An examination of the relationship between hotspots and recombination associated with chromosome 21 nondisjunction

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, increas...

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Bibliographic Details
Published in:PloS one 2014-06, Vol.9 (6), p.e99560
Main Authors: Oliver, Tiffany Renee, Middlebrooks, Candace D, Tinker, Stuart W, Allen, Emily Graves, Bean, Lora J H, Begum, Ferdouse, Feingold, Eleanor, Chowdhury, Reshmi, Cheung, Vivian, Sherman, Stephanie L
Format: Article
Language:English
Subjects:
Age
Biology and life sciences
Chromosome 21
Chromosomes
Chromosomes, Human, Pair 21 - genetics
CpG islands
Down syndrome
Down Syndrome - genetics
Down's syndrome
Female
Genetic aspects
Genetic recombination
Genomes
Genomics
Genotype
Hot spots
Humans
Infants
Male
Medicine
Medicine and Health Sciences
Meiosis
Nondisjunction
Nondisjunction, Genetic
Oocytes
Oral hygiene
Placement
Polyadenine
Public health
Recombination
Recombination, Genetic
Risk analysis
Risk Factors
Statistical analysis
Studies
Trisomy
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0099560