Biomaterial Database

Comparison of Genomic and Epigenomic Expression in Monozygotic Twins Discordant for Rett Syndrome. 2013

Kunio Miyake, and Chunshu Yang, and Yohei Minakuchi, and Kenta Ohori, and Masaki Soutome, and Takae Hirasawa, and Yasuhiro Kazuki, and Noboru Adachi, and Seiko Suzuki, and Masayuki Itoh, and Yu-Ichi Goto, and Tomoko Andoh, and Hiroshi Kurosawa, and Mitsuo Oshimura, and Masayuki Sasaki, and Atsushi Toyoda, and Takeo Kubota

Department of Epigenetic Medicine, Faculty of Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Japan.

Monozygotic (identical) twins have been widely used in genetic studies to determine the relative contributions of heredity and the environment in human diseases. Discordance in disease manifestation between affected monozygotic twins has been attributed to either environmental factors or different patterns of X chromosome inactivation (XCI). However, recent studies have identified genetic and epigenetic differences between monozygotic twins, thereby challenging the accepted experimental model for distinguishing the effects of nature and nurture. Here, we report the genomic and epigenomic sequences in skin fibroblasts of a discordant monozygotic twin pair with Rett syndrome, an X-linked neurodevelopmental disorder characterized by autistic features, epileptic seizures, gait ataxia and stereotypical hand movements. The twins shared the same de novo mutation in exon 4 of the MECP2 gene (G269AfsX288), which was paternal in origin and occurred during spermatogenesis. The XCI patterns in the twins did not differ in lymphocytes, skin fibroblasts, and hair cells (which originate from ectoderm as does neuronal tissue). No reproducible differences were detected between the twins in single nucleotide polymorphisms (SNPs), insertion-deletion polymorphisms (indels), or copy number variations. Differences in DNA methylation between the twins were detected in fibroblasts in the upstream regions of genes involved in brain function and skeletal tissues such as Mohawk Homeobox (MKX), Brain-type Creatine Kinase (CKB), and FYN Tyrosine Kinase Protooncogene (FYN). The level of methylation in these upstream regions was inversely correlated with the level of gene expression. Thus, differences in DNA methylation patterns likely underlie the discordance in Rett phenotypes between the twins.

UI	MeSH Term	Description	Entries
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004252	DNA Mutational Analysis	Biochemical identification of mutational changes in a nucleotide sequence.	Mutational Analysis, DNA,Analysis, DNA Mutational,Analyses, DNA Mutational,DNA Mutational Analyses,Mutational Analyses, DNA
D005091	Exons	The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.	Mini-Exon,Exon,Mini Exon,Mini-Exons
D005838	Genotype	The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.	Genogroup,Genogroups,Genotypes
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014430	Twins, Monozygotic	Two off-spring from the same PREGNANCY. They are from a single fertilized OVUM that split into two EMBRYOS. Such twins are usually genetically identical and of the same sex.	Twins, Identical,Identical Twin,Identical Twins,Monozygotic Twin,Monozygotic Twins,Twin, Identical,Twin, Monozygotic
D015518	Rett Syndrome	An inherited neurological developmental disorder that is associated with X-LINKED INHERITANCE and may be lethal in utero to hemizygous males. The affected female is normal until the age of 6-25 months when progressive loss of voluntary control of hand movements and communication skills; ATAXIA; SEIZURES; autistic behavior; intermittent HYPERVENTILATION; and HYPERAMMONEMIA appear. (From Menkes, Textbook of Child Neurology, 5th ed, p199)	Autism-Dementia-Ataxia-Loss of Purposeful Hand Use Syndrome,Cerebroatrophic Hyperammonemia,Autism, Dementia, Ataxia, and Loss of Purposeful Hand Use,Rett Disorder,Rett's Disorder,Rett's Syndrome,Autism Dementia Ataxia Loss of Purposeful Hand Use Syndrome,Cerebroatrophic Hyperammonemias,Hyperammonemia, Cerebroatrophic,Hyperammonemias, Cerebroatrophic,Retts Syndrome,Syndrome, Rett,Syndrome, Rett's
D015894	Genome, Human	The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.	Human Genome,Genomes, Human,Human Genomes
D044127	Epigenesis, Genetic	A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.	Epigenetic Processes,Epigenetic Process,Epigenetics Processes,Genetic Epigenesis,Process, Epigenetic,Processes, Epigenetic,Processes, Epigenetics