EPHA1 gene SNPs analysis in population of Ukraine

Gulkovskyi, R. V.; Chernushyn, S. Yu.; Kravchenko, S. A.; Bychkova, G. M.; Лившиц, Л. А.

doi:10.7124/bc.000841

Cited by 3 publications

(3 citation statements)

References 14 publications

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“…The TruA family includes Pus1 from E. coli (also called truA or hisT) which modifi es positions 38, 39, and 40 in the ASL of bacterial tRNAs [18]. Other members are Pus3 from mouse [1]; Pus3 from yeast (also known as Deg1) -modifi es positions 38 and 39 [14] and human mitochondrial Pus1 modifi es positions 27, 28, 34, and 36 in tRNAs in vitro and in vivo [19,20]. The atomic models for various members of the PUS families (TruA, TruB, TruD, RluA, RsuA, and Pus10) have been solved and have shown a conserved catalytic core that presents a high degree of structural similarity and is the most stable region of the protein.…”

Section: Resultsmentioning

confidence: 99%

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Novel gene PUS3 c.A212G mutation in Ukrainian family with intellectual disability

2015

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To evaluate a possible role of a novel c.A212G substitution in the PUS3 gene at intellectual disability (ID). Methods. The observed group consisted of the ID Ukrainian family members (parents and two affected children) and the control group-of 300 healthy individuals from general population of Ukraine. Sanger sequencing of the PUS3 gene exon 1 was performed for the family members. Polymorphic variants of c.A212G were analyzed using ARMS PCR. The homology models of wild type and p.Y71C mutant catalytic domains of human Pus3 were generated using the crystal structure of the human Pus1 catalytic domain (PDB ID: 4NZ6) as a template. Results. It was shown that the father of the affected siblings was the c.A212G substitution heterozygous carrier whereas the mother was a wild type allele homozygote, and the exom sequencing result was confi rmed-the affected children are 212G homozygotes. We supposed de novo mutation in the maternal germ line. A low frequency of 212G allele (0.0017) was shown in the population of Ukraine. Homology modelling of the wild type and p.Y71C mutant catalytic domain of human Pus3 revealed that substitution p.Y71C is located in close proximity to its active site. Conclusions. The absence of hypoproteinemia in our patients, homozygous for the 212C allele allows us to assume that the mutation c.A212G PUS3 is rather neutral and cannot be the major cause of ID. However, considering a low frequency of the 212G allele in the population and close localization of p.Y71C substitution to the active site of hPus3 we cannot exclude that the c.A212G mutation in PUS3 may be a modifi er for some pathologies including syndromic ID.

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Section: Resultsmentioning

confidence: 99%

“…The exome analysis revealed several variants in either homozygous or compound heterozygous state in few genes: EPHA1 [1], PUS3 and ZNF527.…”

Section: Introductionmentioning

confidence: 99%

Novel gene PUS3 c.A212G mutation in Ukrainian family with intellectual disability

2015

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“…In recent reports we have presented our study on the whole exome sequencing (WES) in two affected siblings with non-syndromic intellectual disability from Ukrainian family and their healthy non-consanguineous parents that identifi ed two missense mutations in the coding region of the EPHA1 gene (c. 1475 G > A -rs11768549 and novel c.1891G > A) [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Association of the EPHA1 gene polymorphism with idiopathic mild intellectual disability

2015

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Aim.To investigate a possible association of the EPHA1 gene polymorphism with mild intellectual disability (ID). Methods. The group of patients with mild (IQ score between 50 and 70) idiopathic intellectual disability consisted of 65 individuals including 41 (63.1 %) males and 24 (36.9 %) females. The control group consisted of 250 healthy volunteers from different regions of Ukraine. The genotyping was performed using PCR followed by RFLP analysis for rs11768549, rs11767557, rs11771145 and ARMS PCR analysis for novel c.1891G>A EPHA1 gene mutation. Results. The data concerning the EPHA1 genotypes and allelic variants distribution in ID patients and control group were obtained. Statistical analysis showed a signifi cant association of minor rs11768549-A allele (OR = 3.96, 95 % CI = 1.13-13.89) and wild-type rs11767557-T (OR = 1.99, 95 % CI = 1.18-3.37) and rs11771145-G (OR= 1.55, 95 % CI = 1.02-2.37) alleles with a higher risk of mild ID development (p < 0.05 for all). Conclusions. Our results suggest that SNPs (rs11768549, rs11767557, rs11771145) in the EPHA1 gene are associated with idiopathic mild intellectual disability. Therefore, we propose the EPHA1gene as a new candidate gene and the polymorphisms rs11768549, rs11767557, rs11771145 as new markers of genetic susceptibility for intellectual disability. K e y w o r d s: EPHA1 gene, intellectual disability, polymorphism, genetic susceptibility.

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