RESUMO
BACKGROUND: Situated at the crossroads of Asia, Middle East and Europe, Turkey has an ethnically diverse population of over 78 milllion people. AIM: To investigate the population genetics and potential differences in the autosomal short tandem repeat (STR) polymorphisms across all the major geographic regions and largest metropolitan province of Turkey within the context of the Near Eastern/European genetic landscape. SUBJECTS AND METHODS: Samples from a total of 5299 unrelated individuals were analysed at 10 common [D2S1338, D3S1358, D8S1179, D16S539, D18S51, D19S433, D21S11, FGA, TH01, vWA] and five new European Standard Set (ESS) core autosomal STR loci [D1S1656, D2S441, D10S1248, D12S391, D22S1045]. RESULTS: Allele frequencies, statistical parameters of forensic interest and population differentiation tests were calculated for nine population datasets corresponding to the seven major geographic regions, the largest metropolitan province, and a combined dataset for the entire country. Cumulative results confirmed the presence of significant differences among these nine autosomal datasets themselves and with those from the nearby populations, therefore justifying the differential use of these separate datasets on a case-by-case basis in forensic investigations. CONCLUSION: This collection of autosomal STR population datasets comprises the largest and most comprehensive of its kind from Turkey so far.
Assuntos
Frequência do Gene , Repetições de Microssatélites , Polimorfismo Genético , Feminino , Humanos , Masculino , TurquiaRESUMO
Here, we report an incest paternity case involving three biological brothers as alleged fathers (AFs), their biological sister and her child that was investigated using the Investigator ESSplex Plus, AmpFLSTR Identifiler Plus/Investigator IDplex Plus and PowerPlex 16 kits. Initial duo paternity investigations using 15-loci autosomal short tandem repeat (STR) analyses failed to exclude any of the AFs. Despite the fact that one of the brothers, AF1, had a mismatch with the child at a single locus (D2S1338), the possibility of a single-step mutation could not be ruled out. When the number of autosomal STR loci analysed was increased to 22 without the inclusion of the mother, AF2 and AF3 still could not be excluded, since both of them again had no mismatches with the child. A breakthrough was possible only upon inclusion of the mother so that trio paternity investigations were carried out. This time AF1 and AF2 could be excluded at two loci (D2S1338 and D1S1656) and six loci (vWa, D1S1656, D12S391, FGA, PENTA E and PENTA D), respectively, and AF3 was then the only brother who could not be excluded from paternity. Subsequent statistical analyses suggested that AF3 could be the biological father of the child with a combined paternity index >100 billion and a probability of paternity >99.99999999%. These findings consolidate the fact that complex paternity cases such as those involving incest could benefit more from the inclusion of the mother than simply increasing the number of STR loci analysed.
Assuntos
Impressões Digitais de DNA , Incesto , Repetições de Microssatélites , Paternidade , Irmãos , Adolescente , Feminino , Humanos , Masculino , Mutação , Reação em Cadeia da PolimeraseRESUMO
INTRODUCTION: Nonsyndromic cleft palate is a common birth defect (1:700) with a complex etiology involving both genetic and environmental risk factors. Nicotine, a major teratogen present in tobacco products, was shown to cause alterations and delays in the developing fetus. METHODS: To demonstrate the postpartum effects of nicotine on palatal development, we delivered three different doses of nicotine (1.5, 3.0, and 4.5mg/kg/d) and sterile saline (control) into pregnant BALB/c mice throughout their entire pregnancy using subcutaneous micro-osmotic pump. Dams were allowed to deliver (~day 21 of pregnancy) and neonatal assessments (weight, length, nicotine levels) were conducted, and palatal tissues were harvested for morphological and molecular analyses, as well as transcriptional profiling using microarrays. RESULTS: Consistent administration of nicotine caused developmental retardation, still birth, low birth weight, and significant palatal size and shape abnormality and persistent midline epithelial seam in the pups. Through microarray analysis, we detected that 6232 genes were up-regulated and 6310 genes were down-regulated in nicotine-treated groups compared to the control. Moreover, 46% of the cleft palate-causing genes were found to be affected by nicotine exposure. Alterations of a subset of differentially expressed genes were illustrated with hierarchal clustering and a series of formal pathway analyses were performed using the bioinformatics tools. CONCLUSIONS: We concluded that nicotine exposure during pregnancy interferes with normal growth and development of the fetus, as well results in persistent midline epithelial seam with type B and C patterns of palatal fusion. IMPLICATIONS: Although there are several studies analyzing the genetic and environmental causes of palatal deformities, this study primarily shows the morphological and large-scale genomic outcomes of gestational nicotine exposure in neonatal mice palate.The previous version was incorrect. New authors Ali Nawshad, Hasan Otu, Janki Sharma, and Elizabeth Sheldon have been included in this version; the funding and acknowledgement sections have been updated accordingly; the article title, some text, and one supplementary data file have been edited; and the corresponding author has been changed. The original corresponding author regrets these earlier errors.
Assuntos
Fissura Palatina/embriologia , Desenvolvimento Fetal/efeitos dos fármacos , Nicotina/farmacologia , Palato/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Camundongos Endogâmicos BALB C , Modelos Animais , Palato/embriologia , Palato/crescimento & desenvolvimento , Gravidez , Resultado da Gravidez , Fumar/efeitos adversos , NatimortoRESUMO
We scanned suspicious 1200 paternity cases and 650 sexual abuse victims in Council of Forensic Medicine of Turkey between 2011 and 2014 and detected 50 incest cases and evaluated the forensic and genetic data of incest cases for source of DNA evidence, gender, age, SES (Socioeconomic status) and geographic location of victim, abusive person, extent of incest, pregnancy from incest and date of gestation termination and also aimed to discuss some DNA profiling difficulties. We detected incest from DNA evidences of curettage material (34%; Chorionic Villi (12%) and fetal tissue (22%)), alive baby after pregnancy (28%), sperm in vaginal swab (10%), sperm in anal swab (2%), sperm on clothing (24%) and in one case both sperm on clothing and in vaginal swab (2%). It was found that the most common incestuous relationship was elder-brother-sister incest (34%) and the second most common relationship was father-daughter incest (28%). The rarest incest was mother-son incest with only one reported case (2%). Forty-three victims (86%) were younger than 18 years old and 7 victims (14%) were older than 18 years old. Thirty-eight cases described full sexual intercourse and 31 of them culminated in pregnancy and 14 of them gave birth at the end of pregnancy. We had paternity rejection problem 3 (10%) of 31 incest cases between tested genetically related alleged fathers. Totally 20 STR loci did not discriminate the alleged fathers in two cases and we treated this problem increasing the number of STR loci and finally got the discrimination. In one case we detected same triallelic variant pattern at the same D3S1358 STR locus in both tested parents but child had not got STR variant; had only two alleles at this loci. We then evaluated the peak height values of STR variant alleles of tested persons and concluded a tetra-allelic baby without any STR incompatibility of 15 STR loci. Finally, forensic experts should aware of some DNA profiling difficulties while analyzing paternity incest cases due to increasing intra familial allelic share. We suggested that first try increasing the number of compared STR loci and secondly use alternative genetic markers and also be careful while evaluating triallelic STR variants.
Assuntos
Impressões Digitais de DNA , Incesto , Paternidade , Adolescente , Alelos , Canal Anal , Vilosidades Coriônicas/química , Feminino , Humanos , Incesto/estatística & dados numéricos , Masculino , Repetições de Microssatélites , Gravidez , Manejo de Espécimes , Espermatozoides/química , Turquia , VaginaRESUMO
In paternity cases where individuals are close relatives, it may be necessary to evaluate mother's DNA profile (trio test) and to increase the number of polymorphic STR loci that are analyzed. In our case, two alleged fathers who are brothers and the child (duo case) were analyzed based on 20 STR loci; however, no exclusions could be achieved. Then trio test (with mother) was performed using the Identifiler Plus kit (Applied Biosystems) and no exclusions could be achieved again. Analysis performed with the ESS Plex Plus kit (Qiagen), the paternity of one of the two alleged fathers was rejected only on 2 STR loci. We made the calculations of power of exclusion values to interpret our results more properly. The probability of exclusion (PE) is calculated as 0.9776546 in 15 loci of Identifiler Plus kit without mother. The PE is calculated as 0.9942803, if 5 additional loci from ESS Plex Plus kit are typed. The PE becomes 0.9961048 for the Identifiler Plus kit in trio analysis. If both Identifiler Plus and ESS Plex Plus kits are used for testing, the PE is calculated as 0.999431654, which indicates that the combined kits are highly discriminating.
Assuntos
DNA/análise , Repetições de Microssatélites/genética , Paternidade , Irmãos , Criança , DNA/genética , Pai , Feminino , Genética Forense/métodos , Humanos , Masculino , Mães , Polimorfismo Genético , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos TestesRESUMO
Despite the association of several miRNAs with bladder cancer, little is known about the miRNAs' regulatory networks. In this study, we aimed to construct potential networks of bladder-cancer-related miRNAs and their known target genes using miRNA expression profiling and bioinformatics tools and to investigate potential key molecules that might play roles in bladder cancer regulatory networks. Global miRNA expression profiles were obtained using microarray followed by RT-qPCR validation using two randomly selected miRNAs. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of three selected KEGG pathways were visualized by Cytoscape software. We finally gained 19 deregulated miRNAs, including 5 ups- and 14 down regulated in 27 bladder-cancer tissue samples and 8 normal urothelial tissue samples. The enrichment results of deregulated miRNAs and known target genes showed that most pathways were related to cancer or cell signaling pathways. We determined the hub CDK6, BCL2, E2F3, PTEN, MYC, RB, and ERBB3 target genes and hub hsa-let-7c, hsa-miR-195-5p, hsa-miR-141-3p, hsa-miR-26a-5p, hsa-miR-23b-3p, and hsa-miR-125b-5p miRNAs of the constructed networks. These findings provide new insights into the bladder cancer regulatory networks and give us a hypothesis that hsa-let-7c, hsa-miR-195-5p, and hsa-miR-125b-5p, along with CDK4 and CDK6 genes might exist in the same bladder cancer pathway. Particularly, hub miRNAs and genes might be potential biomarkers for bladder cancer clinics.
Assuntos
Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , MicroRNAs/genética , Neoplasias da Bexiga Urinária/genética , Quinase 4 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/genética , Regulação Neoplásica da Expressão Gênica , Estudos de Associação Genética , Humanos , Software , Neoplasias da Bexiga Urinária/patologiaRESUMO
Forensic geneticists often use short tandem repeats (STRs) to solve cases. However, STRs can be insufficient when DNA samples are degraded due to environmental exposure and mass disasters, alleged and real relatives are genetically related in paternity or kinship analyses, or a suspect is lacking. In such cases, single-nucleotide polymorphisms (SNPs) can provide valuable information and thus should be seriously considered as a tool to help resolve challenging cases. In this review, the current status of SNP analyses in forensic applications and the comparative advantages and disadvantages of SNPs with other biomarkers are discussed.