Support for 'Disease-Only' Genotypes and Excess of Homozygosity at the CYTH4 Primate-Specific GTTT-Repeat in Schizophrenia
| Autor: | Shaghyegh Taghavi, Simin Rahimi-Aliabadi, Haleh Akhavan-Niaki, Neda Shahmohammadibeni, Javad Jamshidi, Ramin Pouriran, Farhad Ramezani Nejad, Ehteram Khademi, Parasto Shokraeian, Elham Alehabib, Coro Paisán-Ruiz, Ehsan Esmaili Shandiz, Mina Ohadi, Monavvar Andarva, Nader Mansoori, Azadeh Ahmadifard, Hossein Darvish |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Iran Biology Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Polymorphism (computer science) Gene expression Genotype Guanine Nucleotide Exchange Factors Humans SNP Allele Promoter Regions Genetic Gene Alleles Genetic Association Studies Genetics (clinical) Genetics Promoter General Medicine Middle Aged humanities 030104 developmental biology Case-Control Studies Schizophrenia Microsatellite Female Cell Adhesion Molecules 030217 neurology & neurosurgery Microsatellite Repeats |
| Zdroj: | Genetic Testing and Molecular Biomarkers. 21:485-490 |
| ISSN: | 1945-0257 1945-0265 |
| DOI: | 10.1089/gtmb.2016.0422 |
| Popis: | 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.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.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 exact0.007). The frequency of the 11-repeat allele was estimated at 0.02 and 0.006 in the SCZ patients and controls, respectively (Mid p exact0.006).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. |
| Databáze: | OpenAIRE |
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