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Risk of Down syndrome birth: Consanguineous marriage is associated with maternal meiosis‐II nondisjunction at younger age and without any detectable recombination error
Author(s) -
Ray Anirban,
Oliver Tiffany Rene,
Halder Pinku,
Pal Upamanyu,
Sarkar Sumantra,
Dutta Supratim,
Ghosh Sujay
Publication year - 2018
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.40511
Subject(s) - nondisjunction , meiosis ii , meiosis , consanguinity , genetics , consanguineous marriage , chromosome 21 , biology , trisomy , aneuploidy , chromosome , gene
Consanguineous marriage was examined as a risk factor for Down syndrome birth. We genotyped Down syndrome family trios using short tandem repeat markers on 21q‐to interpret the parental and meiotic stage of origin of errors as well as to record recombination profile along long arm of chromosome 21. We then compared nonconsanguineous (N = 811) group with‐the consanguineous (N =157) marriages. We report for the first time that consanguineous marriage is associated with an increased risk for nondisjunction of chromosome 21 in oocytes‐during the second meiotic division. We observed the absence of recombination more frequently in younger mothers in nonconsanguineous meiosis I cases. This was in contrast to an equal distribution of nonrecombinant cases across the age categories in the meiosis I consanguineous group. Moreover, the non‐consanguineous group exhibited preferential telomeric recombination in meiosis I error among younger women and centromeric recombination in meiosis II errors in older women. In contrast, the consanguineous group exhibited medially placed recombination events in both meiosis I and meiosis II nondisjunction errors. Additionally, we recorded reduced maternal age at conception in the‐consanguineous group. These findings suggest novel risk factors associated that increase the risk of chromosome 21 nondisjunction in the families with consanguinity.