Understanding Genetics: Y-Chromosome

In the recent years less information has become available on the involvement of the Y chromosome in Autism, but it has not vanished completely. Researchers used to believe that male prevalence of Autism proved that there were defects on the Y chromosome, but this theory was abandoned since it did not explain the female Autism population. Since then research has shifted more toward the X chromosome. The Y has not been completely forgotten. So what is the Y's involvement?

The Y in Families

In 2012 the Simons Foundation Autism Research Initiative (SFARI) published an article about the Y chromosome. According to SFARI, Autism affects four times more boys than girls. The male, or Y, chromosome carries a total of 60 genes. As we know from the X chromosome article approximately 1 in 1,000 boys are born with XXY genetics and approximately the same amount of boys are born with XYY genetics. This extra Y chromosome does come with similar impairment as Klinefelter (XXY). Citing a study from Pediatrics researchers discovered that half of the group with XYY genetics required additional Autism evaluation. Another article, cited by SFARI, found in the Archives of Disease in Childhood, was conducted to rate language and communication problems. Of their test group, 19% of the XYY genes were diagnosed with ASD, compared to 11% of the XXY group. These two studies have led SFARI to conclude that an extra Y copy of genes significantly boosts the risk of Autism in an individual. 

SFARI takes us to Chromosome 16. This chromosome, by either deletion or duplication, has been linked to one percent of ASD population. This chromosome is found on both the X and Y genes. Interestingly a variant of Chromosome 16 can be linked to other conditions, such as obesity. Two other chromosomes found on the Y chromosome are directly linked to Autism: NLGN4Y and USP9Y. These two have been linked to developmental delay disorders, seizures, and poor coordination, among others. 

Genes Associated with Autism

Another player in the Autism field is the RORA gene. RORA is a hormone dependent gene that acts as a master regulator of other genes. In 2011 a study was published which showed that testosterone and estrogen have opposite effects on RORA. Livescience.com published an article about this study. According to this article testosterone lowers the ability of cells to turn on the RORA gene, while estrogen raises the cells ability. Professor Hu, who we will discuss in a moment, proposes that a high level of fetal testosterone puts the fetus at risk for developing Autism. Preliminary research does not show that low RORA causes Autism, but it is associated. RORA deficiency, on the other hand, may explain the effects seen in Autism. One of RORA's functions is to protect neurons against inflammation and stress. Inflammation has been a huge research theory in the Autism community lately. It is also responsible for helping to maintain the body's circadian rhythm or the sleep/wake cycle, which could help explain sleep disturbances in Autism. According to Dr. Hu individuals with Autism have lower RORA levels in their brain tissue, when compared to typical brain tissue. 

In 2013, ASD Research published an article about RORA and Autism. Dr. Hu a professor of biochemistry at George Washington University discovered that RORA regulates a large number of genes associated with Autism. RORA appears to play a role in the regulation of androgen and estrogen. An over production or under production of RORA seems to impact six other genes directly related to Autism, one of which is another NLGN gene. This may contribute to the male bias of the ASD spectrum. 

To read more about Chromosome 16 please read this article. 

To read more about the role of sex hormones in Autism, please read this article. 

I hope this helps to give you a basic understanding of the Y Chromosome and RORA gene. We are here to support you on your Autism journey. For more interesting topics please read our blog and follow us on Facebook.