Maternal-zygotic epistasis and the evolution of genetic diseases.
Many birth defects and genetic diseases are expressed in individuals that do not carry the disease causing alleles. Genetic diseases observed in offspring can be caused by gene expression in mothers and by interactions between gene expression in mothers and offspring. It is not clear whether the underlying pattern of gene expression (maternal versus offspring) affects the incidence of genetic disease. Here we develop a 2-locus population genetic model with epistatic interactions between a maternal gene and a zygotic gene to address this question. We show that maternal effect genes that affect disease susceptibility in offspring persist longer and at higher frequencies in a population than offspring genes with the same effects. We find that specific forms of maternal-zygotic epistasis can maintain disease causing alleles at high frequencies over a range of plausible values. Our findings suggest that the strength and form of epistasis and the underlying pattern of gene expression may greatly influence the prevalence of human genetic diseases.
Priest
Nicholas K
NK
Department of Biology & Biochemistry, University of Bath, Bath BA27AY, UK.
Wade
Michael J
MJ
D000818:Animals; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D030342:Genetic Diseases, Inborn; D020022:Genetic Predisposition to Disease; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D015053:Zygote
Hum Genet. 2006 Jan;118(5):652-64
16283388
Epidemiology. 2005 May;16(3):288-93
15824542
Lancet. 1973 Jun 9;1(7815):1267-71
4126070
Biol Reprod. 1991 Jan;44(1):62-8
2015352
J Bone Miner Res. 2005 Mar;20(3):365-76
15746981
Nat Rev Genet. 2007 Mar;8(3):185-95
17279094
Nat Genet. 1995 Nov;11(3):241-7
7581446
Am J Hum Genet. 2000 Sep;67(3):623-30
10930360
PLoS One. 2008 Sep 04;3(9):e3131
18769549
Hum Mol Genet. 2009 Oct 15;18(R2):R202-10
19808797
Ann Hum Genet. 1955 Jun;19(4):262-8
14388532
Heredity (Edinb). 2002 Oct;89(4):300-10
12242647
Genetics. 1931 Mar;16(2):97-159
17246615
Genetics. 1967 Sep;57(1):79-94
6077532
Genet Epidemiol. 2003 Jan;24(1):1-13
12508251
Genetics. 1954 Nov;39(6):859-82
17247525
Ann Hum Genet. 2004 Nov;68(Pt 6):646-57
15598223
Trends Genet. 2001 Sep;17(9):502-10
11525833
Genetica. 2001;112-113:59-69
11838787
Science. 1994 Sep 30;265(5181):2037-48
8091226
Trends Genet. 2004 Dec;20(12):640-7
15522460
J Med Genet. 2004 Apr;41(4):256-60
15060097
Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10925-9
1438298
Am J Epidemiol. 1998 Nov 1;148(9):893-901
9801020
Genetics. 1995 May;140(1):403-9
7635303
Trends Ecol Evol. 1998 Feb 1;13(2):64-9
21238202
Am J Hum Genet. 1982 Nov;34(6):866-73
7180845
Q Rev Biol. 2005 Sep;80(3):317-36
16250466
Am J Med Genet B Neuropsychiatr Genet. 2006 Jan 5;141B(1):1-6
16342283
Genetics. 1998 Jul;149(3):1167-71
9649511
Nucleic Acids Res. 2005 Jan 1;33(Database issue):D514-7
15608251
Genetics. 1989 May;122(1):193-203
2731729
Genet Epidemiol. 2007 Dec;31(8):813-33
17549757
Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3315-20
12601179
Evolution. 2000 Dec;54(6):1882-98
11209768
Biol Reprod. 2004 Jun;70(6):1701-9
14960490
Immunogenetics. 2005 Sep;57(8):549-58
16086172
Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4655-60
12640144
PLoS Genet. 2005 Nov;1(5):e57
16299585
Hum Reprod Update. 2002 Jul-Aug;8(4):323-31
12206467
Genetica. 2007 Jan;129(1):37-43
16955333
Ann Hum Biol. 2004 Mar-Apr;31(2):139-58
15204358