Lethal mutations with fluctuating heterozygous effect: the lethal force of effective dominance.

Journal of Human Genetics
Andrew D J Overall, David Waxman

Abstract

The theory of population genetics leads to the expectation that in very large populations the frequencies of recessive lethal mutations are close to the square root of the mutation rate, corresponding to mutation-selection balance. There are numerous examples where the frequencies of such alleles are orders of magnitude larger than this result. In this work we theoretically investigate the role of temporal fluctuations in the heterozygous effect (h) for lethal mutations in very large populations. For fluctuations of h, around a mean value of [Formula: see text], we find a biased outcome that is described by an effective dominance coefficient, heff, that is generally less than the mean dominance coefficient, i.e., [Formula: see text]. In the case where the mean dominance coefficient is zero, the effective dominance coefficient is negative: heff < 0, corresponding to the lethal allele behaving as though overdominant and having an elevated mean frequency. This case plausibly explains mean allele frequencies that are an order of magnitude larger than the equilibrium frequency of a recessive allele with a constant dominance coefficient. Our analysis may be relevant to explaining lethal disorders with anomalously high frequencies, su...Continue Reading

References

Nov 1, 1991·Medical Hypotheses·D M Rodman, S Zamudio
Feb 25, 1988·Nature·B Spyropoulos
Dec 7, 1995·Nature·B GentonD Mokela
May 29, 2000·QJM : Monthly Journal of the Association of Physicians·K P Dawson, P M Frossard
May 7, 2002·Evolution; International Journal of Organic Evolution·Philip W Hedrick
Oct 4, 2006·Journal of the Royal Society, Interface·Eric M Poolman, Alison P Galvani
Apr 30, 2008·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Philip M Farrell
Dec 17, 2009·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Graham Bell
Sep 15, 2012·Trends in Ecology & Evolution·Philip W Hedrick
Jan 11, 2014·PloS One·Toni I GossmannAdam Eyre-Walker
Dec 20, 2014·The Journal of Heredity·Philip W Hedrick
Apr 19, 2016·Emerging Infectious Diseases·Laura Arzuza-OrtegaAlfonso J Rodríguez-Morales
Sep 29, 2017·PLoS Genetics·Carlos Eduardo G AmorimMolly Przeworski
Apr 21, 2018·Thorax·Philippe GlaziouMario Raviglione
Apr 18, 2020·Frontiers in Genetics·David Waxman, Andrew D J Overall

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik
C C MillerL D McGilliard
BioRxiv : the Preprint Server for Biology
Carlos Eduardo Guerra AmorimM. Przeworski
© 2021 Meta ULC. All rights reserved