The 90% conundrum

Hi Connie,

I read the articles on your home page about the recent report on microscopic variants found on chromosome 16P.11. The article includes one of the most repeated statements in genetic studies of autism, 'Autism is 90% heritable'. That heritability estimate is based on the Gold Standard twin study published by Bailey et al in 1995.

The new finding also noted that the majority of cases where genetic variants reported in chromosome 16P.11 were spontaneous mutations that were not found in the parent(s). Wigler et al earlier this year published his 'Unified Theory of Autism' based in part on Ian data. In Science Daily, Wigler suggested that 90% of autism cases were sporadic, new mutations in the affected child that were not present in the parent(s).

If the majority of autism cases are sporadic, 'caused' by a de novo mutation in the affected child but the mutation is not present in the parent(s) then there exists two models of autism that are incompatible with each other, the 90% conundrum.

By inference, since the parents do not possess the genetic variant, they are unaffected, which raises important questions about the validity of the Broad Autism Phenotype and the entire polygenic hypothesis.

My question is, how does IAN's editorial board respond to this important question which relates to two competing theories which are incompatible to each other.

Perhaps you might ask Dr. Zimmerman who commented on the article you posted on the home page of IAn.

Thanks

Hi RAJ!

You make such a good point here. I think what is clear is that there are two competing theories about genetics and autism. One focuses on finding a susceptiblity gene -- some gene passed down through families that increases a child's risk of having autism. The other is more complex, and involves new discoveries about spontaneous genetic mutations and de novo copy-number variations that arise in a sperm, egg, or fertilized egg, but are not passed from a parent to a child in the sense that the variation was part of the parent's overall genetic code. (In other words, the child has this genetic variation, but the parent doesn't.)

In truth, because genetics is such a rapidly evolving field, it is too soon to declare whether one theory or the other is right...or whether both are in different cases. As research continues to unfold, evidence will accumulate to support (or undermine) each theory.

According to the article about the finding of the mutation on Chromosome 16p11.2, they said it accounts for only 1%. Well, we don't know that for sure because this chromosome mutation is responsible for other diseases. So we are only seeing the tip of the iceberg.
Yes, autism is without question genetic but the real question is; what causes these microdeletions in the chromosomes to become a health problem? It involves the protein that this chromosome encodes which is the Tamm Horsfall Protein. They already discovered several years ago that this is the chromosome responsible for certain kidney diseases. This protein, also called the Uromodulin protein has a major role in cellular immunity. This genetic finding proves that those suffering from autistic symptoms have an underlying immunological response that is creating inflammation and subsequent flairs presenting themselves behaviorally.
Sadly, we are dealing with ASD and with the Kidney disease version of this mutation within the same family over a couple generations. This is the only reason we are this informed! This chromosome is causing too many problems for us and we pray everyday that a proper immune based treatment or protocol will be established so that the suffering can cease.