Links of DNA Deficiency to Autism Strengthened



 In the past, small communities in Finland lived for years in seclusion.  The resulting inbreeding caused the isolation of certain rare genes.

In one such group the incidence of autism and schizophrenia was marked.  A study of this community has led to findings that strengthen the convincing connection between defective cellular processes and autism, schizophrenia and other conditions.

Nelson Freimer and his associates at the University of California, Los Angeles, examined the genetic material of this community in comparison with the larger Finnish population.

They found that a portion of DNA from one of the chromosomes— number 22—was missing in 18 of the 173 people sampled from this cloistered group. Only 1 in 1586 individuals sampled from the rest of the population lacked this DNA.

The testing results support the hypothesis that those suffering from schizophrenia or cognitive impairments have a deficit in this portion of DNA.  This helps us to understand how such disorders are interrelated with biological functioning.

Taking out the DNA is like removing the backbone of a chromosome. Chromosomes are the structures that hold our genes, and genes provide instructions to our bodies about how to develop and function, and govern characteristics such as hair color, blood type and even susceptibility to disease.

But further investigation by a team led by Weidong Wang from the US National Institute on Aging in Baltimore, Maryland disclosed that the deleted region normally contains a specific gene that makes an enzyme called topoisomerase III beta (TOP3B).

The supporting structure of each chromosome is a molecule called deoxyribonucleic acid (DNA).   Genes are genetic material arranged in a line along the DNA molecule.  DNA is in the shape of a double helix, like a twisted rope ladder.  The rungs of the ladder are collections of carbon, hydrogen and oxygen atoms called nitrogenous bases.

Genes create special proteins called enzymes that read and copy (or “transcribe”) the DNA code. The enzymes use this transcription to “unzip” a segment of the DNA to create ribonucleic acid (RNA).  How this happens is that this portion unwinds and splits in half.  Then sugars, phosphates and “free” bases, which make up nucleotides, attach to the bases in the exposed part of the DNA half.  The bases have to match up a particular way, because certain bases always pair  with other bases.  For example, the base adenine (A) always matches up with thymine (T).  The result is a strand attached to the DNA half, which is RNA.  RNA is a reverse copy of the DNA strand.  While the DNA molecule is double stranded (two sides of the ladder), the RNA has only a single strand.  The RNA detaches itself from the DNA half.  The two strands of the DNA then reunite.

Meanwhile the RNA, now designated as the messenger RNA, or mRNA, travels out of the nucleus of the cell—where all this is taking place—to the cytoplasm or outer portion of the cell and meets the ribosome, a granule of cytoplasm that uses the DNA recipe to create a certain protein. Protein is required by the human body to build, maintain and repair body tissues.  One type of cell where all of this occurs is the neuron, which is the essential part of the nervous system, communicating information throughout the body. Neurons are also called “nerve cells.”

If TOP3B is absent, the copying of the DNA half to create RNA will not happen as it should, because TOP3B plays a part in regulating the winding and unwinding of RNA. This may lead to a change in the shape of the RNA, which would affect the creation of proteins through the RNAs’ interactions with the ribosomes.  The way in which neurons grow and connect would be impacted. Faulty neural connections have been linked to schizophrenia, autism, and fragile X syndrome.

While a look at a segregated Finnish community showed an association between a want of DNA and autism, a study by Calleb Weber and colleagues at the University of Oxford of 181 autistic individuals disclosed that many had a deficiency or surplus of genes significant to the transmission of neuronal signals.  At the center of a network of genes, depicted in a computer reconstruction, areas in which there were too few or too many genes caused the signals to be diverted.

These results make more certain the correlation of genes with autism and other syndromes, which has already been fairly well established.


By:  Tom Ukinski



New Scientist (I) and New Scientist (II);  The Tech Museum of Innovation;; and National Human Genome Research Institute