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Evolving evidence on a link between the ZMYM3 exceptionally long GA-STR and human cognition

Afshar, H. and Khamse, S. and Alizadeh, F. and Delbari, A. and Najafipour, R. and Bozorgmehr, A. and Khazaei, M. and Adelirad, F. and Alizadeh, A. and Kowsari, A. and Ohadi, M. (2020) Evolving evidence on a link between the ZMYM3 exceptionally long GA-STR and human cognition. Scientific Reports, 10 (1).

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Abstract

The human X-linked zinc finger MYM-type protein 3 (ZMYM3) contains the longest GA-STR identified across protein-coding gene 5� UTR sequences, at 32-repeats. This exceptionally long GA-STR is located at a complex string of GA-STRs with a human-specific formula across the complex as follows: (GA)8-(GA)4-(GA)6-(GA)32 (ZMYM3-207 ENST00000373998.5). ZMYM3 was previously reported among the top three genes involved in the progression of late-onset Alzheimer�s disease. Here we sequenced the ZMYM3 GA-STR complex in 750 human male subjects, consisting of late-onset neurocognitive disorder (NCD) as a clinical entity (n = 268) and matched controls (n = 482). We detected strict monomorphism of the GA-STR complex, except of the exceptionally long STR, which was architecturally skewed in respect of allele distribution between the NCD cases and controls F (1, 50) = 12.283; p = 0.001. Moreover, extreme alleles of this STR at 17, 20, 42, and 43 repeats were detected in seven NCD patients and not in the control group (Mid-P exact = 0.0003). A number of these alleles overlapped with alleles previously found in schizophrenia and bipolar disorder patients. In conclusion, we propose selective advantage for the exceptional length of the ZMYM3 GA-STR in human, and its link to a spectrum of diseases in which major cognition impairment is a predominant phenotype. © 2020, The Author(s).

Item Type: Article
Additional Information: cited By 0
Subjects: روانپزشکی WM
سیستم عصبی WL
آسیب شناسی QZ
مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 16 Nov 2020 07:56
Last Modified: 16 Nov 2020 07:56
URI: http://eprints.goums.ac.ir/id/eprint/10861

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