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Frontiers in Plant Science 2022Rice ( L.) is one of the important staple foods for human consumption and livestock use. As a complex quality trait, free amino acid (FAA) content in rice is of...
Rice ( L.) is one of the important staple foods for human consumption and livestock use. As a complex quality trait, free amino acid (FAA) content in rice is of nutritional importance. To dissect the genetic mechanism of FAA level, five amino acids' (Val, Leu, Ile, Arg, and Trp) content and 4,325,832 high-quality SNPs of 448 rice accessions were used to conduct genome-wide association studies (GWAS) with nine different methods. Of these methods, one single-locus method (GEMMA), seven multi-locus methods (mrMLM, pLARmEB, FASTmrEMMA, pKWmEB, FASTmrMLM, ISIS EM-BLASSO, and FarmCPU), and the recent released 3VmrMLM were adopted for methodological comparison of quantitative trait nucleotide (QTN) detection and identification of stable quantitative trait nucleotide loci (QTLs). As a result, 987 QTNs were identified by eight multi-locus GWAS methods; FASTmrEMMA detected the most QTNs (245), followed by 3VmrMLM (160), and GEMMA detected the least QTNs (0). Among 88 stable QTLs identified by the above methods, 3VmrMLM has some advantages, such as the most common QTNs, the highest LOD score, and the highest proportion of all detected stable QTLs. Around these stable QTLs, candidate genes were found in the GO classification to be involved in the primary metabolic process, biosynthetic process, and catalytic activity, and shown in KEGG analysis to have participated in metabolic pathways, biosynthesis of amino acids, and tryptophan metabolism. Natural variations of candidate genes resulting in the content alteration of five FAAs were identified in this association panel. In addition, 95 QTN-by-environment interactions (QEIs) of five FAA levels were detected by 3VmrMLM only. GO classification showed that the candidate genes got involved in the primary metabolic process, transport, and catalytic activity. Candidate genes of QEIs played important roles in valine, leucine, and isoleucine degradation (QEI_09_03978551 and candidate gene in the Leu dataset), tryptophan metabolism (QEI_01_00617184 and candidate gene in the Trp dataset), and glutathione metabolism (QEI_12_09153839 and candidate gene in the Arg dataset) pathways through KEGG analysis. As an alternative of the multi-locus GWAS method, these findings suggested that the application of 3VmrMLM may provide new insights into better understanding FAA accumulation and facilitate the molecular breeding of rice with high FAA level.
PubMed: 36420042
DOI: 10.3389/fpls.2022.1048860 -
Alzheimer Disease and Associated...Executive function (EF) involves a general cognitive process linked to strategic organization and control of complex goal-oriented tasks. In young-onset dementia (YOD),...
INTRODUCTION
Executive function (EF) involves a general cognitive process linked to strategic organization and control of complex goal-oriented tasks. In young-onset dementia (YOD), especially Alzheimer's disease, the symptoms that stand out in the initial stage are deficits in attention, visual-spatial function, praxis, and language. The present study aims to investigate what components of EF differ in young and late-onset dementia (LOD) and its impact on awareness and its domains.
METHODS
Using a cross-sectional design, we included 44 people with YOD and 70 with LOD. We assessed awareness and its domains, cognition, dementia severity, EF, functionality, and neuropsychiatric symptoms.
RESULTS
The YOD group was more impaired in general cognition ( P =0.017) and had a worse performance in Wechsler Digit Span Backward (DSB) ( P =0.007) and Phonemic fluency task (FAS) ( P =0.046) tests. In the LOD group, deficits in EF had a greater impact on awareness and on most domains (awareness total score, cognitive functioning and health condition, functional activity impairments and social function).
CONCLUSIONS
Our study findings support the heterogeneity of awareness, not only with regard to the difference between the domains and the measures of EF, but also to the groups studied.
Topics: Humans; Dementia; Executive Function; Cross-Sectional Studies; Age of Onset; Alzheimer Disease
PubMed: 37561987
DOI: 10.1097/WAD.0000000000000561 -
Asian Journal of Psychiatry Dec 2020Older adults with depression often have cognitive deficits contributing to higher morbidity and increased risk for conversion to dementia. Research on this area is...
BACKGROUND
Older adults with depression often have cognitive deficits contributing to higher morbidity and increased risk for conversion to dementia. Research on this area is limited from India.
OBJECTIVE
The objective of the current study is to examine the neuropsychological measures in older adults with Late-onset depression (LOD) compared to healthy controls (HC).
METHOD
Sample included older adults with depression as per DSM-IV TR criteria seeking treatment from Geriatric Clinic and Services, National Institute of Mental Health and Neurosciences (NIMHANS). Geriatric depression scale, Montgomery Asberg depression rating scale and Hamilton anxiety rating scale were applied to screen and measure the severity of depression. Comprehensive assessment of neurocognitive function was done using NIMAHNS Neuropsychological Battery for Elderly (NNBE, 2013).
RESULTS
Sample included 76 LOD patients and 76 healthy controls (HC) who were matched for age, gender and education. The mean age of onset of illness was 63.17(SD-6.54) years and median duration of total illness was 29.5 months. In the standard assessments, the mean score on GDS was 9.28 (SD-3.32) and MADRS was 18.88 (SD-6.07). The LOD group had lower Hindi Mental Status Examination (HMSE) score compared to HC (28.64 ± 2.09 vs 30.05 ± 1.26, p < 0.001). Compared to HC, LOD group performed poorly on tasks of attention, executive function, verbal and visual memory, verbal fluency and visuo-spatial skills. Recognition memory and logical memory were relatively preserved in LOD compared to HC.
DISCUSSION AND CONCLUSION
Cognitive deficits were seen predominantly in attention and executive function, visuo-spatial skills and memory similar to previous studies. It is advisable to routinely assess cognitive symptoms in older adults presenting with depression.
Topics: Aged; Cognition Disorders; Depression; Executive Function; Humans; India; Neuropsychological Tests
PubMed: 33271715
DOI: 10.1016/j.ajp.2020.102435 -
American Journal of Medical Genetics.... Apr 2017Sex influences risk for opioid dependence (OD). We hypothesized that sex might interact with genetic loci that influence the risk for OD. Therefore we performed an...
Sex influences risk for opioid dependence (OD). We hypothesized that sex might interact with genetic loci that influence the risk for OD. Therefore we performed an analysis to identify sex-specific genomic susceptibility regions for OD using linkage. Over 6,000 single nucleotide polymorphism (SNP) markers were genotyped for 1,758 African- and European-American (AA and EA) individuals from 739 families, ascertained via affected sib-pairs with OD and/or cocaine dependence. Autosomewide non-parametric linkage scans, stratified by sex and population, were performed. We identified one significant linkage region, segregating with OD in EA men, at 71.1 cM on chromosome 4 (LOD = 3.29; point-wise P = 0.00005; empirical autosome-wide P = 0.042), which significantly differed from the linkage signal at the same location in EA women (empirical P = 0.002). Three suggestive linkage signals were identified at 181.3 cM on chromosome 7 (LOD = 2.18), 104 cM on chromosome 11 (LOD = 1.85), and 60.9 cM on chromosome 16 (LOD = 1.93) in EA women. In AA men, four suggestive linkage signals were detected at 201.1 cM on chromosome 3 (LOD = 2.32), 152.9 cM on chromosome 6 (LOD = 1.86), 16.8 cM on chromosome 7 (LOD = 1.95), and 36.1 cM on chromosome 17 (LOD = 1.99). The significant region, mapping to 4q12-4q13.1, harbors several OD candidate genes with interconnected functionality, including VEGFR, CLOCK, PDCL2, NMU, NRSF, and IGFBP7. In conclusion, these results provide an evidence for the existence of sex-specific and population-specific differences in OD. Furthermore, these results provide positional information that will facilitate the use of targeted next-generation sequencing to search for genes that contribute to sex-specific differences in OD. © 2016 Wiley Periodicals, Inc.
Topics: Adult; Black or African American; Black People; Chromosome Mapping; Cocaine-Related Disorders; Female; Genetic Linkage; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Lod Score; Male; Middle Aged; Opioid-Related Disorders; Polymorphism, Single Nucleotide; Risk Factors; Sex Factors; White People
PubMed: 27762075
DOI: 10.1002/ajmg.b.32507 -
Clinica Chimica Acta; International... Aug 2023The Enhanced Liver Fibrosis (ELF) Test comprises 3 direct serum markers of fibrosis-hyaluronic acid (HA), amino-terminal pro-peptide of type III procollagen (PIIINP),...
BACKGROUND
The Enhanced Liver Fibrosis (ELF) Test comprises 3 direct serum markers of fibrosis-hyaluronic acid (HA), amino-terminal pro-peptide of type III procollagen (PIIINP), and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1)-whose results are combined in an algorithm to generate the ELF score. Outside the U.S., the ELF Test and score are CE marked for assessment of liver fibrosis severity in patients with signs, symptoms, or risk factors of chronic liver disease to support diagnosis of fibrosis staging or prognosis for likelihood of progression to cirrhosis and liver-related clinical events. In the U.S., the FDA granted de novo marketing authorization to aid prognostic evaluation of disease progression (to cirrhosis and liver-related clinical events) in nonalcoholic steatohepatitis patients with advanced liver fibrosis. We describe the analytical performance of the ELF analytes and score on the Atellica® IM Analyzer.
METHODS
Clinical and Laboratory Standards Institute protocols were followed for detection capability (limits of blank [LoB], detection [LoD], and quantitation [LoQ]), precision, interference, linearity, hook effect, and ELF reference interval.
RESULTS
All parameters met predetermined requirements: HA (LoB 1.00 ng/mL, LoD 2.00 ng/mL, LoQ 3.00 ng/mL); PIIINP (LoB 0.50 ng/mL, LoD 0.75 ng/mL, LoQ 1.00 ng/mL); TIMP-1 (LoB 3.0 ng/mL, LoD 4.0 ng/mL, LoQ 5.0 ng/mL). Across the 3 assays, repeatability was ≤5.4% CV; within-lab precision was ≤8.5% CV. ELF score repeatability was ≤0.6% CV, within-lab precision ≤1.3% CV, and reproducibility ≤1.1% CV. Good correlation was obtained between the Atellica IM ELF and ADVIA Centaur ELF Tests (y = 1.01x - 0.22, r = 0.997). Assays were linear across analytical measuring ranges.
CONCLUSIONS
Analytical performance validation results for the ELF Test and ELF score were excellent making the test acceptable for routine clinical use.
Topics: Humans; Tissue Inhibitor of Metalloproteinase-1; Reproducibility of Results; Liver Cirrhosis; Fibrosis; Liver; Biomarkers; Hyaluronic Acid
PubMed: 37390944
DOI: 10.1016/j.cca.2023.117461 -
Methods in Molecular Biology (Clifton,... 2015Since the breakthrough of genome-wide association studies and genetic studies of common complex diseases like celiac disease have been able to finally identify... (Review)
Review
Since the breakthrough of genome-wide association studies and genetic studies of common complex diseases like celiac disease have been able to finally identify reproducible gene regions affecting risk of developing disease. Before it was possible to perform genome-wide association analysis, the field struggled with genome-wide linkage analysis to identify gene regions. Genome-wide linkage had been very successful in identifying genes underlying monogenic diseases, but common complex polygenic diseases did not prove so tractable. This chapter will describe the genome-wide methods available for genetic analyses of families today and compare these with the previous analyses performed in the 1990s and early twenty-first century.
Topics: Adult; Age of Onset; Celiac Disease; Child; Genetic Linkage; Genome-Wide Association Study; HLA Antigens; Humans
PubMed: 26498610
DOI: 10.1007/978-1-4939-2839-2_4 -
Journal of Autoimmunity Aug 2016Familial autoimmunity and polyautoimmunity represent extreme phenotypes ideal for identifying major genomic variants contributing to autoimmunity. Whole exome sequencing...
OBJECTIVES
Familial autoimmunity and polyautoimmunity represent extreme phenotypes ideal for identifying major genomic variants contributing to autoimmunity. Whole exome sequencing (WES) and linkage analysis are well suited for this purpose due to its strong resolution upon familial segregation patterns of functional protein coding and splice variants. The primary objective of this study was to identify potentially autoimmune causative variants using WES data from extreme pedigrees segregating polyautoimmunity phenotypes.
METHODS
DNA of 47 individuals across 10 extreme pedigrees, ascertained from probands affected with polyautoimmunity and familial autoimmunity, were selected for WES. Variant calls were obtained through Genome Analysis Toolkit. Filtration and prioritization framework to identify mutation(s) were applied, and later implemented for genetic linkage analysis. Sanger sequencing corroborated variants with significant linkage.
RESULTS
Novel and mostly rare variants harbored in SRA1, MLL4, ABCB8, DHX34 and PLAUR showed significant linkage (LOD scores are >3.0). The strongest signal was in SRA1, with a LOD score of 5.48. Network analyses indicated that SRA1, PLAUR and ABCB8 contribute to regulation of apoptotic processes.
CONCLUSIONS
Novel and rare variants in genetic linkage with polyautoimmunity were identified throughout WES. Genes harboring these variants might be major players of autoimmunity.
Topics: ATP-Binding Cassette Transporters; Autoimmunity; Base Sequence; Carrier Proteins; DNA-Binding Proteins; Exome; Family Health; Female; Gene Regulatory Networks; Genetic Predisposition to Disease; Genomics; Histone-Lysine N-Methyltransferase; Humans; Lod Score; Male; Mutation; Pedigree; Phenotype; RNA Helicases; Receptors, Urokinase Plasminogen Activator; Sequence Analysis, DNA
PubMed: 27209085
DOI: 10.1016/j.jaut.2016.05.003 -
Gaceta Medica de Mexico 2019The first draft of the human genome sequencing published in 2001 reported a large number of single nucleotide polymorphisms (SNPs). Given that these polymorphisms could... (Review)
Review
The first draft of the human genome sequencing published in 2001 reported a large number of single nucleotide polymorphisms (SNPs). Given that these polymorphisms could practically represent all the variability involved in the susceptibility, protection, severity, among other aspects, of various common diseases, as well as in their response to medications, it was thought that they might be "the biomarkers of choice" in personalized genomic medicine. With the new information obtained from the sequencing of a larger number of genomes, we have understood that SNPs are only an important part of the genetic markers involved in these traits. In addition to SNPs, other variants have been identified, such as insertions/deletions (INDELs) and copy number variants (CNVs), which - in addition to classic variable number tandem repeats (VNTRs) and short tandem repeats (STRs) - originate or contribute to the development of diseases. The use of these markers has served to identify regions of the genome involved in Mendelian diseases (one gene-one disease) or genes directly associated with multifactorial diseases. This review has the purpose to describe the role of STRs, VNTRs, SNPs, CNVs and INDELs in linkage and association studies and their role in Mendelian and multifactorial diseases.
Topics: Disease; Gene Deletion; Genetic Markers; Genetic Variation; Genome, Human; Humans; Lod Score; Mutagenesis, Insertional; Mutation; Polymorphism, Single Nucleotide; Tandem Repeat Sequences
PubMed: 32091015
DOI: 10.24875/GMM.M20000333 -
Methods in Molecular Biology (Clifton,... 2017It has been documented that there exist some errors in most large genotype datasets and that an error rate of 1-2% is sufficient to lead to the distortion of map...
It has been documented that there exist some errors in most large genotype datasets and that an error rate of 1-2% is sufficient to lead to the distortion of map distance as well as a false conclusion of linkage (Abecasis et al., Eur J Hum Genet 9:130-134, 2001), therefore one needs to ensure that the data are as clean as possible. On the other hand, the process of data cleaning is tedious and demands effort and experience. O'Connell and Weeks implemented four error-checking algorithms in computer software called PedCheck. In this chapter, the four algorithms implemented in PedCheck are discussed with a focus on the genotype-elimination method. Furthermore, an example for four levels of error checking permitted by PedCheck is provided with the required input files. In addition, alternative algorithms implemented in other statistical computing programs are also briefly discussed.
Topics: Algorithms; Female; Genotype; Genotyping Techniques; Humans; Male; Odds Ratio; Pedigree; Software
PubMed: 28980239
DOI: 10.1007/978-1-4939-7274-6_2 -
East Asian Archives of Psychiatry :... Sep 2019This study aimed to examine the association between five personality traits and late-onset depression in Hong Kong older people.
OBJECTIVE
This study aimed to examine the association between five personality traits and late-onset depression in Hong Kong older people.
METHODS
This cross-sectional study included a convenience sample of 40 older people with late-onset depression (LOD) and 54 non-depressed elderly controls. The patients were assessed using the NEO Five Factor Inventory (for personality), the Hamilton Depression Rating Scale (for depression severity), the Mini-Mental State Examination (for cognitive function), the Lawton Instrumental Activities of Daily Living (for functioning), and the Cumulative Illness Rating Scale (for number of physical illnesses).
RESULT
The LOD group had a higher Hamilton Depression Rating Scale score (18.9 vs 3.7, p < 0.001), lower Mini Mental State Examination score (24.9 vs 26.4, p = 0.004), and lower Instrumental Activities of Daily Living scale score (21.9 vs 23.7, p = 0.013). On the NEO Five Factor Inventory, the LOD group had a higher neuroticism score (30.7 vs 17.5, p < 0.001) and lower scores on extraversion (19.0 vs 26.4, p < 0.001), openness (18.9 vs 21.5, p = 0.026), and conscientiousness (29.1 vs 33.8, p < 0.001). Neuroticism was the only significant predictor of LOD (odds ratio = 2.325, p = 0.001) and the only significant factor associated with depression severity (β = 0.581, p = 0.003).
CONCLUSIONS
The personality trait of neuroticism is associated with LOD and its severity. Assessment of personality traits should be included in the assessment of people with depression.
Topics: Activities of Daily Living; Aged; Aged, 80 and over; Cross-Sectional Studies; Depression; Female; Hong Kong; Humans; Late Onset Disorders; Male; Personality; Personality Inventory; Psychiatric Status Rating Scales
PubMed: 31566183
DOI: 10.12809/eaap1761