User:Kelsidc/Main Sandbox

Epigenetics of Autism--People playing in this sandbox are: Kelsi Cox, Valentina, Ria, Christina

Article Evaluation/summary of proposed changes:

• C class article of mid importance.
• Very little activity in the talk page, which is surprising, because this article is within the scope of several WikiProjects (it was created by a UT class with WikiEducation and is in the scope of WikiProject Autism).
• This article is relevant; there are several hundred review articles matching the search criteria for this topic on PubMed, so there's a sufficiently large body of research to support this article.
• This article is FAR too technical. There should be a broader overview of why the topic is important and why it's being researched.

• • The sections of this article need to be more clearly organized. The authors jumped into very technical discussions of the relevant research, without providing solid context and organization for each of these discussions. Also, there are too many technical tables in each of the sections, which make the article visually unappealing, difficult to grasp, and overly complicated. The tables should be removed, at least at the beginning of a new draft, and each of the sections should be reformatted with the explicit aim of providing basic context of their relevance, with many review articles for support.
  • The Lead needs a clearer definition of "epigenetics of autism." The lead starts with a discussion of Autism Spectrum Disorder, which is helpful because a definition of "autism" should be given first. However, I think it might be more helpful to define "epigenetics" first, then to give a broad overview of autism that links to relevant Wiki articles, and finally to focus on a broader picture of the application of epigenetics to autism.

• • • I think this order makes more sense because most readers will likely be familiar with ASD, but many will not be familiar with epigenetics, so it's better to start with the lesser-known terms in the Lead. That way, readers can quickly understand what the article is about rather than waiting for the third paragraph of the Lead.

• • • • Also, because links to articles generally contain snippets of the leads of those articles, having the best lead possible could increase the number of links to this article.

• • • It's been suggested that epigenetics of autism should be made a subsection of the article on autism, rather than being a separate article. Merging the two in this way could be helpful, but given how large the body of research is on this topic, I lean towards keeping the two articles separate. HOWEVER, this poses a slight difficulty, because the Lead of the epigenetics article provides inadequate context on the nature of autism and its relation to epigenetics. But that could be resolved by linking to the autism article, as I suggested above, provided that at least a few sentences of brief overview/summary is provided in this article, as well.

• This article needs fewer primary sources and more review/secondary sources.
• This references section of this article needs to be reformatted.

Potential review articles:

Genetics and epigenetics of autism: A Review.

Implication de l’épigénétique dans les troubles du spectre autistique : revue de la littérature [Epigenetics' implication in autism spectrum disorders: A review]

Epigenetics and autism.

Outline of Article

Lead:

• good Definition of autism and autism spectrum disorder
• good definition of epigenetics
• What are the general ways that epigenetics has been applied to autism?

Epigenetic Causes of ASD [or "Autism"?]

15q11-13 duplication

In humans, chromosome 15q11-13 is the location of a number of mutations that have been associated with Autism spectrum disorders (ASD).

Duplications of 15q11-13 are associated with about 5% of patients with ASD and about 1% of patients diagnosed with classical Autism. 15q11-13 in humans contains a cluster of genetically imprinted genes important for normal neurodevelopment. (Table 1) Like other genetically imprinted genes, the parent of origin determines the phenotypes associated with 15q11-13 duplications. "Parent of origin effects" cause gene expression to occur only from one of the two copies of alleles that individuals receive from their parents. (For example, MKRN3 shows a parent of origin effect and is paternally imprinted. This means that only the MKRN3 allele received from the paternal side will be expressed.) Genes that are deficient in paternal or maternal 15q11-13 alleles result in Prader-Willi or Angelman syndromes, respectively, and duplications in the maternal copy lead to a distinct condition that often includes autism. Overexpression of maternally imprinted genes is predicted to cause autism, which focuses attention to the maternally expressed genes on 15q11-13, although it is still possible that alterations in the expression of both imprinted and bilallelically expressed genes contribute to these disorders. The commonly duplicated region of chromosome 15 also includes paternally imprinted genes that can be considered candidates for ASD.

Genes on 15q11-13 can be classified into three main categories:

• GABA_A receptor genes:

Members of the GABA receptor family, especially GABRB3, are attractive candidate genes for Autism because of their function in the nervous system. Gabrb3 null mice exhibit behaviors consistent with autism and multiple genetic studies have found significant evidence for association. Furthermore, a significant decrease in abundance of GABRB3 has been reported in the brain of AS, AUT and RTT patients. Other GABA receptors residing on different chromosomes have also been associated with autism (e.g. GABRA4 and GABRB1 on chromosome 4p).

• Maternally imprinted genes:

There are two maternally imprinted genes in 15q11-13, UBE3A and ATP10A (Table 1) and both lie toward the centromeric end. Both these genes are important candidates for ASD. Significant decrease in UBE3A abundance has been observed in post mortem brain samples from patients with AUT, AS and RT. Patients with autism have also shown abnormalities in methylation of the UBE3A CpG island.

• Paternally imprinted genes:

Most of the genes in 15q11-13 are paternally expressed. Gene expression analysis of paternally expressed imprinted genes has revealed that, in some cases excess of maternal 15q11-13 dosage can cause abnormal gene expression of the paternally expressed genes as well (even though the paternal 15q11-13 is normal).

Regulation of gene expression in 15q11-13:

Regulation of gene expression in the 15q11-13 is rather complex and involves a variety of mechanisms such as DNA methylation, non-coding and anti-sense RNA.

The imprinted genes of 15q11-13 are under the control of a common regulatory sequence, the imprinting control region (ICR). The ICR is a differentially methylated CpG island at the 5′ end of SNRPN. It is heavily methylated on the silent maternal allele and unmethylated on the active paternal allele.

MeCP2, which is a candidate gene for Rett syndrome, has been shown to affect regulation of expression in 15q11-13. Altered (decreased) expression of UBE3A and GABRB3 is observed in MeCP2 deficient mice and ASD patients. This effect seems to happen without MeCP2 directly binding to the promoters of UBE3A and GABRB3. (Mechanism unknown) However, chromatin immunoprecipitation and bisulfite sequencing have demonstrated that MeCP2 binds to methylated CpG sites within GABRB3 and the promoter of SNRPN/SNURF.

Furthermore, homologous 15q11-13 pairing in neurons that is disrupted in RTT and autism patients, has been shown to depend on MeCP2. Combined, these data suggest a role for MeCP2 in the regulation of imprinted and biallelic genes in 15q11-13. However, evidently it does not play a role in the maintenance of imprinting.

Free to a Good Home

Computational Epigenetics

Article Evaluation/summary of proposed changes:

• Start class article of mid importance.

• • The sections that are present are helpful, but there simply isn't enough information on this page to make it useful.

• • • The "Applications in cancer epigenetics" section is helpful, but more information is needed to determine whether this is the primary application of computational epigenetics, and therefore whether this section is "well-balanced," or whether a more comprehensive view of the applications of computational epigenetics is suggested by the research.

• This article is within the scope of WikiProject Computational Biology and the Regulatory and Systems Genomics task force.
• This article is relevant; there are roughly a thousand review articles matching the search criteria for this topic on PubMed, so there's a sufficiently large body of research to write a lengthy article.
• There are only about six sources cited. Some of the sections have no citations, such as the "applications in cancer epigenetics" subsection and the "Definition" section. So, several sources should be added. It might be helpful to keep the section on "Epigenetics Databases," but it might not be needed, especially since there are so few sections and this is too technical compared to the rest of the article.
• There are not enough linked articles. There are no linked articles in the "Definition" section, for example, which is problematic because there are several technical terms used that aren't otherwise defined in the article. This article needs a clearer definition.

Potential review articles:

Computational epigenetics.

Computational methods and next-generation sequencing approaches to analyze epigenetics data: Profiling of methods and applications.

Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes.