MOLECULES OF THE MIND
PSYCHIATRIC TIMES www.psychiatrictimes.com 17
Fishing and Autism
Continued from page 12
on such complex challenges as autism. When it was, it proved to be invaluable in the autism-screening procedures.
The data Researchers first had to find consan- guineous families with autistic chil- dren. They established a collaborative network called the Homozygosity Mapping Collaborative for Autism (HMCA) in the Middle East and throughout Eurasia.1 The reason for this geographic localization has to do with statistical access. It is quite com-
mon in the Middle East for cousins to marry each other. Since the families tend to be large, the researchers rea- soned they would most likely find persons that met both their genetic and behavioral criteria. They hit pay dirt. The researchers were able to find 88 consanguineous families with autistic children.
The investigators next scanned the genomes of all participants at high resolution. They were looking for a wide variety of chromosomal aberra- tions, such as inversions, deletions, duplications, and something called copy-number variations.
After exhaustive screening, the re- searchers found that 6 chromosomal
regions in the HMCA sample had in- herited, homozygous deletions. These deletions varied in size from a low of 18 kilobases to more than 880 kilobases.
Exactly what genes were on these important chromosomal regions, and how might their characterization in- crease our understanding of autism? To discover what happened next, we need to switch fishing protocols. We are going to tie up our large fishing trawlers, which is what homozygous mapping is, and inspect the catch. Once inspected, the next steps will then involve breaking out our much smaller fishing poles, putting some bait on the end, and casting our lines
back into the genomic waters.
As you see in the Figure, a large number of genes were netted in this experiment. I will describe exactly what was in the catch and how this in- creases our understanding of autism next month.
Dr Medina is a developmental molecular bi- ologist and private consultant, with research interests in the genetics of psychiatric disorders.
1. Fliesler N. Middle Eastern families yield intriguing clues to autism. Harvard Science: Medicine + Health. July 10, 2008. http://www.harvardscience.harvard. edu/medicine-health/articles/middle-eastern- families-yield-intriguing-clues-autism. Accessed De- cember 9, 2008. ❒
The genetic basis of autism
Shown below are some of the genes whose mutations result in autism or autism-related disorders. This list is limited to copy-number variations or specific chromosomal abnormalities. There are many other mutation categories involved in autism, ranging from point mutations and deletion mutations to chromosomal inversions.
There does not appear to be any consistent story regarding biological functionality that emerges from the examination of these sequences. Some of the genes listed below are involved in endosomal trafficking, others in neuronal cell adhesion. Some are clearly ion channels. The genes determined to be involved in autism by the homozygous mapping technique described in the text are red.
Name of protein
A2BP-1 CNTNAP-2 CNTN3 D1A1 MECP-2 NHE9 NRXN-1 PCDH10 RNF-8 SCN7A SHANK-3 UBE3A
Ataxin 2-binding protein 1
Contactin-associated protein-like 2
Deleted in autism 1
Methyl-CpG-binding protein 2
Na+/H + exchanger isoform 9
Ring finger 8
Na+ channel, voltage-gated, type VII
SH3 and multiple ankyrin repeat domains 3
Ubiquitin protein ligase E3A