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Schizophrenia (SZ) is a severe, complex, and common mental disorder with high heritability (80%), an adult age of onset, and high discordance (∼50%) in monozygotic twins (MZ). Extensive studies on familial and non-familial cases have implicated a number of segregating mutations and de novo changes in SZ that may include changes to the mitochondrial genome. Yet, no single universally causal variant has been identified, highlighting its extensive genetic heterogeneity. This report specifically focuses on the assessment of changes in the mitochondrial genome in a unique set of monozygotic twins discordant (MZD) for SZ using blood. Genomic DNA from six pairs of MZD twins and two sets of parents ( = 16) was hybridized to the Affymetrix Human SNP Array 6.0 to assess mitochondrial DNA copy number (mtDNA-CN). Whole genome sequencing (WGS) and quantitative polymerase chain reaction (qPCR) was performed for a subset of MZD pairs and their parents and was also used to derive mtDNA-CN estimates. The WGS data were further analyzed to generate heteroplasmy (HP) estimates. Our results show that mtDNA-CN estimates for within-pair and mother-child differences were smaller than comparisons involving unrelated individuals, as expected. MZD twins showed discordance in mtDNA-CN estimates and displayed concordance in directionality of differences for mtDNA-CN across all technologies. Further, qPCR performed better than Affymetrix in estimating mtDNA-CN based on relatedness. No reliable differences in HP were detected between MZD twins. The within-MZD differences in mtDNA-CN observed represent postzygotic somatic changes that may contribute to discordance of MZ twins for diseases, including SZ.
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http://dx.doi.org/10.1017/thg.2023.34 | DOI Listing |
Twin Res Hum Genet
August 2024
Department of Psychology, California State University, Fullerton, California, USA.
A tribute to the life and career of Dr Milton Diamond, a leading figure in twin studies of transsexuality and gender identity, is presented. Dr Diamond is famous for revealing the truth about the unsuccessful effort to change a monozygotic male Canadian twin into a female, following accidental ablation of his penis during circumcision. A short summary of recent twin research on human sexuality and transsexuality, focused on Dr Diamond's contributions, is then presented.
View Article and Find Full Text PDFEur J Orthod
December 2024
Adelaide Dental School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5000, Australia.
Objectives: This study aimed to determine the genetic and environmental contributions to phenotypic variations of palatal morphology during development.
Methods: Longitudinal three-dimensional digital maxillary dental casts of 228 twin pairs (104 monozygotic and 124 dizygotic) at primary, mixed, and permanent dentition stages were included in this study. Landmarks were placed on the casts along the midpoints of the dento-gingival junction on the palatal side of each tooth and the mid-palatine raphe using MeshLab.
Twin Res Hum Genet
December 2024
Department of Psychology, California State University, Fullerton, California, USA.
Dr H. Keith Sigmundson co-authored a seminal article (with the late Dr Milton Diamond) that revealed the truth about a highly controversial twin case. Specifically, the genitals of an infant male monozygotic twin were accidentally destroyed during a medical procedure performed to alleviate his difficult urination.
View Article and Find Full Text PDFClin Transl Med
December 2024
Department of Obstetrics, Center of Fetal Medicine & intrauterine pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Dear Editor, in this study, we propose a novel linkage disequilibrium information-based noninvasive zygosity (LDNZ) assessment method in twin pregnancies. It combines fetus-specific allele frequency analysis with LD block to reduce the number of required single nucleotide polymorphism markers and experiment costs. LDNZ method offers a noninvasive, accurate, and cost-effective solution for zygosity assessment, addressing the need for precise obstetric care in twin pregnancies.
View Article and Find Full Text PDFAnn Neurol
December 2024
Department of Neurology, Faculty of Medicine, Juntendo University, Tokyo, Japan.
Objective: Variants in PRKN and PINK1 are the leading cause of early-onset autosomal recessive Parkinson's disease, yet many cases remain genetically unresolved. We previously identified a 7 megabases complex structural variant in a pair of monozygotic twins using Oxford Nanopore Technologies (ONT) long-read sequencing. This study aims to determine if ONT long-read sequencing can detect a second variant in other unresolved early-onset Parkinson's disease (EOPD) cases with 1 heterozygous PRKN or PINK1 variant.
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