Erin's research paper

Erin Carrow
Developmental genetics
Autism

Autism is a severe neurodevelopmental disorder. It is considered to be one of the most devastating diseases affecting children. There are three main symptoms seen in autism: 1) deficits in social interactions and understanding, 2) abnormal communication and/or language development, and 3) restricted interests and repetitive, stereotyped behaviors (1). It has been estimated that the prevalence of autism is 1 in 150 individuals (2). Recent estimates place the prevalence of autism in males versus females as 4:1 (3). For this reason it is believed that the sex chromosomes, as well as changes in the epigenetic regulatory mechanisms, are involved in the development of autism.

In normal development, there are certain genes on the X chromosomes that are highly methylated in order to prevent transcription and translation of those particular genes. Different methylation patterns are found in the male chromosomes than the female to keep more than one of the same gene from being active. This is known as X chromosome inactivation. X chromosome inactivation (XCI) is a process where the majority of the genes on one of the X chromosomes in females are inactivated by epigenetic regulation. It has been shown that XCI skewing is increased in diseases that are relevant to autism such as Rett syndrome.

In an analysis of an untranslated region (UTR) of bases in the MECP2 gene, a higher frequency of missense and 3’ UTR varients was found in autistic people.

Methyl-CpG-binding protein 2 (MECP2) is a key epigenetic regulator. According to Amir et. al. MECP2 mutations have been found in people with Rett syndrome (1999), this lead researchers to look at MECP2 in autistic people. Studies have shown that 79% of autistic cerebral cortex brain samples showed a defect in MeCP2 expression (citation). The decreased expression of MeCP2 has been correlated with increased MECP2 promoter methylation in male brain samples. Nagarajan et. al. demonstrated that a region 0.6 kb upstream from the MECP2 gene in brain DNA showed a significant change in the amount of methylation in both sexes, in males it was unmethylated and XCI in females (2008).

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