Genetic characteristics and forensic features of Xibe ethnic group revealed via extended set of Y-STRs.

BACKGROUND: Xibe is the fifth largest minority population of Liaoning province. Predominately they live in Liaoning province (69.52%), followed by Xinjiang (18.06%), Heilongjiang (3.99%), Jilin (1.63%) and Inner Mongolia provinces (1.57%). AIM: To provide an updated and precise population database on an extended set of Y STRs not available before and explore the forensic characteristics of 26 Y chromosomal STRs. SUBJECTS & METHODS: In this study, we genotyped 406 unrelated Xibe male individuals from Liaoning province using Goldeneye® 26Y System kit and calculated the forensic parameters of these 26 Y STRs loci. RESULTS: All haplotypes generated for 406 Xibe samples using Goldeneye® 26Y kit were unique with a discrimination capacity (DC) of 1. On restricting the haplotypes to the Y-filer® set of 17 Y-STRs, we observed 392 haplotypes. Among them 93.53% (380) were unique with a DC of 0.9655 and haplotype diversity (HD) of 0.9998, showing high discrimination power of the extended set of markers in this population. Allelic frequencies ranged from 0.0024 to 0.7684 across 26 Y STRs loci. DYS385 showed the highest gene diversity (0.9691) among all markers. CONCLUSION: According to pairwise RST genetic distances among Xibe populations from China, the Liaoning Xibe population showed the closest genetic distance (0.0035) followed by Xinjiang Xibe population (0.0218). Multidimensional scaling (MDS) analysis among Xibe and 29 other Chinese populations showed that local populations such as Manchu from Liaoning and Han from Beijing had a close affinity while Tibetans from Aba, China, were most distant from Xibe populations. Moreover, 12 individuals showed a null allele at DYS448 in Xibe population samples. We submitted Y-STRs data in the Y-Chromosome Haplotype Reference Database (YHRD) for future forensic and other usage.

Phylogenetic relationship and genetic history of Central Asian Kazakhs inferred from Y-chromosome and autosomal variations.

The Xinjiang Uyghur Autonomous Region of China (XUARC) with 47 ethnic groups is a very colorful ethnic region of China, harboring abundant genetic and cultural diversity. The Kazakhs are the third largest ethnic group (7.02%) after Uyghur (46.42%) and Han (38.99%) in Xinjiang, but their genetic diversity and forensic characterization are poorly understood. In the current study, we genotyped 15 autosomal short tandem repeat (STR) loci and ten Y-STRs in 889 individuals (659 male and 230 female) collected from Kazak population of the Ili Kazak Autonomous Prefecture using AGCU Expressmarker 16 and 10Y-STR Kit (EX16 + 10Y). For autosomal STRs, we observed a total of 174 different alleles ranging from 6 to 34.2 repeat units and FGA showed the greatest power of discrimination (20 alleles) in Ili Kazakh population. We have not observed departures from Hardy-Weinberg equilibrium (HWE) after sequential Bonferroni correction and only found a minimal departure from linkage equilibrium (LE) for a very small number of pairwise combinations of loci. The combined power of exclusion (CPE) was 0.99999998395 and combined power of discrimination (CPD) was 99.999999999999999798%. For Y-STRs, we observed a total of 496 different haplotypes in these ten Y-STR loci. The gene diversities ranged from 0.5023 (DYS391) to 0.8357 (DYS385a/b). The overall haplotype diversity (GD) was 0.9985 with random matching probability (RMP) of 0.0015. The results of population genetic analysis based on both autosomal and Y-chromosome STRs demonstrated that the genetic affinity among populations is generally consistent with ethnic, linguistic, and continental geographical classifications.

Effects of HTR1B 3' region polymorphisms and functional regions on gene expression regulation.

BACKGROUND: The HTR1B gene encodes the 5-hydroxytryptamine (5-HT1B) receptor, which is involved in a variety of brain activities and mental disorders. The regulatory effects of non-coding regions on genomic DNA are one of many reasons for the cause of genetic-related diseases. Post-transcriptional regulation that depends on the function of 3' regulatory regions plays a particularly important role. This study investigated the effects, on reporter gene expression, of several haplotypes of the HTR1B gene (rs6297, rs3827804, rs140792648, rs9361234, rs76194807, rs58138557, and rs13212041) and truncated fragments in order to analyze the function of the 3' region of HTR1B. RESULTS: We found that the haplotype, A-G-Del-C-T-Ins-A, enhanced the expression level compared to the main haplotype; A-G-Del-C-G-Ins-A; G-G-Del-C-G-Ins-G decreased the expression level. Two alleles, rs76194807T and rs6297G, exhibited different relative luciferase intensities compared to their counterparts at each locus. We also found that + 2440 ~ + 2769 bp and + 1953 ~ + 2311 bp regions both had negative effects on gene expression. CONCLUSIONS: The 3' region of HTR1B has a regulatory effect on gene expression, which is likely closely associated with the interpretation of HTR1B-related disorders. In addition, the HTR1B 3' region includes several effector binding sites that induce an inhibitory effect on gene expression.

Functional polymorphisms and transcriptional analysis in the 5' region of the human serotonin receptor 1B gene (HTR1B) and their associations with psychiatric disorders.

BACKGROUND: The 5-hydroxytryptamine 1B receptor (5-HT1B) plays an essential role in the serotonin (5-HT) system and is widely involved in a variety of brain activities. HTR1B is the gene encoding 5-HT1B. Genome-wide association studies have shown that HTR1B polymorphisms are closely related to multiple mental and behavioral disorders; however, the functional mechanisms underlying these associations are unknown. This study investigated the effect of several HTR1B haplotypes on regulation of gene expression in vitro and the functional sequences in the 5' regulatory region of HTR1B to determine their potential association with mental and behavioral disorders. METHODS: Six haplotypes consisting of rs4140535, rs1778258, rs17273700, rs1228814, rs11568817, and rs130058 and several truncated fragments of the 5' regulatory region of HTR1B were transfected into SK-N-SH and HEK-293 cells. The relative fluorescence intensities of the different haplotypes and truncated fragments were detected using a dual-luciferase reporter assay system. RESULTS: Compared to the major haplotype T-G-T-C-T-A, the relative fluorescence intensities of haplotypes C-A-T-C-T-A, C-G-T-C-T-A, C-G-C-A-G-T, and C-G-T-A-T-A were significantly lower, and that of haplotype C-G-C-A-G-A was significantly higher. Furthermore, the effects of the rs4140535T allele, the rs17273700C-rs11568817G linkage combination, and the rs1228814A allele made their relative fluorescence intensities significantly higher than their counterparts at each locus. Conversely, the rs1778258A and rs130058T alleles decreased the relative fluorescence intensities. In addition, we found that regions from - 1587 to - 1371 bp (TSS, + 1), - 1149 to - 894 bp, - 39 to + 130 bp, + 130 to + 341 bp, and + 341 to + 505 bp upregulated gene expression. In contrast, regions - 603 to - 316 bp and + 130 to + 341 bp downregulated gene expression. Region + 341 to + 505 bp played a decisive role in gene transcription. CONCLUSIONS: HTR1B 5' regulatory region polymorphisms have regulatory effects on gene expression and potential correlate with several pathology and physiology conditions. This study suggests that a crucial sequence for transcription is located in region + 341 ~ + 505 bp. Regions - 1587 to - 1371 bp, - 1149 to - 894 bp, - 603 to - 316 bp, - 39 to + 130 bp, and + 130 to + 341 bp contain functional sequences that can promote or suppress the HTR1B gene expression.

Genetic characterization of 15 autosomal STRs in the interior Sindhi population of Pakistan and their phylogenetic relationship with other populations.

Genetic structure of a population can be influenced by evolutionary processes and cultural histories which can alter the frequencies of different variants at particular genetic markers. These characteristics make DNA evidence suitable for forensic applications. Little relevant data are available from the interior Sindhi population; thus, in the current study, we have investigated 15 autosomal STRs in 181 unrelated individuals belonging to the interior parts of Sindh Pakistan, to establish its lineage and parameters of forensic interest. These STRs revealed a high power of discrimination (CPD), power of exclusion (CPE) and matching probability (CMP) are 0.9999999999999999968997, 0.99998612 and 3.1003 × 10-18 respectively. The genetic distances, neighbour-joining (NJ) tree, interactivity test and principal component analysis (PCA) based on 15 autosomal STR loci showed that the interior Sindhi population had a closer genetic relationship with Pakistani populations and distant relationships with regional (India and Afghanistan) populations. The present findings exhibited that STRs included in AmpFLSTR Identifiler kit (Applied Biosystems) are genetically polymorphic in the interior Sindhi population of Pakistan. This study provides valuable population genetic data for the genetic information study, forensic human individual identification and paternity testing.

Genetic structure and forensic characteristics of the Korean population revealed by GoldenEye 20A.

BACKGROUND: In China, most Koreans live in the Northeast, including Jilin (59.64%), Heilongjiang (20.21%), and Liaoning (12.55%) provinces, while the rest are spread to other parts of China. Koreans across China share a common culture, which is similar to Korea. AIM: The Combined DNA Index System or CODIS has been increased from thirteen to twenty loci, so it is important to generate improved profiles with the help of these additional loci. SUBJECTS AND METHODS: In the current study we have analysed 564 unrelated individuals from the Yanbian Korean population using the GoldenEyeTM 20 A kit (Beijing PeopleSpot Inc). Allelic frequencies, population comparisons and forensic statistical parameters of commonly used short tandem repeats were calculated for the Yanbian Korean population from Jilin province, P.R. China. RESULTS: A total of 232 alleles were observed and all the loci were found to be in Hardy-Weinberg equilibrium after Bonferroni correction. The combined power of discrimination was 99. 999999999999999999999913% and the combined power of exclusion was 0.999999995349261. CONCLUSION: Phylogenetic parameters showed that the Yanbian Koreans living in Jilin had the closest genetic relationship with South Koreans and other East Asian populations. The present study provides a precise reference database of Jilin Koreans for forensic applications and studies of population genetics.

Population genetics of 19 Y-STR loci in Yanbian Korean samples from China.

BACKGROUND: China harbors 56 ethnic groups, including Korean, with a population size of approximately 1.92 million at the 2010 census. Most of the Koreans live in Northeastern parts of China, including Jilin (59.64%), Heilongjiang (20.21%), and Liaoning (12.55%) provinces, and the rest are spread to other parts of China. Koreans across China share a common culture, which is similar to Korea. METHODS: We have explored the genetic characteristics of 20 Y-chromosomal short tandem repeat (Y-STR) loci in 252 unrelated Chinese Korean male individuals from Jilin Province, using a Goldeneye 20Y amplification kit. Moreover, phylogenetic analysis was performed between the Korean population and other relevant populations based on the Y-STR haplotypes. RESULTS: We have found 237 different haplotypes among 252 unrelated individuals. The haplotype frequencies ranged from 0.0238 to 0.0040, while gene diversity ranged from 0.9666 (DYS385a/b) to 0.2260 (DYS391). The random match probability was 0.0048, the haplotype diversity was 0.9992 ± 0.0006 and discrimination capacity was 0.9405. Population comparison revealed that Korean populations are lining up together with other Korean populations from East Asia. CONCLUSION: Our results showed that the 20 Y-STR loci in the Yanbian Korean population are valuable for forensic application and human genetics. The Yanbian Koreans have lined up with other Korean population from China and Korea while showing significant differences from other East Asian populations.

Association between polymorphisms in the GRIN1 gene 5' regulatory region and schizophrenia in a northern Han Chinese population and haplotype effects on protein expression in vitro.

BACKGROUND: Schizophrenia is a severe neurodevelopmental disorder with a complex genetic and environmental etiology. Abnormal glutamate ionotropic N-methyl-D-aspartate receptor (NMDA) type subunit 1 (NR1) may be a potential cause of schizophrenia. METHODS: We conducted a case-control study to investigate the association between the GRIN1 gene, which encodes the NR1 subunit, and the risk of schizophrenia in a northern Chinese Han population using Sanger DNA sequencing. The dual luciferase reporter assay was used to detect the influence of two different haplotypes on GRIN1 gene expression. RESULTS: Seven SNPs (single nucleotide polymorphisms), including rs112421622 (- 2019 T/C), rs138961287 (- 1962--1961insT), rs117783907 (-1945G/T), rs181682830 (-1934G/A), rs7032504 (-1742C/T), rs144123109 (-1140G/A), and rs11146020 (-855G/C) were detected in the study population. Rs117783907 (-1945G/T) was associated with the occurrence of schizophrenia as a protective factor. The genotype frequencies of rs138961287 (- 1962--1961insT) and rs11146020 (-855G/C) were statistically different between cases and controls (p < 0.0083). The other four variations were not shown to be associated with the disease. Two haplotypes were composed of the seven SNPs, and distribution of T-del-G-G-C-G-G was significantly different between the case and control groups. However, the dual luciferase reporter assay showed that neither of the haplotypes affected luciferase expression in HEK-293 and SK-N-SH cell lines. CONCLUSIONS: The GRIN1 gene may be related to the occurrence of schizophrenia. Additional research will be needed to fully ascertain the role of GRIN1 in the etiology of schizophrenia.

Analysis and interpretation of mixture DNA using AS-PCR of mtDNA.

Semi-nested PCR with allele-specific (AS) primers and sequencing of mitochondrial DNA (mtDNA) were performed to analyze and interpret DNA mixtures, especially when biological materials were degraded or contained a limited amount of DNA. SNP-STR markers were available to identify the minor DNA component using AS-PCR; moreover, SNPs in mtDNA could be used when the degraded or limited amounts of DNA mixtures were not successful with SNP-STR markers. Five pairs of allele-specific primers were designed based on three SNPs (G15043A, T16362C, and T16519C). The sequence of mtDNA control region of minor components was obtained using AS-PCR and sequencing. Sequences of the amplification fragments were aligned and compared with the sequences of known suspects or databases. When this assay was used with the T16362C and T16519C SNPs, we found it to be highly sensitive for detecting small amounts of DNA (∼30 pg) and analyzing DNA mixtures of two contributors, even at an approximately 1‰ ratio of minor and major components. An exception was tests based on the SNP G15043A, which required approximately 300 pg of a 1% DNA mixture. In simulated three contributor DNA mixtures (at rate of 1:1:1), control region fragments from each contributor were detected and interpreted. AS-PCR combined with semi-nested PCR was successfully used to identify the mtDNA control region of each contributor, providing biological evidence for excluding suspects in forensic cases, especially when biological materials were degraded or had a limited amount of DNA.

Polymorphisms in the human serotonin receptor 1B (HTR1B) gene are associated with schizophrenia: a case control study.

BACKGROUND: Schizophrenia is associated with multiple neurotransmitter disorders, including serotonin (5-hydroxytryptamine, 5-HT). The neuromodulatory action of serotonin on brain function largely depends on the action of specific subtypes of serotonin receptors. The serotonin receptor 1B (HTR1B) gene has been proposed to play putative roles in the development of multiple emotional and psychiatric disorders. METHODS: To study the relationship of HTR1B polymorphisms and schizophrenia, gene information was drawn from a cohort of 310 schizophrenic patients (152 men and 158 women) and 313 healthy controls (153 men and 160 women) of northern Han Chinese descent. The χ2 test was used to compare allele and genotype distributions between case and control groups. The haplotype and linkage equilibrium were also assessed in two group comparisons. RESULTS: We detected 14 SNPs. Male patients were observed to have higher frequencies of the A-allele and AA+AG genotype at rs1778258 than female patients (p = 0.012 and p = 0.015, respectively). Both the A-allele and AA+AG genotype were associated with schizophrenia risk (OR = 1.986 and OR = 2.061, respectively), although the statistical significance of the genotype was lost after Bonferroni correction. Linkage analysis showed that rs17273700, rs11568817, rs9361234 and rs58138557 polymorphisms exhibit strong linkage disequilibrium (LD). In addition, schizophrenic patients show stronger linkage between 11,568,817 and rs130058 than healthy controls. CONCLUSIONS: HTR1B polymorphisms are associated with schizophrenia in the northern Han Chinese population, which provides an etiological reference for schizophrenia.

Association of histone modification with the development of schizophrenia.

Schizophrenia, influenced by genetic and environmental factors, may involve epigenetic alterations, notably histone modifications, in its pathogenesis. This review summarizes various histone modifications including acetylation, methylation, phosphorylation, ubiquitination, serotonylation, lactylation, palmitoylation, and dopaminylation, and their implications in schizophrenia. Current research predominantly focuses on histone acetylation and methylation, though other modifications also play significant roles. These modifications are crucial in regulating transcription through chromatin remodeling, which is vital for understanding schizophrenia's development. For instance, histone acetylation enhances transcriptional efficiency by loosening chromatin, while increased histone methyltransferase activity on H3K9 and altered histone phosphorylation, which reduces DNA affinity and destabilizes chromatin structure, are significant markers of schizophrenia.

[Genetic polymorphisms of SNP loci in the 5' and 3' region of TPH2 gene in Northern Chinese Han population].

OBJECTIVE: To investigate the genetic polymorphism in the 5' and 3' region of TPH2 gene of Northern Chinese Han population and to explore its application value in forensic medicine. METHODS: The sequence variants and the genetic polymorphisms of 6 SNP loci (rs4570625, rs11178997, rs11178998, rs41317118, rs17110747 and rs41317114) within a 905 bp 5' flanking region and a 1,104bp 3' flanking region of TPH2 gene were analyzed by DNA sequencing in a total of 244 unrelated healthy individuals in Northern Chinese Han population. The statistical analysis was carried out by Haploview v4.2 software. RESULTS: The genotypic distributions of the 6 SNP loci in the TPH2 gene were in accordance with Hardy-Weinberg equilibrium. One C/T variant in 92922 site was found. There was a high linkage disequilibrium among the 3 SNP loci (rs4570625, rs11178997 and rs11178998) in the 5' region and the 3 SNP loci (rs41317118, rs17110747 and rs41317114) in the 3' region of TPH2 gene, respectively. The parameters of population genetics of 6 SNP loci were obtained. CONCLUSION: There are great polymorphisms in the 5' and 3' region of TPH2 gene in Northern Chinese Han population, which could be used as genetic indexes for association analysis of the related diseases, as well as for forensic individual identification and paternity testing.

[Correlation between genetic polymorphisms of -855 G/C and -1140 G/A in GRIN1 gene and paranoid schizophrenia].

OBJECTIVE: To investigate the single nucleotide polymorphisms (SNP) of -855 G/C and -1140 G/A in promoter regions of GRIN1 gene and find their genetic correlation to paranoid schizophrenia as well as their applicable values in forensic medicine. METHODS: The genetic polymorphisms of -855 G/C and -1140 G/A at the 5' end of GRIN1 gene were detected by PCR restriction fragment length polymorphism and PAGE in 183 healthy unrelated individuals of northern Chinese Han population and 172 patients of paranoid schizophrenia, respectively. The chi2 test was used to identify Hardy-Weinberg equilibrium of the genotype distribution. The differences of genotypes and allelic frequency distributions were compared between the two groups. RESULTS: Distributions of the genotypic frequencies satisfied Hardy-Weinberg equilibrium in both groups. The difference of genotypes was statistically significant between female patient group and female control group in -855 G/C distribution (P < 0.05). The differences of genotypes and allelic frequencies were statistically significant not only between the patient group and the control group but also between female patient group and female control group in -1140 G/A distribution (P < 0.05). CONCLUSION: The SNP of -1140 G/A in promoter regions of GRIN1 gene might positively correlate to paranoid schizophrenia. The genetic factor of schizophrenia is involved in gender tendency. And it could be useful in forensic identification of schizophrenia.

[Influences of cycle index and volume on sensitivity of DNA detection].

OBJECTIVE: To explore the feasibility of improving the sensitivity of DNA detection by increasing the PCR cycle index and decreasing the volume of amplifying system. METHODS: The DNA of semen were collected from 10 healthy irrelevant volunteers, and were quantified to 50, 40, 30, 25, 20, 15, 10 pg/microL, separately. All samples were then amplified in 10, 5, 3 microL volume and at 28, 30, 32, 34, 36 cycles, respectively. 3130 genetic analyzer was used to detect 15 autosomal STR loci. RESULTS: Under the situation of 28 cycles and 3 microL volume, samples which achieved > 40 pg/microL could be correctly typed. Under the situation of 10, 5, 3 microL volume, samples which achieved > 20 pg/microL could be correctly typed at 34 cycles. When increasing the index to 36 cycles, they could not be correctly typed because of the non-specific band. CONCLUSION: DNA detecting sensitivity can be improved to a certain extent by increasing the cycle index and decreasing the volume of amplifying system.

[Genetic polymorphisms of four SNP loci in D5 gene of dopamine receptor in Northern Chinese Han population].

OBJECTIVE: To reveal the genetic polymorphisms of four SNP loci (rs77434921, rs2076907, rs6283, rs1800762) in D5 gene of dopamine receptor (DRD5) in Northern Chinese Han population. METHODS: Four SNP loci of the DRD5 gene of 206 unrelated individuals in Northern Chinese Han population were separately amplified and sequenced by PCR technique and statistically analyzed by Haploview v4.1 software. RESULTS: In Northern Chinese Han population, the genotype frequency distribution of rs77434921, rs2076907, rs6283 and rs1800762 loci in the DRD5 gene were all in accordance with Hardy-Weinberg equilibrium. DP value was 0.145, 0.532, 0.602 and 0.159, while PE value was 0.004, 0.079, 0.196 and 0.007. A linkage disequilibrium among these four SNP loci was also demonstrated, which might infer five haplotypes. CONCLUSION: rs2076907 and rs6283 loci of DRD5 gene in the Northern Chinese Han population have high genetic polymorphisms, which can be useful for forensic identification of individuals.

[Polymorphisms of rs4906902 and rs8179184 loci in the promoter of the GABRB3 gene and their relevance with schizophrenia].

OBJECTIVE: To investigate the polymorphisms of rs4906902 and rs8179184 loci in the promoter of the gamma-aminobutyric acid(GABA) receptor A, beta3 subunit gene (GABRB3), and their relevance with schizophrenia. METHODS: PCR and DNA sequencing were used to detect the polymorphisms of rs4906902 and rs8179184 loci in 210 healthy individuals (control group) and 206 schizophrenic patients (case group) of the Han population in northern China. The chi2 test was used to identify Hardy-Weinberg equilibrium of the genotype distribution in the control group followed by comparing differences in genotype and haplotype frequency distributions between two groups. RESULTS: Distributions of the genotype frequencies fit the law of Hardy-Weinberg equilibrium in the control group. rs4906902 and rs8179184 loci were in linkage disequilibrium and showed two haplotypes which were T-G and C-A. The differences of genotypic frequencies and haplotype frequencies were statistically significant between the two groups (P < 0.05). The frequency of haplotype C-A in the case group was significantly higher than in the control group. Genotypic and haplotype frequencies in the maternal line and paternal line were statistically significant in the case group (P < 0.05). CONCLUSION: The haplotype of C-A in rs4906902 and rs8179184 loci in the promoter of GABRB3 gene may be maternally inherited and positively associated with schizophrenia and may be a useful tool in the forensic identification of schizophrenia.

[Relationship between genetic polymorphisms of 3 SNP loci in 5-HTT gene and paranoid schizophrenia].

OBJECTIVE: To investigate the population genetic data of 3 SNP loci (rs25533, rs34388196 and rs1042173) of 5-hydroxytryptamine transporter (5-HTT) gene and the association with paranoid schizophrenia. METHODS: Three SNP loci of 5-HTT gene were examined in 132 paranoid schizophrenia patients and 150 unrelated healthy individuals of Northern Chinese Han population by PCR-RFLP technique. The Hardy-Weinberg equilibrium test was performed using the chi-square test and the data of haplotype frequency and population genetics parameters were statistically analyzed. RESULTS: Among these three SNP loci, four haplotypes were obtained. There were no statistically significant differences between the patient group and the control group (P > 0.05). The DP values of the 3 SNP loci were 0.276, 0.502 and 0.502. The PIC of them were 0.151, 0.281 and 0.281. The PE of them were 0.014, 0.072 and 0.072. CONCLUSION: The three SNP loci and four haplotypes of 5-HTT gene have no association with paranoid schizophrenia, while the polymorphism still have high potential application in forensic practice.

Corrigendum: The heart of silk road "Xinjiang", its genetic portray, and forensic parameters inferred from autosomal STRs.

[This corrects the article DOI: 10.3389/fgene.2021.760760.].

The effect of human GRIN1 gene 5' functional region on gene expression regulation in vitro.

INTRODUCTION: Abnormal expression of ionotropic glutamate receptor NMDA type subunit 1, the key subunit of the NMDA receptor, may be related to many neuropsychiatric disorders. In this study, we explored the functional sequence of the 5' regulatory region of the human GRIN1 gene and discussed the transcription factors that may regulate gene expression. MATERIALS AND METHODS: Twelve recombinant pGL3 vectors with gradually truncated fragment lengths were constructed, transfected into HEK-293, U87, and SK-N-SH cell lines, and analyzed through the luciferase reporter gene assay. JASPAR database is used to predict transcription factors. RESULTS: In SK-N-SH and U87 cell lines, regions from -337 to -159 bp, -704 to -556 bp inhibited gene expression, while -556 to -337 bp upregulated gene expression. In HEK-293 and U87 cell lines, the expression of fragment -1703 to + 188 bp was significantly increased compared to adjacent fragments -1539 to + 188 bp and -1843 to + 188 bp. The protein expressions of fragments -2162 to + 188 bp and -2025 to + 188 bp, -1539 to + 188 bp and -1215 to + 188 bp, -1215 to + 188 bp and -1066 to + 188 bp were significantly different in HEK-293 and SK-N-SH cells. According to the predictions of the JASPAR database, the transcription factors REST, EGR1, and CREB1/HIC2 may bind the DNA sequences of GRIN1 gene from the -337 to -159, -556 to -337, and -704 to -556, respectively. In addition, zinc finger transcription factors may regulate the expression of other differentially expressed fragments. CONCLUSIONS: Abnormal transcription regulation in the proximal promoter region of GRIN1 (-704 to + 188 bp) may be involved in the course of neuropsychiatric diseases.

PADI1 and Its Co-Expressed Gene Signature Unveil Colorectal Cancer Prognosis and Immunotherapy Efficacy.

Peptidyl arginine deiminase 1 (PADI1) catalyzes protein citrullination and has a role in regulating immune responses. The tumor immune microenvironment has been reported to be important in colorectal cancer (CRC), which was correlated with the ability of CRC patients to benefit from immunotherapy. However, there is a lack of molecular markers for matching CRC immunotherapy. Previously, single-gene risk models have only considered the effect of individual genes on intrinsic tumor properties, ignoring the role of genes and their co-expressed genes as a whole. In this study, we analyzed the differential expression of PADI1 in colorectal cancer (CRC). We found that PADI1 was highly expressed in CRC. Subgroup survival analysis revealed a prognostic survival difference for PADI1 in CRC patients aged less than 65 years, male, T stage, N0, M0, and stage I-II (p < 0.05). In addition, we analyzed the functions and signaling pathways associated with PADI1 in CRC and found that it was highly enriched in several immune-related functions and pathways. Then, a set of PADI1 co-expressed genes (PCGs) risk-prognosis scores was developed with PADI1 as the core, which could accurately predict the prognosis of CRC (p < 0.05). PCGs risk score can be an independent prognostic factor for CRC. A new set of Norman plot models were developed for clinical characteristics with age, sex, and TNM stage, which can accurately predict CRC 1, 3, and 5 years survival, and calibration curves and decision curve analysis (DCA) validated the accuracy of the models. The risk score assessed the immune microenvironment of CRC and found that the immune score was higher in the low-risk group, and CD4+ T cells, helper T cells, and eosinophils were more infiltrated in the low-risk group (p < 0.05). Immunotherapy efficacy was better in the low-risk group (p < 0.05). The underlying mechanism may be that the high-risk group of PCGs was enriched in some pathways that promote immune escape and immune dysfunction. In conclusion, PCGs may better predict CRC prognosis and immunotherapeutic response.