Which chromosome causes autism

Autism: Genetic Diversity and Paternal Risks

New Haven / Seattle / Boston - The clinical diversity of autistic disorders seems to be based on an at least as wide spread of genetic causes. Three genetic studies carried out at great expense have uncovered a number of potential autism genes. A common genetic denominator was rarely seen.

The spectrum of autistic diseases ranges from early childhood autism with a lack of language development and intellectual disabilities to Asperger's Syndrome, in which disorders of social interaction and communication can be paired with so-called island talents. A common cause of these different diseases seems unlikely, but due to the pronounced familial accumulation, great efforts are made to find the underlying genes. Modern sequencing machines make this possible today at a reasonable cost.

The team led by Matthew State from Yale University in New Haven was able to sequence all protein-coding genes (exomes) of 928 people from 238 families in which a child suffered from autism spectrum disorder (ASD) (Nature 2012; doi: 10.1038 / nature10945). The researchers found 279 somatic “de novo” mutations that developed in parents' life and were passed on to their children.

Only one mutation was found in two unrelated children, making a coincidence very unlikely. The mutation in the SCN2A gene affects a voltage-dependent sodium channel and a connection with a developmental disorder of the brain is entirely plausible. However, the mutation is only likely to occur in a minority of patients with ASD and is only one of many causes of the disease.

Evan Eichler's team from the University of Washington in Seattle did not succeed in finding a mutation that would explain many diseases (Nature 2012; doi: 10.1038 / nature10989). Exome sequencing of 677 people from 209 families with an ASD child led to the discovery of 248 de novo mutations, 120 of which were classified as serious.

These were individual cases that did not provide a basis for a genetic test. There was a mutation in the SCN1A gene, which is somewhat in agreement with the data from the Yale group. Eichler's overall impression is that ASD has very diverse genetic causes. In addition, there may be environmental influences that were not the subject of the investigation.

Since the number of de novo mutations increases with the age of the parents, the risk of passing them on to the children also increases. This danger seems to exist especially with the fathers. De novo mutations were four times more common than in the mothers.

The Autism Sequencing Collaborative Group headed by Mark Daly from the Broad Institute in Boston, which sequenced the genes of 175 ASD patients and their healthy parents (Nature 2012; doi: 10.1038 / nature11011), has found further de novo mutations. Daly suspects that, in addition to SCN2A, the genes KATNAL2 and CHD8 are also possible causes of autism.

The function of KATNAL2 is unknown. CHD8 is a transcription factor that is said to affect chromatin, the "packaging material" for DNA in the cell nucleus. Mutations could prevent genes required for brain development from being read. © rme / aerzteblatt.de