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

[Guest guest]

Here's how the post looks if I include live links (which don't take too

much time for sharing)

A newspaper discussion had me wallowing in PubMed regarding monozygotic

twins discordant for one trait and/or another. Here are some gems.

- - - -

*1: *Hum Mol Genet. <javascript:AL_get(this, 'jour', 'Hum Mol Genet.');>

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

Click here to read

<http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051 & itool=AbstractPlus\

-def & uid=15809262 & db=pubmed & url=http://hmg.oxfordjournals.org/cgi/pmidlookup?vie\

w=long & pmid=15809262>

Phenotypic differences in genetically identical organisms: the

epigenetic perspective.

*Wong AH*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Wong%20AH\

%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RV\

AbstractPlusDrugs1>,

*Gottesman II*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Gottesman\

%20II%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubm\

ed_RVAbstractPlusDrugs1>,

*Petronis A*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Petronis%\

20A%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed\

_RVAbstractPlusDrugs1>.

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: *Schizophr Bull. <javascript:AL_get(this, 'jour', 'Schizophr

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

Click here to read

<http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051 & itool=AbstractPlus\

-def & uid=12908672 & db=pubmed & url=http://schizophreniabulletin.oxfordjournals.org/\

cgi/pmidlookup?view=long & pmid=12908672>

Monozygotic twins exhibit numerous epigenetic differences: clues

to twin discordance?

*Petronis A*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Petronis%\

20A%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed\

_RVAbstractPlusDrugs1>,

*Gottesman II*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Gottesman\

%20II%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubm\

ed_RVAbstractPlusDrugs1>,

*Kan P*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Kan%20P%2\

2%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAb\

stractPlusDrugs1>,

*Kennedy JL*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Kennedy%2\

0JL%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed\

_RVAbstractPlusDrugs1>,

*Basile VS*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Basile%20\

VS%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_\

RVAbstractPlusDrugs1>,

*Paterson AD*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Paterson%\

20AD%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\

d_RVAbstractPlusDrugs1>,

*Popendikyte V*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Popendiky\

te%20V%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pub\

med_RVAbstractPlusDrugs1>.

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: *Am J Psychiatry. <javascript:AL_get(this, 'jour', 'Am J

Psychiatry.');> 1998 Mar;155(3):422-4.Click here to read

<http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051 & itool=AbstractPlus\

-def & uid=9501757 & db=pubmed & url=http://ajp.psychiatryonline.org/cgi/pmidlookup?vi\

ew=long & pmid=9501757>

Links <javascript:PopUpMenu2_Set(Menu9501757);>

Genomic discordance between monozygotic twins discordant for

schizophrenia.

*Tsujita T*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Tsujita%2\

0T%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_\

RVAbstractPlusDrugs1>,

*Niikawa N*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Niikawa%2\

0N%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_\

RVAbstractPlusDrugs1>,

*Yamashita H*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Yamashita\

%20H%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\

d_RVAbstractPlusDrugs1>,

*Imamura A*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Imamura%2\

0A%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_\

RVAbstractPlusDrugs1>,

*Hamada A*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Hamada%20\

A%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_R\

VAbstractPlusDrugs1>,

*Nakane Y*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Nakane%20\

Y%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_R\

VAbstractPlusDrugs1>,

*Okazaki Y*

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Okazaki%2\

0Y%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_\

RVAbstractPlusDrugs1>.

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