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, Z_max>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, Z_{max 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>.

Position Paper: con

            Golden Rice was meant to be launch on the market after over 10 years of research and development. Advocates maintain that there is no alternative to this genetically engineered rice variety in the fight against vitamin A deficiency and accuse government agencies and critics of endangering the lives of millions of children. Some even go as far as to charge government agencies and critics of being complicit in bringing about a “Holocaust.” To speed up market approval and limit expenses, they demand a general loosening of standards for the risk assessment of genetically engineered plants.

            However, this report shows that the managers of the Golden Rice project have demonstrated a disregard for necessary scientific accuracy and precision and thus I am against Golden Rice project. They have employed propagandistic methods to push the project beyond the issue of vitamin A deficiency, setting a precedent to increase the pressure on regulatory authorities and accelerate the introduction of agricultural biotechnology.

            It is still not possible to judge whether or not Golden Rice is even technically able to combat vitamin A deficiency. No data has been made available on the degradation rate of its B carotenoid content in our stomach during storage nor on its bioavailability. Any risks posed by the cultivation or consumption of Golden Rice has been largely ignored. Very little data is available on new active ingredients and changes in the metabolism of the plants, and on the reaction of the plants to changing environmental conditions. So far not a single feeding study on the rice has been published. In spite of all this, a trial has already been conducted on Chinese school children. This “experiment” on human alone is inhumane since golden rice can cause allergies from transferring genes from other species. A study has shown that putting a protein that kills pests into pea DNA and feeding that pea to mice have done this. It was found that the altered chemical structure of protein caused allergies in mice.

            It is highly likely that the commercial cultivation of Golden Rice will lead to the irreversible entry of this genetically engineered organism into the environment and to its crossbreeding with local rice varieties. It is not scientifically possible to predict the long term ecological consequences. Other than this, poor people have harder time to pay for the Golden Rice product. Therefore, I do not support the Golden Rice project.

           

In sickness and in health

This article stresses the importance of genetics in many diseases. For example, in cystic fibrosis, a single mutation in a single is enough to cause the disease. Other examples derive from a subtler cause, such as diabetes and asthma, which are caused by our slight and subtle genetic influence. Our class just took a test on DNA transcription, translation, and an introduction to genetics. In the latter, we explore the basis of genetic mutation, particularly base substitution mutation. This topic ties back to the article when it mentions a disorder that affects the blood’s oxygen carrying protein hemoglobin. According to the topic we’re learning, the disorder that derives from the base substitution mutation that affects the hemoglobin’s shape is known as sickle cell anemia since its shape looks like a sickle cell and thus has a harder time carrying oxygen throughout the entire body.