Genetics2

From Pheno Wiki
Revision as of 15:21, 21 April 2010 by 128.97.66.134 (Talk) (Etiology)

Jump to: navigation, search

Etiology

Want more information about a
specific gene or gene group? Pick one of the categories below!
CadherinsNeuroligins/Neurexins/Shank3
METCNVs
ERK and P13KUbiquitin
RELNNeurotrophins
CNTNAP-2Serotoninergic, GABAergic,
and glutamatergic pathways
EIF4EPTEN
NeurotrophinsOxytocin and AVP
Cav1.2NCAM2
PLAUR




Recent studies have suggested that ASD in families where multiple members are affected by autistic traits may be caused more by genetic predisposition. In contrast, ASD in families where only one member displays autistic traits are more likely to be caused by rare gene mutations which have a large effect or by copy number variations. One way of studying this difference is by comparing autistic traits in unaffected family members from multiplex autism families to simplex autism families.5

Linkage and Association Studies

Successful linkage studies in the past have been mostly based on affected sibling-pair designs in multiplex families. However, there were no genome wide significant results probably because of small effect sizes that were a result of any single gene. Even large scale studies showed only minor overlap, likely because of variety of phenotypes in ASD. Recently though, use of endophenotypes and QTL mapping have increased the power of linkage and association studies.

Endophenotypes can help genetic studies by defining more etiologically homogenous subgroups. Furthermore, endophenotypes are measurable in both affected and control groups, thus allowing for larger sample sizes. Language phenotypes such as the age at which the child speaks their first word, are very promising endophenotypes because they show significant linkage in many samples and the support has been lent at implicating the 7q region to this language development, thereby raising hypothesis that the 7q region is home to other loci that are associated with the autism language phenotype3.


Some areas of investigation include

  1. Methylation
  2. Copy-Number Variation


Main Page
Back




Analytical Techniques

Citations

1. Schmitz C. Autism: neuropathology, alterations of the GABAergic system, and animal models.Int Rev Neurobiol. 2005;71:1-26. PMID 16512344

2. Jones, J.R. et. al. Hypothesis: Dysregulation of Methylation of Brain-Expressed Genes on the X Chromosome and Autism Spectrum Disorders. American Journal of Medical Genetics Part A 146A:2213-2220 (2008). PMID 18698615

3. Lush, Molly et. al. Current Developments in the Genetics of Autism: From Phenome to Genome. J Neuropathol Exp Neurol. 2008 September; 67(9):829-837. PMID 18716561

4. Cook, E.H. and S. W. Scherer. Copy-number variations associated wtih neuropsychiatric conditions. Nature.2008 October;455(16) 919-23. PMID 18923514

5. Hoekstra RA, et. al. Autistic traits in simplex and multiplex autism families: Focus on unaffected relatives.Am J Med Genet B Neuropsychiatr Genet. 2010 Jan 5;153B(1):356-8. PMID 19367575