The Association of rs1670533 Polymorphism in RNF212 Gene With the Risk of Down Syndrome in Young Women
AbstractObjective: To evaluate association between polymorphism rs1670533 in RNF212 gene with the risk of Down syndrome in young women.Materials and methods: In a case control study, one hundred pregnant women were evaluated in both group. The case group consisted pregnancy with diagnosis of Down syndrome in women younger than 35 years old. The control group consisted pregnancy with normal neonate. Fifty pregnant women in each group were allocated.one hundred blood samples were collected. Genomic DNA was extracted by salting – out method and polymorphism of rs1670533 were detected by PCR.PCR products were detected on 2% agarose gel electrophoresis.Results: The TTrs1670533 haplotype was present in 36% of pregnant women with Down syndrome versus 14% of normal pregnant women, (p = 0.003 e-12; CI 95%1.665-5.305, OR = 3.107); TC haplotype was present in 56% of normal pregnancy regarding of16% of pregnancy with Down syndrome (p = 4.288 e = 12; CI 95%: 0.145-0.25; OR = 0.126).Conclusion: It seems that TTrs1670533 haplotype is a risk factor for pregnancy with Down syndrome in young women and TC haplotype has protective effect.
Broman KW, Murray JC, Sheffield VC, White RL, Weber JL. Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am J Hum Genet 1998; 63:861-9.
Cheung VG, Burdick JT, Hirschmann D, Morley M. Polymorphic variation in human meiotic recombination. Am J Hum Genet 2007; 80:526-30.
Coop G, Wen X, Ober C, Pritchard JK, Przeworski M. High-resolution mapping of crossovers reveals extensive variation in fine-scale recombination patterns among humans. Science 2008; 319: 1395–8.
Shifman S, Bell JT, Copley RR, Taylor MS, Williams RW, Mott R, et al. Ahigh-resolution single nucleotide polymorphism genetic map of the mouse genome. PLoSBiol 2006; 4:e395.
Petkov PM, Broman KW, Szatkiewicz JP, Paigen K. Crossover interference underlies sex differences in recombination rates. Trends Genet 2007; 23: 539–42.
Hassold T, Hall H, Hunt P. The origin of human aneuploidy: where wehave been, where we are going. Hum Mol Genet 2007; 16, Spec No. 2: R203–8.
Lamb NE, Sherman SL, HassoldTJ. Effect of meiotic recombination onthe production of aneuploid gametes in humans. Cytogenet Genome Res 2005; 111: 250–5.
Henderson KA, Kee K, Maleki S, Santini PA, Keeney S. Cyclin –dependent kinase directly regulates initiation of meiotic recombination. Cell 2006; 125: 1321–32.
Keeney S, Neale MJ. Initiation of meiotic recombination by formation of DNA double-strand breaks: mechanism and regulation. BiochemSoc Trans2006; 34: 523–5.
Stahl FW, Foss HM. On Spo16 and the coefficient of coincidence.Genetics; 2009, 181: 327–30.
Stefansson H, Helgason A, Thorleifsson G, Steinthorsdottir V, Masson G, Barnard J, et al. A common inversion under selection in Europeans. Nat Genet; 2005; 37:129–137.
Kong A, Thorleifsson G, Stefansson H, Masson G, Helgason A, Gudbjartsson DF, et al. Sequence variants in the RNF212 gene associate with genome-wide recombinationrate. Science 2008; 319: 1398–401.
Weiss LA, Shen Y, Korn JM, Arking DE, Miller DT, Fossdal R, et al. Association between microdeletion and microduplication at 16p11.2 and autism. NEngl J Med 2008; 358: 667–75.
Dawber TR, Meadors GF, Moore FE Jr. Epidemiological approaches to heart disease: the Framingham Study. Am J Public Health Nations Health 1975; 41:279–81.
Kong A, Gudbjartsson DF, Sainz J, Jonsdottir GM, Gudjonsson SA, ichardsson B, et al. A high-resolution recombination map of the human genome. Nature Genetics2002; 31: 241–7.
Sadiq MF, Al-Refai EA, Al-Nasser A, Khassawneh M, Al-Batayneh Q. Methylenetetrahydrofolate reductase polymorphisms C677T and A1298C as maternal risk factors for Down syndrome in Jordan. Genet Test Mol Biomarkers. 2011; 15:51-7.
Barrett T, Troup DB, Wilhite SE, Ledoux P, Rudnev D, Evangelista C, et al. NCBIGEO: mining tens of millions of expression profiles–database and tools update. Nucleic Acids Res2007; 35: D760–5.
Lamprecht G, SeidlerU. The emerging role of PDZ adapter proteins forregulation of intestinal ion transport. Am J PhysiolGastrointest LiverPhysiol 2006; 291: G766–77.
Lassalle B, Bastos H, Louis JP, Riou L, Testart J, Dutrillaux B, et al. ‘Side Population’cells in adult mouse testis express Bcrp1 gene and are enriched in spermatogoniaand germinal stem cells. Development 2004; 131: 479–87.
Bastos H, Lassalle B, Chicheportiche A, Riou L, Testart J, Allemand I, et al. Flowcytometric characterization of viable meiotic and postmeiotic cells by Hoechst33342 in mouse spermatogenesis. Cytometry A2005; 65: 40–9.
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, et al. PLINK: a tool set for whole-genome association and population-based linkageanalyses. Am J Hum Genet 2007; 81: 559–75.
Li Y, Abecasis GR. Mach 1.0: Rapid haplotype reconstruction andmissing genotype inference. Am J Hum Genet2006; S79: 2290.
Brick K, Smagulova F, Khil P, Camerini-Otero RD, Petukhova GV. Genetic recombination is directed away from functional genomic elements in mice. Nature 2012; 485:642–5.
24. Grey C, Barthès P, Chauveau-Le Friec G, Langa F, Baudat F, de Massy B. Mouse PRDM9 DNA-binding specificity determines sites of histone H3 lysine 4 trimethylation for initiation of meiotic recombination. PLoSBiol 2011; 9:e1001176.
Baudat F, Buard J, Grey C, Fledel-Alon A, Ober C, Przeworski M, et al. PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science 2010;327:836–40.