with live links removed OT: Phenotypic differences in genetically identical organisms: the epigenetic perspective

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1: http://hmg.oxfordjournals.org/cgi/reprint/14/suppl_1/R11

Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R11-8.

Phenotypic differences in genetically identical organisms: the

epigenetic perspective.

Wong AH, Gottesman II, Petronis A.

The Centre for Addiction and Mental Health, Department of

Psychiatry, Toronto, Ontario, Canada.

Human monozygotic twins and other genetically identical organisms

are almost always strikingly similar in appearance, yet they are often

discordant for important phenotypes including complex diseases. Such

variation among organisms with virtually identical chromosomal DNA

sequences has largely been attributed to the effects of environment.

Environmental factors can have a strong effect on some phenotypes, but

evidence from both animal and human experiments suggests that the impact

of environment has been overstated and that our views on the causes of

phenotypic differences in genetically identical organisms require

revision. New theoretical and experimental opportunities arise if

epigenetic factors are considered as part of the molecular control of

phenotype. Epigenetic mechanisms may explain paradoxical findings in

twin and inbred animal studies when phenotypic differences occur in the

absence of observable environmental differences and also when

environmental differences do not significantly increase the degree of

phenotypic variation.

PMID: 15809262

2: http://schizophreniabulletin.oxfordjournals.org/cgi/reprint/29/1/169

Schizophr Bull. 2003;29(1):169-78.

Monozygotic twins exhibit numerous epigenetic differences: clues to

twin discordance?

Petronis A, Gottesman II, Kan P, Kennedy JL, Basile VS, Paterson AD,

Popendikyte V.

The Krembil Family Epigenetics Laboratory, Centre for Addiction and

Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 Canada.

arturas_petronis@...

The goal of this pilot study was to explore the putative molecular

mechanisms underlying the phenotypic discordance of monozygotic (MZ)

twins. Thus, patterns of epigenetic DNA modification were investigated

in the 5'-regulatory region of the dopamine D2 receptor gene (DRD2) in

two pairs of monozygotic twins, one concordant and one discordant for

schizophrenia. The bisulfite DNA modification-based approach was used to

fine-map methylated cytosines in DRD2 in genomic DNA extracted from

lymphocytes. Numerous DNA methylation differences were identified in the

analyzed region both within and between the pairs of MZ twins.

" Epigenetic distances " between MZ twins were calculated and used for the

comparison of twin DRD2 methylation profiles. It was detected that the

affected twin from the pair discordant for schizophrenia was

epigenetically " closer " to the affected concordant twins than to his

unaffected MZ co-twin. Although the epigenetic analysis was conducted

for only several hundred base pairs of DRD2, the fact that numerous

studies identified nonuniform methylation patterns across the clones of

bisulfite-modified DNA from the same individual, as well as nonuniform

patterns across different individuals, argues for the universality of

intra- and interindividual epigenetic variation. Epigenetic studies

should provide insight into the molecular causes of differential

susceptibility to a disease in genetically identical organisms that may

generalize to singletons.

PMID: 12908672

3: http://ajp.psychiatryonline.org/cgi/content/full/155/3/422

Am J Psychiatry. 1998 Mar;155(3):422-4. Links

Genomic discordance between monozygotic twins discordant for

schizophrenia.

Tsujita T, Niikawa N, Yamashita H, Imamura A, Hamada A, Nakane Y,

Okazaki Y.

Department of Human Genetics, Nagasaki University School of

Medicine, Japan. f0932@...

OBJECTIVE: Genomic DNA of monozygotic twins discordant for

schizophrenia was analyzed to determine whether their genomes were truly

identical. METHOD: The subjects were monozygotic male twins, one of whom

had DSM-III-R schizophrenia, undifferentiated type. Genomic DNA was

extracted from leukocytes and was applied to restriction landmark genome

scanning analysis, which was developed for a high-speed survey of

restriction sites throughout a genome and measurement of their copy

number in each locus. RESULTS: After comparisons of patterns with

approximately 2,000 spots, the authors detected at least two spots with

autoradiographic intensities that obviously differed in the two twins.

CONCLUSIONS: The discrepancies likely were generated either by

differences in the methylation status at NotI sites between the twins or

by submicroscopic changes occurring at NotI-flanking sites in one twin

after (or simultaneous with) twinning. In either case, the difference

may influence the transcription level of one or more genes.

PMID: 9501757