Inheritance of Susceptibility to Malignant Blood Disorders

Malignant blood disorders depend on heritable susceptibility genes and occur in familial aggregations. We suggest a model of transgenerational segregation of the susceptibility genes based on the study of malignant blood disorders in Norwegian and Danish families with unrelated parents, and in the i...

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Bibliographic Details
Published in:Scientific reports 2019-02, Vol.9 (1), p.2444-2444, Article 2444
Main Authors: Jønsson, Viggo, Awan, Haneef, Jones, Neil D., Johannesen, Tom B., Steig, Bjarni á, Andosdottir, Gudrid, Tjønnfjord, Geir E.
Format: Article
Language:English
Subjects:
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Blood
Blood diseases
Chimerism
Chronic lymphocytic leukemia
Genomic imprinting
Health risk assessment
Humanities and Social Sciences
Imprinting
Inbreeding
Leukemia
Lymphatic leukemia
Lymphoma
multidisciplinary
Multiple myeloma
Offspring
Science
Science (multidisciplinary)
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Summary:Malignant blood disorders depend on heritable susceptibility genes and occur in familial aggregations. We suggest a model of transgenerational segregation of the susceptibility genes based on the study of malignant blood disorders in Norwegian and Danish families with unrelated parents, and in the inbred Faroese population with related parents. This model, consisting of parental genomic imprinting and mother-son microchimerism, can explain the male predominance in most of the diseases, the predominance of affected parent-offspring when parents are not related, and the different modes of segregation in males and females. The model displays a specific pattern in the distribution of affected relatives for each diagnosis, viz. a characteristic distribution in the pedigrees of family members with malignant blood disorder related to the proband. Three such patterns, each reflecting a specific transgenerational passage, were identified: (1) alterations in the number of affected relatives in paternal lines alone, e.g. in patterns for probands with multiple myeloma; (2) alterations in the number of affected relatives in both paternal and maternal lines for probands with chronic lymphocytic leukemia; and (3) no alterations in the numbers of male and female affected relatives in the parental lines, e.g. for probands with some types of malignant lymphoma.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-38879-y