Asymmetry in Family History Implicates Nonstandard Genetic Mechanisms: Application to the Genetics of Breast Cancer


Genetic studies often collect family histories from diagnosed individuals. Some diseases exhibit inter-lineage asymmetry: mothers and their progenitors have higher (or lower) risk than fathers and their progenitors, and descendants of female cases have higher (or lower) risk than descendants of male cases. We describe how certain non-standard genetic mechanisms might underlie that asymmetry and make substantial contributions to disease susceptibility. Besides variants on sex chromosomes, these mechanisms include variants in the mother's genome that influence fetal development and hence later risk, variants in the mitochondria that modulate risk, and susceptibility variants in particular inherited genes whose expression depends on whether the variant came from the mother or the father. Applying our ideas to a study of more than 30,000 families with breast cancer, we found that more maternal grandmothers of cases than paternal grandmothers of cases had breast cancer, giving evidence that such non-standard mechanisms may be important contributors to breast cancer risk.


Vyšlo v časopise: Asymmetry in Family History Implicates Nonstandard Genetic Mechanisms: Application to the Genetics of Breast Cancer. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004174
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004174

Souhrn

Genetic studies often collect family histories from diagnosed individuals. Some diseases exhibit inter-lineage asymmetry: mothers and their progenitors have higher (or lower) risk than fathers and their progenitors, and descendants of female cases have higher (or lower) risk than descendants of male cases. We describe how certain non-standard genetic mechanisms might underlie that asymmetry and make substantial contributions to disease susceptibility. Besides variants on sex chromosomes, these mechanisms include variants in the mother's genome that influence fetal development and hence later risk, variants in the mitochondria that modulate risk, and susceptibility variants in particular inherited genes whose expression depends on whether the variant came from the mother or the father. Applying our ideas to a study of more than 30,000 families with breast cancer, we found that more maternal grandmothers of cases than paternal grandmothers of cases had breast cancer, giving evidence that such non-standard mechanisms may be important contributors to breast cancer risk.


Zdroje

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Genetika Reprodukčná medicína

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