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Links between genetics and pathophysiology in the autism spectrum disorders.

Holt R, Monaco AP - EMBO Mol Med (2011)

Bottom Line: Significant collaborative effort has been made over the last 15 years in an attempt to unravel the genetic mechanisms underlying these conditions.This has led to important discoveries, both of the roles of specific genes, as well as larger scale chromosomal copy number changes.Here, we summarize some of the latest genetic findings in the field of ASD and attempt to link them with the results of pathophysiological studies to provide an overall picture of at least one of the mechanisms by which ASD may develop.

View Article: PubMed Central - PubMed

Affiliation: The Wellcome Trust Centre for Human Genetics, University of Oxford, UK.

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Related in: MedlinePlus

General overview of the potential route of the underlying mechanisms of ASDInteractions between the environment and genetic factors, including point mutations, CNVs and epigenetics, determine the development of the brain. Combinations of factors resulting in decreased connectivity between regions of the brain cause a decreased ability to integrate information. This expresses itself at the level of behaviour in the individual as alterations in the areas of social interaction, communication and behaviour, the extent of the variation in each area depending on the environmental and genetic variables, leading to the range of ASD phenotypes observed.
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fig02: General overview of the potential route of the underlying mechanisms of ASDInteractions between the environment and genetic factors, including point mutations, CNVs and epigenetics, determine the development of the brain. Combinations of factors resulting in decreased connectivity between regions of the brain cause a decreased ability to integrate information. This expresses itself at the level of behaviour in the individual as alterations in the areas of social interaction, communication and behaviour, the extent of the variation in each area depending on the environmental and genetic variables, leading to the range of ASD phenotypes observed.

Mentions: Therefore, there appears to be strong concordance between observed structural alterations in autistic brains and the underlying genetic susceptibility loci identified. However, this does not mean that this is the only mechanism involved in ASD susceptibility (Fig 2). For example, in a recent pathway analysis Yaspan et al identified 17 pathways, including the uridine diphosphate glycosyltransferase 2 protein family and genes involved in synthesis and degradation of ketone bodies. The latter could affect γ-aminobutyric acid (GABA) levels, a neurotransmitter system implicated in ASD (Yaspan et al, 2011).


Links between genetics and pathophysiology in the autism spectrum disorders.

Holt R, Monaco AP - EMBO Mol Med (2011)

General overview of the potential route of the underlying mechanisms of ASDInteractions between the environment and genetic factors, including point mutations, CNVs and epigenetics, determine the development of the brain. Combinations of factors resulting in decreased connectivity between regions of the brain cause a decreased ability to integrate information. This expresses itself at the level of behaviour in the individual as alterations in the areas of social interaction, communication and behaviour, the extent of the variation in each area depending on the environmental and genetic variables, leading to the range of ASD phenotypes observed.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3377085&req=5

fig02: General overview of the potential route of the underlying mechanisms of ASDInteractions between the environment and genetic factors, including point mutations, CNVs and epigenetics, determine the development of the brain. Combinations of factors resulting in decreased connectivity between regions of the brain cause a decreased ability to integrate information. This expresses itself at the level of behaviour in the individual as alterations in the areas of social interaction, communication and behaviour, the extent of the variation in each area depending on the environmental and genetic variables, leading to the range of ASD phenotypes observed.
Mentions: Therefore, there appears to be strong concordance between observed structural alterations in autistic brains and the underlying genetic susceptibility loci identified. However, this does not mean that this is the only mechanism involved in ASD susceptibility (Fig 2). For example, in a recent pathway analysis Yaspan et al identified 17 pathways, including the uridine diphosphate glycosyltransferase 2 protein family and genes involved in synthesis and degradation of ketone bodies. The latter could affect γ-aminobutyric acid (GABA) levels, a neurotransmitter system implicated in ASD (Yaspan et al, 2011).

Bottom Line: Significant collaborative effort has been made over the last 15 years in an attempt to unravel the genetic mechanisms underlying these conditions.This has led to important discoveries, both of the roles of specific genes, as well as larger scale chromosomal copy number changes.Here, we summarize some of the latest genetic findings in the field of ASD and attempt to link them with the results of pathophysiological studies to provide an overall picture of at least one of the mechanisms by which ASD may develop.

View Article: PubMed Central - PubMed

Affiliation: The Wellcome Trust Centre for Human Genetics, University of Oxford, UK.

Show MeSH
Related in: MedlinePlus