Monday, April 30, 2012

Research Blog on “Genome-wide scan for loci of Asperger syndrome”

 
Asperger’s syndrome is a type of pervasive development disorder. Although Asperger’s syndrome is similar to autism, there are some major differences. Children with Asperger’s syndrome typically function better than those with autism. Furthermore, children with Asperger’s syndrome generally have normal intelligence and near normal language development. Since the first observations, problems with social interaction have been frequently observed in the family members of patients with Asperger’s syndrome and thus suggest familial and perhaps genetic aggregation of the syndrome. Several reports, including the original description by Hans Asperger (1944), have suggested that AS has a strong gnenetic component. In this research, the experimenters have performed a genome-wide scan on Finnish families specifically for Asperger Syndrome with a strictly defined phenotype, an observable characteristics of an individual resulting from the interaction of its genotype with the environment.


The aim of the current study, “Genome-wide scan for loci of Asperger syndrome,” is to identify genetic loci, a position of a gene, for Asperger Syndrome by analyzing Finnish families in which both the Asperger syndrome’s patient and one of their parents was affected.This analysis is done through a method called genome-wide scan. During a genome wide scan, the DNA, which has been extracted from the blood sample, has markers placed along the chromosomes, each of which are different sizes. This method of observation allows researchers to see whether a gene for the disorder lies near one of the markers to determine where the loci of Asperger Syndrome are. By identifying the loci of Asperger Syndrome, in the future, doctors can identify the loci that cause AS and perhaps fix or prevent the symptoms from happening even before the baby is born.
The method to analyze the Finnish families includes dividing these families into four groups: Asperger syndrome (narrow classification), Asperger syndrome (broad classification), unaffected, and other disorder. They are divided depending on health background and the results of their diagnostic interviews, which includes questions about behaviors that are frequently presented in individuals with AS. Individuals who fulfilled all criteria for AS during the diagnostic interviews will be labeled as “affected individuals, narrow classification” while individuals who had Asperger-like features but did not fulfil all the diagnostic criteria will be labeled as “affected individuals, broad classification.” By analyzing individuals with Asperger syndrome (whether they are narrow classification or broad classification), the unaffected, and the ones presented with other disorders, researchers can compare loci, identify the loci overlaps between people with AS, find the connection between the loci and the origin of the disorder, and deduce its connection with other genetic disorder.


After dividing the participants into different groups, genome wide scan is performed. This is done by extracting DNA through blood from the participants, placing markers in the DNA, performing polymerase chain reaction, and conducting gel electrophoresis. The tools for PCR and gel electrophoresis are stated in the videos
                                                Polymerase Chain Reaction

                                                       Gel Electrophoresis

After gel electrophoresis, data were extracted from the gels and the genotypes were assigned and verified.

The results of the genome wide scans are as followed: In the initial scan to find the overlapping of loci, Zmax>1.5 was observed on nine chromosomal regions, 1q21–22, 3p14–24, 3q25–27, 4p14, 4q32, 6p25, 6q16, 13q31–33 and 18p11. In the fine mapping stage, the highest two-point LOD scores were observed on chromosomes 1q21–22 (D1S484, Zmax dom=3.58), 3p14–24 (D3S2432, Zmax dom=2.50) and 13q31–33 (D13S793, Zmax dom=1.59). The loci on 1q21–22 and 3p14–24 overlap with previously published autism susceptibility loci, and the loci on 1q21–22 and 13q31–33 overlap with the reported schizophrenia susceptibility loci. This process is called linkage analysis. 

                                                                  Gene Linkage Study 
 

            In conclusion, the evidence for linkage was observed in the Asperger material throughout the 3q25-27 regions. To our knowledge, this study is the first genome wide screen in Asperger syndrome. Interestingly, the identified AS loci are overlapping some susceptibility loci reported earlier for autism and schizophrenia. The overlapping linkage regions between AS and other neuropsychiatric disorders do not necessarily mean shared genes, but rather implies that these genomic regions deserve additional analyses in the clinical study samples to find the relationship between these overlap linkage regions.
Other causes of Asperger Syndrome
In this article, it is implied that there is a linkage between Asperger syndrome and genes. Thus, the researchers are stating that Asperger Syndrome is a genetic disorder that is caused by AS susceptibility loci. However, other research studies show that Asperger syndrome is not caused only caused by genetic factor but is also caused by other factors.

mirror neuron theory

The mirror neuron system (MNS) theory hypothesizes that alterations to the development of the MNS interfere with imitation and lead to Asperger's core feature of social impairment. For example, one study found that activation is delayed in the core circuit for imitation in individuals with Aspergers syndrome. This theory maps well to social cognition theories like the theory of mind, which hypothesizes that autistic behavior arises from impairments in ascribing mental states to oneself and others, or hyper-systemizing, which hypothesizes that autistic individuals can systematize internal operation to handle internal events but are less effective at empathizing by handling events generated by other agents. Other possible mechanisms include serotonin dysfunction and cerebellar dysfunction.

Possible environmental causes of Asperger's
• Infectious disease
• Heavy metal toxicity
• Certain vaccinations

• Perinatal factors
• Stress.

Resources:
"New Genetic Study Of Asperger Syndrome, Autistic Traits And Empathy." Medical News Today. MediLexicon International, 17 July 2009. Web. 30 Apr. 2012. <http://www.medicalnewstoday.com/releases/157802.php>.
"TO WHAT EXTENT DO GENES CAUSE AUTISM?" Autism, PDD-NOS & Asperger's Fact Sheets. Web. 30 Apr. 2012. <http://www.autism-help.org/autism-heritability-parents.htm>.
Perry, Mark. "Asperger Syndrome Cause." Health Guidance. Web. 30 Apr. 2012. <http://www.healthguidance.org/entry/11545/1/Asperger-Syndrome-Cause.html>.
Stöppler, Melissa Conrad. "MedicineNet.com." MedicineNet. David Perlstein. Web. 30 Apr. 2012. <http://www.medicinenet.com/asperger_syndrome/page3.htm>.
Leite, Embrapa De. "BMC Genomics | Full Text | Genome Wide Scan for Quantitative Trait Loci Affecting Tick Resistance in Cattle (Bos Taurus X Bos Indicus)." BioMed Central. BMC Genomics, 30 Apr. 2010. Web. 30 Apr. 2012. <http://www.biomedcentral.com/1471-2164/11/280>.

2 comments:

  1. I remember watching a video last year about a family that had six children, and each of these six children was affected by some form of mental disorder ranging from mild to severe on the autistic spectrum. While watching, I wondered what were the chances that every child in the family was affected by the mental condition. The oldest boy in this family had asperger syndrome, and although he had a fairly developed cognitive ability, he struggled to socialized.

    The process of linkage analysis could provide scientists with the information that they need in order to help the family. Interestingly, they discovered that the genes that indiciate the presence of Asperger loci overlaps with the loci reported earlier for autism and schizophrenia. The uniqueness of an affected individual's genome can provide immense amount of information and a diagnosis of the child may be made earlier on before the symptoms of the syndrome begin to develop. Similar to this research, the paper that I had read also amplifies the significane of gene positioning, with reference to its position in the nucleus. It was found that in individuals who have breast cancer had a specific alteration in a single gene. By knowing that the position of a gene is significant in a disorder or an illness can greatly contribute to the diagnosis of the disease. The importance of a gene's position implies that these genomic regions deserve additional analyses in clinical studies.

    ReplyDelete
  2. Your blog was very clear and easy to understand. I learned that Asperger’s, like Alzheimer’s, is associated with susceptibility loci in genes. In the case of Alzheimer’s, epigenetics were found to be involved in whether or not the person developed the disease, so I couldn’t help but wonder whether it is the same case with Asperger’s syndrome. That is, Alzheimer’s can be affected by external factors such as pesticide exposure, which expresses itself in terms of epigenetic modifications (variations in DNA methylation). Asperger’s is also affected by external factors, which include, as you wrote in your blog, infectious disease, heavy metal toxicity, certain vaccinations, perinatal factors, and even something as mundane as stress! Therefore, I think it would be worth investigating in the future whether epigenetic modification plays a role in the translation of these environmental factors into physical responses in Asperger’s, like it does in Alzheimer’s.

    Another thing I found interesting was that AS loci overlap some susceptibility loci for autism and schizophrenia. Although it seems reasonable that the susceptibility loci for autism and Asperger’s overlap, as they are quite similar with regards to the characteristics that they are associated with, schizophrenia, which results in hallucinations and a “breakdown of mental processes” rather than difficulty communicating or empathizing with other people, seems quite different from the other two disorders (not to mention Asperger’s and autism occur early on in a person’s life, whereas schizophrenia tends to manifest later on in a person’s lifetime—in their young adult years). Perhaps this shows that the three diseases have more in common than we know, and, in putting this information to use, could mean that a single drug or treatment could be developed to treat all three disorders. This area of research has yet to be fully developed, and I think, as we uncover more and more about these disorders, we might be able to get rid of them entirely. The more I read about these various disorders and the research done on them, the more I believe truly wondrous advances can be made in the medical field, changing the human quality of life for the better. Just 10 years ago we didn’t know epigenetics played a role in causing Alzheimer’s, or that Asperger’s syndrome had susceptibility loci that overlapped with those for autism and schizophrenia. I can’t even imagine where we’ll be 10 years from now!

    ReplyDelete