RESUMO
DNA methylation-based clocks provide the most accurate age estimates with practical implications for clinical and forensic genetics. However, the effects of external factors that may influence the estimates are poorly studied. Here, we evaluated the effect of alcohol consumption on epigenetic age prediction in a cohort of extreme alcohol abusers. Blood samples from deceased alcohol abusers and age- and sex-matched controls were analyzed using the VISAGE enhanced tool for age prediction from somatic tissues that enables examination of 44 CpGs within eight age markers. Significantly altered DNA methylation was recorded for alcohol abusers in MIR29B2CHG. This resulted in a mean predicted age of 1.4 years higher compared to the controls and this trend increased in older individuals. The association of alcohol abuse with epigenetic age acceleration, as determined by the prediction analysis performed based on MIR29B2CHG, was small but significant (ß = 0.190; P-value = 0.007). However, the observed alteration in DNA methylation of MIR29B2CHG had a non-significant effect on age estimation with the VISAGE age prediction model. The mean absolute error in the alcohol-abusing cohort was 3.1 years, compared to 3.3 years in the control group. At the same time, upregulation of MIR29B2CHG expression may have a biological function, which merits further studies.
Assuntos
Alcoolismo , Idoso , Envelhecimento/genética , Alcoolismo/genética , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Epigenômica/métodos , Humanos , LactenteRESUMO
Advances in forensic identification using molecular genetics are helpful in resolving some historical mysteries. The aim of this study was to confirm the authenticity of shrunken-head artifacts exhibited by two Polish museums. Shrunken heads, known as tsantsas, were headhunting trophies of South American Indians (Jivaroan). A special preparation preserved their hair and facial appearance. However, it was quite common to offer counterfeit shrunken heads of sloths or monkeys to collectors of curiosities. We sampled small skin specimens of four shrunken-head skin from the museum collection from Warsaw and Krakow, Poland. Following genomic DNA isolation, highly polymorphic short tandem repeats were genotyped using a commercial chemistry and DNA sequencing analyzer. Haplogroups of human Y chromosome were identified. We obtained an informative genetic profile of genomic short tandem repeats from all the samples of shrunken heads. Moreover, amplification of amelogenin loci allowed for sex determination. All four studied shrunken heads were of human origin. In two ones, a shared Y-chromosome haplogroup Q characteristic for Indigenous Americans was detected. Another artifact was counterfeited because Y-chromosome haplogroup I2 was found, characteristic for the Southeastern European origin. Commercial genetic methods of identification can be applied successfully in studies on the origin and authenticity of some unusual collection items.
Assuntos
Impressões Digitais de DNA , Indígenas Sul-Americanos/genética , Repetições de Microssatélites , Amelogenina/genética , Cromossomos Humanos Y , Genótipo , Cabelo/ultraestrutura , Haplótipos , História do Século XIX , Humanos , Indígenas Sul-Americanos/história , Masculino , Museus , Polônia , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo ÚnicoRESUMO
DNA methylation is known as a biomarker for age with applications in forensics. Here we describe the VISAGE (VISible Attributes through GEnomics) Consortium's enhanced tool for epigenetic age estimation in somatic tissues. The tool is based on eight DNA methylation markers (44 CpGs), bisulfite multiplex PCR followed by sequencing on the MiSeq FGx platform, and three statistical prediction models for blood, buccal cells and bones. The model for blood is based on six CpGs from ELOVL2, MIR29B2CHG, KLF14, FHL2, TRIM59 and PDE4C, and predicts age with a mean absolute error (MAE) of 3.2 years, while the model for buccal cells includes five CpGs from PDE4C, MIR29B2CHG, ELOVL2, KLF14 and EDARADD and predicts age with MAE of 3.7 years, and the model for bones has six CpGs from ELOVL2, KLF14, PDE4C and ASPA and predicts age with MAE of 3.4 years. The VISAGE enhanced tool for age estimation in somatic tissues enables reliable collection of DNA methylation data from small amounts of DNA using a sensitive multiplex MPS assay that provides accurate estimation of age in blood, buccal swabs, and bones using the statistical model tailored to each tissue.
Assuntos
Envelhecimento/genética , Ilhas de CpG , Modelos Estatísticos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amidoidrolases/genética , Análise Química do Sangue , Osso e Ossos/química , Criança , Pré-Escolar , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Metilação de DNA , Proteína de Domínio de Morte Associada a Edar/genética , Epigênese Genética , Elongases de Ácidos Graxos/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Fatores de Transcrição Kruppel-Like/genética , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/química , Reação em Cadeia da Polimerase Multiplex , Análise de Sequência de DNA , Adulto JovemRESUMO
In this study, germline mutations were analyzed for 26,040 parent-child allelic transfers among subjects referred to paternity testing and originating from the Slavonic population of the Southern Poland. Mutation rates were estimated for 15 autosomal microsatellite loci: D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA. There were 35 mutation events observed at 11 from 15 analyzed loci. No mutations were found at TH01, D2S1338, D19S433 and TPOX loci. The mutation rate estimate was 0.0019 [0.0012-0.0028 95% CI] for paternal and 0.0004 [0.0002-0.0009] for maternal meiosis, while 25% mutations remained unassigned. The locus-specific mutation rate ranged from 0.0000 [0.0000-0.0014] to 0.0046 [0.0022-0.0087]. Mutations observed in male germlines were more frequent than in female germlines.