The Slavic NBN Founder Mutation: A Role for Reproductive Fitness?

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F16%3A10332863" target="_blank" >RIV/00064203:_____/16:10332863 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/16:10332863

Result on the web

<a href="http://dx.doi.org/10.1371/journal.pone.0167984" target="_blank" >http://dx.doi.org/10.1371/journal.pone.0167984</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0167984" target="_blank" >10.1371/journal.pone.0167984</a>

Result language

angličtina

Original language name

The Slavic NBN Founder Mutation: A Role for Reproductive Fitness?

Original language description

The vast majority of patients with Nijmegen Breakage Syndrome (NBS) are of Slavic origin and carry a deleterious deletion (c.657de15; rs587776650) in the NBN gene on chromosome 8q21. This mutation is essentially confined to Slavic populations and may thus be considered a Slavic founder mutation. Notably, not a single parenthood of a homozygous c.657de15 carrier has been reported to date, while heterozygous carriers do reproduce but have an increased cancer risk. These observations seem to conflict with the considerable carrier frequency of c.657de15 of 0.5% to 1% as observed in different Slavic populations because deleterious mutations would be eliminated quite rapidly by purifying selection. Therefore, we propose that heterozygous c.657de15 carriers have increased reproductive success, i.e., that the mutation confers heterozygote advantage. In fact, in our cohort study of the reproductive history of 24 NBS pedigrees from the Czech Republic, we observed that female carriers gave birth to more children on average than female non-carriers, while no such reproductive differences were observed for males. We also estimate that c.657de15 likely occurred less than 300 generations ago, thus supporting the view that the original mutation predated the historic split and subsequent spread of the 'Slavic people'. We surmise that the higher fertility of female c.657de15 carriers reflects a lower miscarriage rate in these women, thereby reflecting the role of the NBN gene product, nibrin, in the repair of DNA double strand breaks and their processing in immune gene rearrangements, telomere maintenance, and meiotic recombination, akin to the previously described role of the DNA repair genes BRCA1 and BRCA2.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

<a href="/en/project/NV15-31899A" target="_blank" >NV15-31899A: Hereditary recessive diseases in Czech Roma – improved diagnostics and search for new causes by the use of homozygosity mapping and exome sequencing.</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

PLoS ONE

ISSN

1932-6203

e-ISSN

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Volume of the periodical

11

Issue of the periodical within the volume

12

Country of publishing house

US - UNITED STATES

Number of pages

18

Pages from-to

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UT code for WoS article

000389587100245

EID of the result in the Scopus database

2-s2.0-85005943170