title: An examination of the relationship between hotspots and recombination associated with chromosome 21 nondisjunction.
abstract: Trisomy 21, resulting in Down Syndrome (DS), is the most common autosomal trisomy among live-born infants and is caused mainly by nondisjunction of chromosome 21 within oocytes. Risk factors for nondisjunction depend on the parental origin and type of meiotic error. For errors in the oocyte, increased maternal age and altered patterns of recombination are highly associated with nondisjunction. Studies of normal meiotic events in humans have shown that recombination clusters in regions referred to as hotspots. In addition, GC content, CpG fraction, Poly(A)/Poly(T) fraction and gene density have been found to be significant predictors of the placement of sex-averaged recombination in the human genome. These observations led us to ask whether the altered patterns of recombination associated with maternal nondisjunction of chromosome 21 could be explained by differences in the relationship between recombination placement and recombination-related genomic features (i.e., GC content, CpG fraction, Poly(A)/Poly(T) fraction or gene density) on 21q or differential hot-spot usage along the nondisjoined chromosome 21. We found several significant associations between our genomic features of interest and recombination, interestingly, these results were not consistent among recombination types (single and double proximal or distal events). We also found statistically significant relationships between the frequency of hotspots and the distribution of recombination along nondisjoined chromosomes. Collectively, these findings suggest that factors that affect the accessibility of a specific chromosome region to recombination may be altered in at least a proportion of oocytes with MI and MII errors.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America; Department of Biology, Spelman College, Atlanta, Georgia, United States of America.
authors.forename: Tiffany Renee
authors.initials: TR
authors.lastname: Oliver
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Candace D
authors.initials: CD
authors.lastname: Middlebrooks
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Tinker
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Emily Graves
authors.initials: EG
authors.lastname: Allen
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Lora J H
authors.initials: LJ
authors.lastname: Bean
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Ferdouse
authors.initials: F
authors.lastname: Begum
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Human Genetics, Graduate School of Public Health University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Feingold
authors.affiliation: Department of Human Genetics, Graduate School of Public Health University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Reshmi
authors.initials: R
authors.lastname: Chowdhury
authors.affiliation: Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, United States of America; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Vivian
authors.initials: V
authors.lastname: Cheung
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Sherman
mesh_terms: D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004314:Down Syndrome / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008540:Meiosis; D009630:Nondisjunction, Genetic; D011995:Recombination, Genetic; D012307:Risk Factors