ASD, or autism spectrum disorder is a group ofneurodevelopmental disorders, which is wide-spread in the world. Firstly, it is important to mention that ASD cannot be referred as a disease model, as it belongs to neurological diversity and cannot be cured [1]. Although it is possible to make the life of people with ASD better through therapy. This type of disorder has a great impact on the health of individuals who suffer from it. People, having ASD, experience many difficulties in their life and well-being depending on severity of their disorder.
The individuals with ASD show such symptoms as gaps in their socialization process, dysfunctions of verbal skills, and repetitive behavior [1]. In addition, intellectual disability, anxiety, and lack of movements control can be the characteristics of ASD [2].
Like other disorders, ASD has its set of factors which can influence the very occurrence of it and the individual differencesin phenotype (seen symptoms) of people who suffer from it. As ASD is a complex disorder, many factors, unrelated to each other, are able to cause ASD through a combinative way. That is, there are environmental factors, genetic factors, and other,unknown factors, which contribute to ASD’s occurrence [3]. In this article, we will focus on genetic factors of ASD.
Figure 1. ASD and genetics are related [1]
Genetic factors are the gene mutations and their results which play a big role in many biological pathways. Changes in chromosomes are represented by CNVs (copy number variations), SNV (single nucleotide variants), and LGD (likely gene disrupting) whose examples are chromosome mutations, like duplication, deletion, inversion, and translocation, and other examples [4]. Now, we will look at them more carefully:
CNVs are usually individual for each person with ASD, however, same CNVs can be seen in a few percent of them. CNVs most likely to affect organism not alone, but together – in a complex of CNVs. There are also de novo CNVs which are identified in the most likely mutated genes and the genes of synaptic functions in ASD case [2]. In a nervous system CNVs have an impact on synaptic transmission and they are bound to the fragile X syndrome (responsible for tribal intellectual disability, usually affecting males [1]). Also, as the CNV’s duplication rate increases, consequently, ASD’s severity rises. The rare-spread CNVs are in the charge of impairments in cell proliferation and chromatin regulation [4].
Mostly de novo SNVs of other SNVs contribute to ASD occurrence. Although they have a higher chance of being on paternal chromosome rather than maternal one, the following mutations – frameshift, missense, and stop-gain – have a higher rate in females than males [2].
Such mutations as frameshift, nonsense, and splice site, relate to LGD. Individuals with LGD types of mutations seem to have lower non-verbal IQ. LGD affects proteins which contribute to neuron development, signaling pathways work, and chromatin modeling process. Besides, a tendency of inherited maternal LGD is seen in sons [2].
mtDNA is an inherited type of information controlling metabolism processes in an organism. Mitochondria’s dysfunction is embodied in a such metabolic problems as enzyme absence, thus resulting in agglomeration of toxic substances being harmful for developing brain [1].
This type of mutation can be claimed as a genetic factor, because the mutated genes, being discovered in cerebellum, provide some coordination problems in an individual. Additionally, some variants of such mutation have an increased expression in amygdala, which results in degraded emotional responses and decreased social awareness. It happens due to SCN2A gene mutations influence on action potential in the neurons [4].
It includes gene transcription process. Following genes – MECP2, MEF2C, HDAC4, CHD8, CTNNB1 – are regulated by neurons activity, and have an impact on connection between the neurons and plasticity of the synapse [2].
Also is known as translation process. So called mTOR pathway regulates general mRNA translation in both directions, thus, being damaged, causes diseases originated from abnormal cell proliferation and ASD. Specifically, the FMRP–EIF4E–CYFIP1complex regulates mRNA translation at the synapse and of other genes associated with ASD. Errors result in the fragile X syndrome and raised ASD risk [2].
Protein degradation process is controlled by ubiquitin-proteasome system (UPS). If affecting UBE3A gene, which is responsible for a ubiquitin ligase, has the duplication pattern, it may indicate on ASD in the individuals.
Such functions as activity-driven synapse formation (neurexins and neuroligins), and cell-adhesion molecules and neurotransmitter receptors station (scaffolding proteins) might be damaged because of the duplication and deletion in the related genes (NRXN, NLGN, and SHANK genes) [2]. In addition, these genes’ abnormalities are suggested to be the most spread ones severely associated with ASD [3].
Overall, ASD is a serious and complex neurodevelopmentaldisorder which cannot be provoked by only one gene mutation. As we found, both inheritable and de novo mutations can be genetic factors of ASD in the progenies, despite of de novo ones’ inability of being passed down [2]. Also, ASD can strictly differ from one sibling to another one in spite of coming from the same family [4]. It means that there is a variety of genetic factors which contribute to ASD, and more genes that can be assumed as ASD risk genes.
Today’s findings are accepted as a relief for a psychiatric field and whole families in terms of understanding of condition of the individuals with ASD and learning how to contact with them. Therefore, the therapy approached on improving these individuals’ lives is to be updated. However, it is clear that future research on factors and reasons of ASD occurrence among people should be provided.
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