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Gene Reports
journal homepage: www.elsevier.com/locate/genrep
Association analysis of highly accelerated region 1A variant and risk of
psychiatric conditions
Amir Namvar
a,1
, Mohammad Taheri
b,1
, Mir Salar Kahaei
a
, Mir Davood Omrani
a
, Farah Moayedi
c
,
Arezou Sayad
a,
⁎
, Soudeh Ghafouri-Fard
a,
⁎
a
Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
b
Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
c
Department of Psychiatry, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
ARTICLEINFO
Keywords:
Highly accelerated region 1A
HAR1A
rs750697
Substance abuse
ADHD
Bipolar disorder
Major depressive disorder, schizophrenia
ABSTRACT
Long non-coding RNAs (lncRNAs) participate in the neurodevelopment and species divergence. They also
contribute in the etiology of neuropsychiatric disorders. The highly accelerated region 1a (HAR1A) lncRNA is
regarded as one of the features of the evolutionary deviation of humans and chimpanzees and participates in
specification and migration of neuron especially in cortex. In the current study, we genotyped a single nucleotide
polymorphism (SNP) in this lncRNA (rs750697) in a population of Iranian patients with different neu-
ropsychiatric conditions such as substance addiction, attention deficit hyperactive disorder, bipolar disorder,
major depressive disorder and schizophrenia. There was no significant difference between allele and genotype
frequencies of this SNP between any subgroup of patients and the corresponding age- and sex-matched controls.
Consequently, the current study excludes the participation of the rs750697 SNP in the etiology of neu-
ropsychiatric disorders in Iranian population. Further assessment of other SNPs within this lncRNA might lead to
identification of possible risk factors for neuropsychiatric disorders.
1. Introduction
Several studies have demonstrated expression of long noncoding
RNAs (lncRNAs) in neurons both in early stages of neuron specification
and in mature brain tissues (Levchenko et al., 2018). Abnormal lncRNA
signature has been linked with a variety of neuropsychiatric conditions.
The critical roles of some lncRNAs in neurodevelopment and neuron
activities have been recognized (Levchenko et al., 2018). The highly
accelerated region 1a (HAR1A) lncRNA is regarded as one of the features
of the evolutionary deviation of humans and chimpanzees and parti-
cipates in the specification and migration of neurons especially in the
cortex (Tolosa et al., 2008). This lncRNA is among the first recognized
human accelerated regions (HARs). These regions are among the most
remarkable sequences in the human genome in the divergence of Homo
sapiens species, particularly regarding the extraordinarily advanced
features of human brain (Levchenko et al., 2018). During the process of
neocortex evolution in human, HAR1A has been demonstrated to be
expressed in Cajal–Retzius neurons, along with reelin (Pollard et al.,
2006a). Expression of HAR1A has been detected in the evolving human
brain during the period of 7–18 weeks of pregnancy age when it is
expressed in the dorsal telencephalon. Notably, the whole cerebellum
and forebrain of adult brain express this lncRNA (Pollard et al., 2006b).
Suppression of HAR1 expression by the master transcriptional repressor
REST is possibly implicated in the pathogenesis of neurodegeneration in
the context of Huntington's disease (Pollard et al., 2006b).
HAR1A has a single nucleotide polymorphism (SNP) (rs750697)
https://doi.org/10.1016/j.genrep.2019.100489
Received 8 August 2019; Received in revised form 17 August 2019; Accepted 19 August 2019
Abbreviations: lncRNAs, Long non-coding RNAs; HAR1A, highly accelerated region 1a; SNP, single nucleotide polymorphism; HARs, human accelerated regions;
ADHD, attention deficit hyperactive disorder; BP, bipolar disorder; MDD, major depressive disorder; SCZ, schizophrenia; ARMS, tetra-primer amplification-refractory
mutation system; DSM-V, Diagnostic and Statistical Manual of Mental Disorders; HWE, Hardy-Weinberg equilibrium
⁎
Corresponding authors.
E-mail addresses: ar.sayad@sbmu.ac.ir (A. Sayad), s.ghafourifard@sbmu.ac.ir (S. Ghafouri-Fard).
1
The first two authors contributed equally.
Gene Reports 17 (2019) 100489
Available online 28 August 2019
2452-0144/ © 2019 Elsevier Inc. All rights reserved.
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