Abstract
Autism spectrum disorders (ASDs) is a heterogeneous group of neurodevelopmental
disorders with a significant genetic component as shown by family and twin studies.
However, only a few genes have repeatedly been shown to be involved in the
development of ASDs. The aim of this study has been to identify possible ASD
susceptibility genes.
Genome screens in ASD patients suggest possible susceptibility gene regions on
almost every chromosome. We identified four ASD patients with chromosomal
rearrangements, two of which were familial rearrangements involving one of these
putative susceptibility gene regions and two were de novo rearrangements. We
characterised all chromosomal breakpoints at the molecular level with Fluorescence in
situ hybridization (FISH) and Southern blot analysis when necessary. In addition,
Bacterial artificial chromosome (BAC) array-CGH (Comparative genome
hybridization) was performed for all four patients. By combination of these methods we
identified several putative susceptibility genes for ASDs. Expression patterns were
established for several of these genes by Quantitative PCR (Q-PCR) or in situ
hybridization and one gene was sequenced in 157 ASD patients. Our results support a
complex genetic basis of ASDs and that detailed molecular dissection of patients with
inherited as well as de novo chromosomal rearrangements may reveal information about
susceptibility genes for ASDs. In addition, two of the candidate susceptibility genes
identified provide a potential link between a genetic predisposition and an environmental
factor (stress) that in a mouse model system result in a male specific effect. Accordingly,
these two autosomal genes are candidates for the male preponderance in ASDs.
disorders with a significant genetic component as shown by family and twin studies.
However, only a few genes have repeatedly been shown to be involved in the
development of ASDs. The aim of this study has been to identify possible ASD
susceptibility genes.
Genome screens in ASD patients suggest possible susceptibility gene regions on
almost every chromosome. We identified four ASD patients with chromosomal
rearrangements, two of which were familial rearrangements involving one of these
putative susceptibility gene regions and two were de novo rearrangements. We
characterised all chromosomal breakpoints at the molecular level with Fluorescence in
situ hybridization (FISH) and Southern blot analysis when necessary. In addition,
Bacterial artificial chromosome (BAC) array-CGH (Comparative genome
hybridization) was performed for all four patients. By combination of these methods we
identified several putative susceptibility genes for ASDs. Expression patterns were
established for several of these genes by Quantitative PCR (Q-PCR) or in situ
hybridization and one gene was sequenced in 157 ASD patients. Our results support a
complex genetic basis of ASDs and that detailed molecular dissection of patients with
inherited as well as de novo chromosomal rearrangements may reveal information about
susceptibility genes for ASDs. In addition, two of the candidate susceptibility genes
identified provide a potential link between a genetic predisposition and an environmental
factor (stress) that in a mouse model system result in a male specific effect. Accordingly,
these two autosomal genes are candidates for the male preponderance in ASDs.
| Original language | English |
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| Publisher | Museum Tusculanum |
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| Publication status | Published - 2007 |