Variation in the Zinc Finger of PRDM9 is Associated with the Absence of Recombination along Nondisjoined Chromosomes 21 of Maternal Origin

Oliver, Tiffany Renee, Spelman College
Harden, Ariel, Spelman College
Scott, Nyeisha, Spelman College
Johnson, Blair, Spelman College
Jones, Jillian, Spelman College
Walker, Christin, Spelman College
Wilkerso, Corinthia, Spelman College
Akinseye, Abisola, Spelman College
Middlebrooks, Candace, Laboratory of Translational Genomics
Smith, Tunde, Morehouse College
Feingold, Eleanor, University of Pittsburgh Graduate School of Public Health
Sherman, Stephanie L., Emory University School of Medicine

2016

2010-2019

Variation in the zinc finger-binding domain (ZFBD) of the protein PR Domain-Containing Protein 9 (PRDM9) is associated with altered placement of recombination in the human genome. As both the absence and altered placement of recombination are observed among chromosomes 21 that nondisjoin, we genotyped the PRDM9 ZFBD among mothers of children with Trisomy 21 in efforts to determine if variation within this region is associated with the recombination-related risk for chromosome 21 nondisjunction (NDJ). In our approach, PCR was used to amplify the ZFBD of PRDM9 and products were then subjected to bi-directional Sanger sequencing. DNA sequencing reads were aligned and compared to the sequence of the PRDM9 alleles previously identified. Chi-Square analysis was used to compare allele frequencies between cases (N=235, mothers of children with maternally-derived Trisomy 21) and controls (N=48, fathers of children with maternally-derived Trisomy 21). Results of our analysis showed that the frequency of PRDM9 ZF minor alleles is significantly increased among women displaying NDJ of chromosome 21 and no recombination on 21q (p=0.02). Even more, when compared to those for the PRDM9 major A-allele, these minor alleles displayed fewer predicted binding sites on 21q. These findings suggest that allelic variation in the ZF of PRDM9 may play a role in the risk for chromosome 21 NDJ by leading to reduced recombination on 21q. KEYWORDS: Nondisjunction; PRDM9; Recombination; Down syndrome; Zinc finger; Aneuploidy

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J Down Syndr Chr Abnorm, an open access journal Volume 2 Issue 2

Department of Biology, Division of Cancer Epidemiology and Genetics,Department of Human Genetics, Department of Bio statistics,

10.4172/2472-1115.1000115

http://hdl.handle.net/20.500.12322/sc.fac.pubs:2016_oliver_tiffany_r

http://rightsstatements.org/vocab/InC/1.0/