Pedigree Puzzle: Why is there a Gender Bias in Autism?
★ Autism Spectrum Disorders are more frequently diagnosed in males than females: commonly four times as often, although that bias climbs to 11:1 in the case of Asperger’s syndrome. The underlying reasons are complex and many plausible theories have been proposed. Let’s begin by looking at one example of pronounced gender bias in autism, seen in this pedigree chart. A pedigree chart is used by geneticists to track genotypes (such as a particular mutation) and phenotypes (such as appearance of a disease) over many generations of an extended family. If you’ve never deciphered one before, this is your chance to figure out what those squares and circles mean!
★ How to Read a Pedigree Chart: To begin, girls are circles and boys are squares – helpfully colorized to pink or blue to fit the stereotype 😉 There are four generations in this chart (I-IV), each in a separate row. Offspring from a pair are shown by the T bars: for example, the first pair (now deceased) had four children, two males and two females. One of the females produced the four children shown in generation III. Progeny from three pairs are shown in generation IV. Makes sense so far?
★ Linking Genes to Autism: Back to the Science. Researchers monitored the SHANK1 gene in ~2,600 people with autism and ~15,000 “controls”. They found a large deletion that wiped out most of one copy of the gene in four people with autism. Three were in the family shown in the pedigree chart. None in the control group had this deletion, so this was a statistically significant difference. In gene speak, we say there is a Copy Number Variation (CNV) in this gene. The Shank proteins act as scaffolds around which the synapse, or junction between nerve cells, is built. Other SHANK genes have already been linked to autism, so they used pedigree analysis on SHANK1. Six members of the family carried the CNV but surprisingly, only males with CNV were diagnosed with autism (labeled A in the chart). In case you are wondering, SHANK1 is not on the X chromosome, so the gene is not sex linked. So why are only males in this family autists even though they carry the same mutation as some of the females? This is an extreme case of gender bias in autism. Although the precise answer is not known for the SHANK1 mutation, we will follow some testable hypotheses in future posts!
★ Reference (free read): Shank1 deletions in males with autism spectrum disorder. Sato et al., 2012
Links to my older posts on autism are here:
The Genetics of Autism ▶ http://goo.gl/AzTuAX
Autism Spectrum Disorders from Mechanism to Therapy ▶ http://goo.gl/y751QH
A Part of the Puzzle: NHE9 and Autism ▶http://goo.gl/YXbOkN