RESUMEN
Improving accuracy of the available predictive DNA methods is important for their wider use in routine forensic work. Information on age in the process of identification of an unknown individual may provide important hints that can speed up the process of investigation. DNA methylation markers have been demonstrated to provide accurate age estimation in forensics, but there is growing evidence that DNA methylation can be modified by various factors including diseases. We analyzed DNA methylation profile in five markers from five different genes (ELOVL2, C1orf132, KLF14, FHL2, and TRIM59) used for forensic age prediction in three groups of individuals with diagnosed medical conditions. The obtained results showed that the selected age-related CpG sites have unchanged age prediction capacity in the group of late onset Alzheimer's disease patients. Aberrant hypermethylation and decreased prediction accuracy were found for TRIM59 and KLF14 markers in the group of early onset Alzheimer's disease suggesting accelerated aging of patients. In the Graves' disease patients, altered DNA methylation profile and modified age prediction accuracy were noted for TRIM59 and FHL2 with aberrant hypermethylation observed for the former and aberrant hypomethylation for the latter. Our work emphasizes high utility of the ELOVL2 and C1orf132 markers for prediction of chronological age in forensics by showing unchanged prediction accuracy in individuals affected by three diseases. The study also demonstrates that artificial neural networks could be a convenient alternative for the forensic predictive DNA analyses.
Asunto(s)
Acetiltransferasas/genética , Envejecimiento/genética , Enfermedad de Alzheimer/genética , Metilación de ADN , Enfermedad de Graves/genética , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , Preescolar , Islas de CpG/genética , Elongasas de Ácidos Grasos , Femenino , Genética Forense , Marcadores Genéticos , Humanos , Péptidos y Proteínas de Señalización Intracelular , Factores de Transcripción de Tipo Kruppel , Proteínas con Homeodominio LIM/genética , Masculino , Proteínas de la Membrana/genética , Metaloproteínas/genética , Persona de Mediana Edad , Análisis Multivariante , Proteínas Musculares/genética , Redes Neurales de la Computación , Factores de Transcripción Sp/genética , Factores de Transcripción/genética , Proteínas de Motivos Tripartitos , Adulto JovenRESUMEN
Individual age estimation can be applied to criminal, legal, and anthropological investigations. DNA methylation has been established as the biomarker of choice for age prediction, since it was observed that specific CpG positions in the genome show systematic changes during an individual's lifetime, with progressive increases or decreases in methylation levels. Subsequently, several forensic age prediction models have been reported, providing average age prediction error ranges of ±3-4 years, using a broad spectrum of technologies and underlying statistical analyses. DNA methylation assessment is not categorical but quantitative. Therefore, the detection platform used plays a pivotal role, since quantitative and semi-quantitative technologies could potentially result in differences in detected DNA methylation levels. In the present study, we analyzed as a shared sample pool, 84 blood-based DNA controls ranging from 18 to 99 years old using four different technologies: EpiTYPER®, pyrosequencing, MiSeq, and SNaPshotTM. The DNA methylation levels detected for CpG sites from ELOVL2, FHL2, and MIR29B2 with each system were compared. A restricted three CpG-site age prediction model was rebuilt for each system, as well as for a combination of technologies, based on previous training datasets, and age predictions were calculated accordingly for all the samples detected with the previous technologies. While the DNA methylation patterns and subsequent age predictions from EpiTYPER®, pyrosequencing, and MiSeq systems are largely comparable for the CpG sites studied, SNaPshotTM gives bigger differences reflected in higher predictive errors. However, these differences can be reduced by applying a z-score data transformation.
RESUMEN
This study reports sequence characteristics and population genetic data on a 'new' STR locus HumHUU (D16S3433) located in the non-coding region of chromosome 16q. Based on a population sample of 306 non-related Polish individuals 205 genotypes and 15 alleles with length range of 157-211bp were distinguished. No deviation from HWE was observed. The sequence analysis of each D16S3433 allele revealed a tetranucleotide repeat motif with a basic sequence structure (AAAA)(0-1)(AAAG)(11-22)(AAAAG)(AAAA)(AG)(AAAAAAG). The power of discrimination is 0.9538, showing a high degree of polymorphism. The presented results demonstrate that the D16S3433 is a useful genetic marker for forensic purposes and paternity testing.