Abstract
The etiologic paradigm of complex human disorders such as autism is that genetic and environmental risk factors are independent and additive, but the interactive effects at the epigenetic interface are largely ignored. Genomic technologies have radically changed perspective on the human genome and how the epigenetic interface may impact complex human disorders. Here, I review recent genomic, environmental and epigenetic findings that suggest a new paradigm of "integrative genomics" in which genetic variation in genomic size may be impacted by dietary and environmental factors that influence the genomic saturation of DNA methylation. Human genomes are highly repetitive, but the interface of large-scale genomic differences with environmental factors that alter the DNA methylome such as dietary folate is under-explored. In addition to obvious direct effects of some environmental toxins on the genome by causing chromosomal breaks, nonmutagenic toxin exposures correlate with DNA hypomethylation that can lead to rearrangements between repeats or increased retrotransposition. Since human neurodevelopment appears to be particularly sensitive to alterations in epigenetic pathways, a further focus will be on how developing neurons may be particularly impacted by even subtle alterations to DNA methylation and proposing new directions towards understanding the quixotic etiology of autism by integrative genomic approaches.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 862-869 |
| Number of pages | 8 |
| Journal | Epigenetics |
| Volume | 6 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2011 |
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Keywords
- Alu
- Autism
- Copy number variation
- DNA methylation
- Environmental exposures
- Epigenetics
- Epigenomics
- Folate
- Folic acid
- Genomics
- LINE-1
- MeCP2
- Neurodevelopment
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
Cite this
A genomic point-of-view on environmental factors influencing the human brain methylome. / LaSalle, Janine M.
In: Epigenetics, Vol. 6, No. 7, 07.2011, p. 862-869.Research output: Contribution to journal › Article
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TY - JOUR
T1 - A genomic point-of-view on environmental factors influencing the human brain methylome
AU - LaSalle, Janine M
PY - 2011/7
Y1 - 2011/7
N2 - The etiologic paradigm of complex human disorders such as autism is that genetic and environmental risk factors are independent and additive, but the interactive effects at the epigenetic interface are largely ignored. Genomic technologies have radically changed perspective on the human genome and how the epigenetic interface may impact complex human disorders. Here, I review recent genomic, environmental and epigenetic findings that suggest a new paradigm of "integrative genomics" in which genetic variation in genomic size may be impacted by dietary and environmental factors that influence the genomic saturation of DNA methylation. Human genomes are highly repetitive, but the interface of large-scale genomic differences with environmental factors that alter the DNA methylome such as dietary folate is under-explored. In addition to obvious direct effects of some environmental toxins on the genome by causing chromosomal breaks, nonmutagenic toxin exposures correlate with DNA hypomethylation that can lead to rearrangements between repeats or increased retrotransposition. Since human neurodevelopment appears to be particularly sensitive to alterations in epigenetic pathways, a further focus will be on how developing neurons may be particularly impacted by even subtle alterations to DNA methylation and proposing new directions towards understanding the quixotic etiology of autism by integrative genomic approaches.
AB - The etiologic paradigm of complex human disorders such as autism is that genetic and environmental risk factors are independent and additive, but the interactive effects at the epigenetic interface are largely ignored. Genomic technologies have radically changed perspective on the human genome and how the epigenetic interface may impact complex human disorders. Here, I review recent genomic, environmental and epigenetic findings that suggest a new paradigm of "integrative genomics" in which genetic variation in genomic size may be impacted by dietary and environmental factors that influence the genomic saturation of DNA methylation. Human genomes are highly repetitive, but the interface of large-scale genomic differences with environmental factors that alter the DNA methylome such as dietary folate is under-explored. In addition to obvious direct effects of some environmental toxins on the genome by causing chromosomal breaks, nonmutagenic toxin exposures correlate with DNA hypomethylation that can lead to rearrangements between repeats or increased retrotransposition. Since human neurodevelopment appears to be particularly sensitive to alterations in epigenetic pathways, a further focus will be on how developing neurons may be particularly impacted by even subtle alterations to DNA methylation and proposing new directions towards understanding the quixotic etiology of autism by integrative genomic approaches.
KW - Alu
KW - Autism
KW - Copy number variation
KW - DNA methylation
KW - Environmental exposures
KW - Epigenetics
KW - Epigenomics
KW - Folate
KW - Folic acid
KW - Genomics
KW - LINE-1
KW - MeCP2
KW - Neurodevelopment
UR - http://www.scopus.com/inward/record.url?scp=79960118297&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960118297&partnerID=8YFLogxK
U2 - 10.4161/epi.6.7.16353
DO - 10.4161/epi.6.7.16353
M3 - Article
C2 - 21617367
AN - SCOPUS:79960118297
VL - 6
SP - 862
EP - 869
JO - Epigenetics
JF - Epigenetics
SN - 1559-2294
IS - 7
ER -