Principles for the Buffering of Genetic Variation

Most genetic research has used inbred organisms and has not explored the complexity of natural genetic variation present in outbred populations. The translation of genotype to phenotype is complicated by gene interactions observed as epistasis, canalization, robustness, or buffering. Analysis of double mutations in inbred experimental organisms suggests some principles for gene interaction that may apply to natural variation as well. The buffering of variation in one gene is most often due to a small number of other genes that function in the same biochemical process. However, buffering can also result from genes functioning in processes extrinsic to that of the primary gene.

[1]  C. Waddington.  Canalization of Development and the Inheritance of Acquired Characters , 1942, Nature.

[2]  A. Fraser,et al.  Selection for an Invariant Character—‘Vibrissa Number’—in the House Mouse , 1958, Nature.

[3]  H. Kacser,et al.  The molecular basis of dominance. , 1981, Genetics.

[4]  D. Hartl,et al.  Metabolic flux and fitness. , 1987, Genetics.

[5]  K. Gärtner,et al.  A third component causing random variability beside environment and genotype. A reason for the limited success of a 30 year long effort to standardize laboratory animals? , 1990, Laboratory animals.

[6]  M. Kimura,et al.  Recent development of the neutral theory viewed from the Wrightian tradition of theoretical population genetics. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[7]  D. Tautz,et al.  Redundancies, development and the flow of information. , 1992, BioEssays : news and reviews in molecular, cellular and developmental biology.

[8]  D. Drubin,et al.  Synthetic-lethal interactions identify two novel genes, SLA1 and SLA2, that control membrane cytoskeleton assembly in Saccharomyces cerevisiae , 1993, The Journal of cell biology.

[9]  S. Austad,et al.  Selecting animal models of human aging: inbred strains often exhibit less biological uniformity than F1 hybrids. , 1994, Journal of gerontology.

[10]  J. Zieleński,et al.  Cystic fibrosis: genotypic and phenotypic variations. , 1995, Annual review of genetics.

[11]  G. Blobel,et al.  Two novel related yeast nucleoporins Nup170p and Nup157p: complementation with the vertebrate homologue Nup155p and functional interactions with the yeast nuclear pore-membrane protein Pom152p , 1995, The Journal of cell biology.

[12]  K. Herrup,et al.  Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. , 1995, Science.

[13]  N. Schork,et al.  Who's afraid of epistasis? , 1996, Nature Genetics.

[14]  C. F. Hardy.  Characterization of an essential Orc2p-associated factor that plays a role in DNA replication , 1996, Molecular and cellular biology.

[15]  J. Witte,et al.  Genetic dissection of complex traits. , 1994, Nature genetics.

[16]  M. Steinberg,et al.  Modulation of the phenotypic diversity of sickle cell anemia. , 1996, Hemoglobin.

[17]  Ritsert C. Jansen,et al.  Complex interactions of new quantitative trait loci, Sluc1, Sluc2, Sluc3, and Sluc4, that influence the susceptibility to lung cancer in the mouse , 1996, Nature Genetics.

[18]  A. Hart,et al.  Gene interaction and single gene effects in colon tumour susceptibility in mice , 1996, Nature Genetics.

[19]  L. Cavalli-Sforza,et al.  Genetic variation and human disease , 1996 .

[20]  K. H. Wolfe,et al.  Molecular evidence for an ancient duplication of the entire yeast genome , 1997, Nature.

[21]  A. Wilkins,et al.  Canalization: a molecular genetic perspective. , 1997, BioEssays : news and reviews in molecular, cellular and developmental biology.

[22]  A. Minelli,et al.  Molecules, developmental modules, and phenotypes: a combinatorial approach to homology. , 1998, Molecular phylogenetics and evolution.

[23]  C. Nusbaum,et al.  Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. , 1998, Science.

[24]  S. Lindquist,et al.  Hsp90 as a capacitor for morphological evolution , 1998, Nature.

[25]  P. Sternberg,et al.  Genetics of RAS signaling in C. elegans. , 1998, Trends in genetics : TIG.

[26]  A. Imasheva,et al.  Variation in morphological traits of Drosophila melanogaster (fruit fly) under nutritional stress , 1999, Heredity.

[27]  M. Corey,et al.  Detection of a cystic fibrosis modifier locus for meconium ileus on human chromosome 19q13 , 1999, Nature Genetics.

[28]  U. Alon,et al.  Robustness in bacterial chemotaxis , 2022 .

[29]  L. Kruglyak.  Prospects for whole-genome linkage disequilibrium mapping of common disease genes , 1999, Nature Genetics.

[30]  E. Lander,et al.  Characterization of single-nucleotide polymorphisms in coding regions of human genes , 1999 .

[31]  J. York,et al.  A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export. , 1999, Science.

[32]  E R McCabe,et al.  Phenotypes of patients with "simple" Mendelian disorders are complex traits: thresholds, modifiers, and systems dynamics. , 2000, American journal of human genetics.

[33]  Joseph H. Nadeau,et al.  The roads from phenotypic variation to gene discovery: mutagenesis versus QTLs , 2000, Nature Genetics.

[34]  Michael E. Cusick,et al.  The Yeast Proteome Database (YPD) and Caenorhabditis elegans Proteome Database (WormPD): comprehensive resources for the organization and comparison of model organism protein information , 2000, Nucleic Acids Res..

[35]  G. Fink,et al.  A Saccharomyces gene family involved in invasive growth, cell-cell adhesion, and mating. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[36]  S. Rutherford,et al.  From genotype to phenotype: buffering mechanisms and the storage of genetic information , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[37]  S. Antonarakis,et al.  OMIM passes the 1,000-disease-gene mark , 2000, Nature Genetics.

[38]  A. Wagner.  Robustness against mutations in genetic networks of yeast , 2000, Nature Genetics.

[39]  J. Doyle,et al.  Robust perfect adaptation in bacterial chemotaxis through integral feedback control. , 2000, Proceedings of the National Academy of Sciences of the United States of America.