Ehteram Khademi1, Elham Alehabib2, Ehsan Esmaili Shandiz3, Azadeh Ahmadifard2, Monavvar Andarva2, Javad Jamshidi4, Simin Rahimi-Aliabadi2, Ramin Pouriran2, Farhad Ramezani Nejad5, Nader Mansoori5, Neda Shahmohammadibeni1, Shaghyegh Taghavi2, Parasto Shokraeian6, Haleh Akhavan-Niaki1, Coro Paisán-Ruiz7,8,9, Hossein Darvish1,2, Mina Ohadi10. 1. 1 Cellular and Molecular Biology Research Center, Babol University of Medical Sciences , Babol, Iran . 2. 2 Department of Medical Genetics, Shahid Beheshti University of Medical Sciences , Tehran, Iran . 3. 3 Department of Neurology, Ganjavian Hospital, Dezful University of Medical Sciences , Dezful, Iran . 4. 4 Noncommunicable Diseases Research Center, Fasa University of Medical Sciences , Fasa, Iran . 5. 5 The Charitable Institute for Protecting of Social Victims (Saray-e-Ehsan) , Tehran, Iran . 6. 6 Tehran Medical Sciences Branch, Islamic Azad University , Tehran, Iran . 7. 7 Departments of Neurology, Psychiatry and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai , New York, New York. 8. 8 Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai , New York, New York. 9. 9 Friedman Brain Institute , Icahn School of Medicine at Mount Sinai, New York, New York. 10. 10 Iranian Research Center on Aging, University of Social Welfare and Rehabilitation Sciences , Tehran, Iran .
Abstract
OBJECTIVE: The role of short tandem repeats (STRs) in the control of gene expression among species is being increasingly understood following the identification of several instances in which certain STRs occur identically, or expand differentially, in primates versus nonprimates. These STRs may regulate genes that participate in characteristics that are associated with the divergence of primates from sibling orders (e.g., brain higher order functions). The CYTH4 gene contains the longest tetranucleotide STR in its core promoter, at 7-repeats, and links to the evolution of human and nonhuman primates. Allele and genotype distribution of this STR were studied in patients affected by schizophrenia (SCZ) and controls. METHODS: High-resolution data were obtained on the allele and genotype distribution of the CYTH4 STR and a novel C > T single-nucleotide polymorphism (SNP) at its immediate upstream sequence in 255 patients with SCZ and 249 controls. Each sample was sequenced twice using the fluorescent dye termination method. RESULTS: Novel alleles were detected at the long extreme of the GTTT-repeat, at 10- and 11-repeats, in the SCZ cases and controls. Excess of homozygosity was observed for the entire range of alleles across the GTTT-repeat and the C > T SNP in the SCZ patients in comparison with the controls (Yates corrected p < 0.011). Three genotypes consisting of the 11-repeat allele (i.e., 11/11, 10/11, and 7/11) were detected only in the SCZ patients (i.e., disease-only genotypes), and contributed to 2.3% of the SCZ genotypes (Mid p exact <0.007). The frequency of the 11-repeat allele was estimated at 0.02 and 0.006 in the SCZ patients and controls, respectively (Mid p exact <0.006). CONCLUSION: This indicates that STR genotypes that are absent in the control group may be risk factors for SCZ. Future studies are warranted to test the significance of our findings.
OBJECTIVE: The role of short tandem repeats (STRs) in the control of gene expression among species is being increasingly understood following the identification of several instances in which certain STRs occur identically, or expand differentially, in primates versus nonprimates. These STRs may regulate genes that participate in characteristics that are associated with the divergence of primates from sibling orders (e.g., brain higher order functions). The CYTH4 gene contains the longest tetranucleotide STR in its core promoter, at 7-repeats, and links to the evolution of human and nonhuman primates. Allele and genotype distribution of this STR were studied in patients affected by schizophrenia (SCZ) and controls. METHODS: High-resolution data were obtained on the allele and genotype distribution of the CYTH4 STR and a novel C > T single-nucleotide polymorphism (SNP) at its immediate upstream sequence in 255 patients with SCZ and 249 controls. Each sample was sequenced twice using the fluorescent dye termination method. RESULTS: Novel alleles were detected at the long extreme of the GTTT-repeat, at 10- and 11-repeats, in the SCZ cases and controls. Excess of homozygosity was observed for the entire range of alleles across the GTTT-repeat and the C > T SNP in the SCZ patients in comparison with the controls (Yates corrected p < 0.011). Three genotypes consisting of the 11-repeat allele (i.e., 11/11, 10/11, and 7/11) were detected only in the SCZ patients (i.e., disease-only genotypes), and contributed to 2.3% of the SCZ genotypes (Mid p exact <0.007). The frequency of the 11-repeat allele was estimated at 0.02 and 0.006 in the SCZ patients and controls, respectively (Mid p exact <0.006). CONCLUSION: This indicates that STR genotypes that are absent in the control group may be risk factors for SCZ. Future studies are warranted to test the significance of our findings.
Entities:
Keywords:
CYTH4; exceptionally long; primate-specific; schizophrenia; short tandem repeat
Authors: H Afshar; S Khamse; F Alizadeh; A Delbari; R Najafipour; A Bozorgmehr; M Khazaei; F Adelirad; A Alizadeh; A Kowsari; M Ohadi Journal: Sci Rep Date: 2020-11-10 Impact factor: 4.379