Clinical risk factors include attempted suicide, depression, male gender, substance abuse and hopelessness. Biosocial factors, such as a high intelligence quotient and high level of premorbid function, have also been associated with an increased risk of suicide in patients with schizophrenia. Suicide risk is especially high during the first year after diagnosis. Many of the suicides occur during hospital admission or soon after discharge. Management of suicide risk includes both medical treatment and psychosocial interventions. Still, risk factors are crude; efforts to predict individual suicides have not proved useful and more research is needed.
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| 7. |
- Nordenskjöld, Axel, 1977-, et al.
(författare)
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Continuation Electroconvulsive Therapy With Pharmacotherapy Versus Pharmacotherapy Alone for Prevention of Relapse of Depression A Randomized Controlled Trial
- 2013
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Ingår i: Journal of ECT. - : Lippincott Williams & Wilkins. - 1095-0680 .- 1533-4112. ; 29:2, s. 86-92
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The primary aim of the study was to test the hypothesis that relapse prevention with continuation electroconvulsive therapy (ECT) plus pharmacotherapy is more effective than pharmacotherapy alone after a course of ECT for depression. Methods: A multicenter, nonblinded, randomized controlled trial with 2 parallel groups was performed from 2008 to 2012 in 4 hospitals in Sweden. Patients eligible had unipolar or bipolar depression and had responded to a course of ECT. The patients (n = 56) were randomly assigned (1: 1) to receiving either 29 treatments of continuation ECT with pharmacotherapy or pharmacotherapy alone for 1 year. The pharmacotherapy consisted of antidepressants (98%), lithium (56%), and antipsychotics (30%). The main outcome was relapse of depression within 1 year. Relapse was defined as 20 or more points on the Montgomery Asberg Depression Rating Scale or inpatient psychiatric care or suicide or suspected suicide. All 56 patients randomized were analyzed according to an intention to treat analysis. Results: Sixty-one percent of the patients treated with pharmacotherapy versus 32% of the patients treated with ECT plus pharmacotherapy relapsed within 1 year (P = 0.036). The Cox proportional hazard ratio was 2.32 (1.03-5.22). Cognitive function and memory measures were stable for patients without relapse in both groups. One suspected suicide and 3 suicide attempts by intoxication occurred, all in the pharmacotherapy-alone group. Conclusions: The post-ECT relapse rates were substantial in both treatment groups with a statistically significant advantage for combined treatment with pharmacotherapy and continuation ECT. Further studies are needed to define indications for continuation ECT, pharmacotherapy, and their combination.
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