Meiotic drive in chronic lymphocytic leukemia compared with other malignant blood disorders

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  • Viggo Jønsson
  • Haneef Awan
  • Neil Deaton Jones
  • Tom Børge Johannesen
  • Klaus Thøgersen
  • Bjarni Steig
  • Gudrid Andorsdottir
  • Geir Erland Tjønnfjord

The heredity of the malignant blood disorders, leukemias, lymphomas and myeloma, has so far been largely unknown. The present study comprises genealogical investigations of one hundred and twelve Scandinavian families with unrelated parents and two or more cases of malignant blood disease. For comparison, one large family with related family members and three hundred and forty-one cases of malignant blood disease from the Faroese population was included. The inheritance is non-Mendelian, a combination of genomic parental imprinting and feto-maternal microchimerism. There is significantly more segregation in maternal than in paternal lines, predominance of mother-daughter combinations in maternal lines, and father-son combinations in paternal lines. Chronic lymphocytic leukemia is the most frequent diagnosis in the family material, and chronic lymphocytic leukemia has a transgenerational segregation that is unique in that inheritance of susceptibility to chronic lymphocytic leukemia is predominant in males of paternal lines. Male offspring with chronic lymphocytic leukemia in paternal lines have a birth-order effect, which is manifest by the fact that there are significantly more male patients late in the sibling line. In addition, there is contravariation in chronic lymphocytic leukemia, i.e. lower occurrence than expected in relation to other diagnoses, interpreted in such a way that chronic lymphocytic leukemia remains isolated in the pedigree in relation to other diagnoses of malignant blood disease. Another non-Mendelian function appears in the form of anticipation, i.e. increased intensity of malignancy down through the generations and a lower age at onset of disease than otherwise seen in cases from the Cancer Registers, in acute lymphoblastic leukemia, for example. It is discussed that this non-Mendelian segregation seems to spread the susceptibility genes depending on the gender of the parents and not equally to all children in the sibling line, with some remaining unaffected by susceptibility i.e. "healthy and unaffected", due to a birth order effect. In addition, anticipation is regarded as a non-Mendelian mechanism that can amplify, «preserve» these vital susceptibility genes in the family. Perhaps this segregation also results in a sorting of the susceptibility, as the percentage of follicular lymphoma and diffuse large B-cell lymphoma is lower in the family material than in an unselected material. Although leukemias, lymphomas and myelomas are potentially fatal diseases, this non-Mendelian distribution and amplification hardly play any quantitative role in the survival of Homo sapiens, because these diseases mostly occur after fertile age.

OriginalsprogEngelsk
Artikelnummer6138
TidsskriftScientific Reports
Vol/bind12
Udgave nummer1
Sider (fra-til)1-11
ISSN2045-2322
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
We want to thank the Genetic Resource Centre, Ministry of Health and Social Service, Government of the Faroe Islands, Eirargardur 2, FO-100 Torshavn, Faroe Islands, for permission to do the study and for the access to data from the Faroe Islands (record no. July 18 and October 12, 2007). Special thanks to Mr. Hans Pauli Str?m, former Minister of Social Affairs and Health, Torshavn, for valuable information about the Faroese population. For permission to undertake the study in Norway, we thank the Norwegian Research Ethical Committees, Kongens gata 14, NO-0153 Oslo, Norway, that includes the Data Inspectorate (record no. 07/00254-2), the Social and Health Directorate in Oslo (record no. 07/324) and the Regional Committee for Medical and Health Research Ethics, South-East Norway (record no. S.-06353b). For permission to undertake the study in Denmark, we thank the Royal Danish National Archives, Kalvebod Brygge 34, DK-1560 Copenhagen K, comprising the Provincial Archives of Zealand (record no. 2000-441-0023), the Danish Data Protection Office (record no. 2000-41-0184), the Danish Scientific-Ethical Committees (record no. 01-224/01), and the Danish Board of Health (record no.123-63-2000), Faculty of Health and Medical Science, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen N.The Travel Found, Oslo University, is thanked for financial support for a study trip to the Faroe Islands.

Publisher Copyright:
© 2022, The Author(s).

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