Reflections on studies of gene expression in aneuploids.

Aneuploidy involves changes in chromosomal copy number compared with normal euploid genotypes. Studies of gene expression in aneuploids in a variety of species have claimed many different types of responses. Studies of individual genes suggest that there are both structural gene dosage effects and compensation in aneuploids, and that subtle trans-acting effects across the genome are quite prevalent. A discussion is presented concerning the normalization procedures for studying gene expression in aneuploids. A careful documentation of the modulations of gene expression in aneuploids should provide insight into the nature of cancerous cells and the basis of aneuploid syndromes.

[1]  D. Tautz,et al.  Autonomous concentration-dependent activation and repression of Krüppel by hunchback in the Drosophila embryo. , 1994, Development.

[2]  J M Delabar,et al.  Classification of human chromosome 21 gene-expression variations in Down syndrome: impact on disease phenotypes. , 2007, American journal of human genetics.

[3]  Maitreya J. Dunham,et al.  Effects of Aneuploidy on Cellular Physiology and Cell Division in Haploid Yeast , 2007, Science.

[4]  J. Birchler,et al.  A trans-acting regulatory gene that inversely affects the expression of the white, brown and scarlet loci in Drosophila. , 1991, Genetics.

[5]  B. S. Baker,et al.  Segmental aneuploidy and the genetic gross structure of the Drosophila genome. , 1972, Genetics.

[6]  J. Birchler.  A study of enzyme activities in a dosage series of the long arm of chromosome one in maize. , 1979, Genetics.

[7]  A. T. Carpenter.  The Joys of Truly Joint Research, With the Great Translocation Hunt As an Example , 2009, Genetics.

[8]  R. Devlin,et al.  The influence of whole-arm trisomy on gene expression in Drosophila. , 1988, Genetics.

[9]  R. Veitia,et al.  The Gene Balance Hypothesis: From Classical Genetics to Modern Genomics , 2007, The Plant Cell Online.

[10]  J. Birchler,et al.  Commonalities in compensation. , 2006, BioEssays : news and reviews in molecular, cellular and developmental biology.

[11]  M. M. Mc Gee,et al.  Understanding the role of aneuploidy in tumorigenesis. , 2009, Biochemical Society transactions.

[12]  R. Veitia,et al.  Gene Dosage Balance in Cellular Pathways , 2004, Genetics.

[13]  R. Veitia,et al.  Exploring the etiology of haploinsufficiency. , 2002, BioEssays : news and reviews in molecular, cellular and developmental biology.

[14]  N. Springer,et al.  Profiling expression changes caused by a segmental aneuploid in maize , 2008, BMC Genomics.

[15]  S. Antonarakis,et al.  Gene expression from the aneuploid chromosome in a trisomy mouse model of down syndrome. , 2004, Genome research.

[16]  Neil J Ganem,et al.  Tetraploidy, aneuploidy and cancer. , 2007, Current opinion in genetics & development.

[17]  Pumin Zhang,et al.  Aneuploidy and tumorigenesis. , 2011, Seminars in cell & developmental biology.

[18]  J. Birchler,et al.  Trans-Acting Dosage Effects on the Expression of Model Gene Systems in Maize Aneuploids , 1994, Science.

[19]  Nicole C Riddle,et al.  Dosage balance in gene regulation: biological implications. , 2005, Trends in genetics : TIG.

[20]  J. Birchler,et al.  Dosage-dependent gene regulation in multicellular eukaryotes: implications for dosage compensation, aneuploid syndromes, and quantitative traits. , 2001, Developmental biology.

[21]  J. Birchler,et al.  Modulation of protein levels in chromosomal dosage series of maize: the biochemical basis of aneuploid syndromes. , 1981, Genetics.

[22]  K. Struhl,et al.  The gradient morphogen bicoid is a concentration-dependent transcriptional activator , 1989, Cell.

[23]  R. Hodgetts.  The response of dopa decarboxylase activity to variations in gene dosage in Drosophila: a possible location of the structural gene. , 1975, Genetics.

[24]  M. Delorenzi,et al.  Natural gene-expression variation in Down syndrome modulates the outcome of gene-dosage imbalance. , 2007, American journal of human genetics.

[25]  Guillaume Blanc,et al.  Functional Divergence of Duplicated Genes Formed by Polyploidy during Arabidopsis Evolution , 2004, The Plant Cell Online.

[26]  C. Pál,et al.  Dosage sensitivity and the evolution of gene families in yeast , 2003, Nature.

[27]  A. Schinzel,et al.  Catalogue of Unbalanced Chromosome Aberrations in Man , 1985 .

[28]  J. Birchler,et al.  Biological consequences of dosage dependent gene regulatory systems. , 2007, Biochimica et biophysica acta.

[29]  G. Moore,et al.  Biochemical and genetic characterization of kynurenine formamidase from Drosophila melanogaster , 1978, Biochemical Genetics.

[30]  Geert J. P. L. Kops,et al.  On the road to cancer: aneuploidy and the mitotic checkpoint , 2005, Nature Reviews Cancer.

[31]  Malin J. Svensson,et al.  Buffering of Segmental and Chromosomal Aneuploidies in Drosophila melanogaster , 2009, PLoS genetics.

[32]  J. Seidman,et al.  Transcription factor haploinsufficiency: when half a loaf is not enough. , 2002, The Journal of clinical investigation.

[33]  J. Winkles,et al.  Drosophila ribosomal RNA stability increases during slow growth conditions. , 1985, The Journal of biological chemistry.

[34]  J. Birchler.  The genetic basis of dosage compensation of alcohol dehydrogenase-1 in maize. , 1981, Genetics.

[35]  S. O’Brien,et al.  Segmental aneuploidy as a probe for structural genes in Drosophila: mitochondrial membrane enzymes. , 1973, Genetics.

[36]  David P. Kreil,et al.  Effects of Aneuploidy on Genome Structure, Expression, and Interphase Organization in Arabidopsis thaliana , 2008, PLoS genetics.

[37]  A. Blakeslee.  NEW JIMSON WEEDS FROM OLD CHROMOSOMES , 1934 .

[38]  J. Lucchesi,et al.  Regulation of enzyme activities in Drosophila. I. The detection of regulatory loci by gene dosage responses. , 1974, Genetical research.

[39]  S. South,et al.  Transcript level alterations reflect gene dosage effects across multiple tissues in a mouse model of down syndrome. , 2004, Genome research.

[40]  D. Hartl,et al.  A portrait of copy-number polymorphism in Drosophila melanogaster , 2007, Proceedings of the National Academy of Sciences.

[41]  J. Birchler,et al.  Dosage dependent modifiers of white alleles in Drosophila melanogaster. , 1993, Genetical research.

[42]  J. C. Hiebert,et al.  Analysis of autosomal dosage compensation involving the alcohol dehydrogenase locus in Drosophila melanogaster. , 1990, Genetics.

[43]  D. Cleveland,et al.  Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis , 2009, Nature Reviews Molecular Cell Biology.

[44]  A. Dufke,et al.  Specific transcriptional changes in human fetuses with autosomal trisomies , 2008, Cytogenetic and Genome Research.

[45]  R. E. Huber,et al.  Genetic and biochemical aspects of trehalase from Drosophila melanogaster , 2004, Biochemical Genetics.

[46]  T. Bremner,et al.  Location and regulation of Drosophila fumarase , 1977 .

[47]  Brian C. Thomas,et al.  Gene-balanced duplications, like tetraploidy, provide predictable drive to increase morphological complexity. , 2006, Genome research.

[48]  R. MacIntyre,et al.  A genetic and developmental analysis of an acid deoxyribonuclease in Drosophila melanogaster , 1978, Biochemical Genetics.

[49]  A. Blakeslee,et al.  CHROMOSOMAL DUPLICATION AND MENDELIAN PHENOMENA IN DATURA MUTANTS. , 1920 .

[50]  S. Bottani,et al.  Cellular reactions to gene dosage imbalance: genomic, transcriptomic and proteomic effects. , 2008, Trends in genetics : TIG.

[51]  H. Jäckle,et al.  Concentration-dependent transcriptional activation or repression by Krüppel from a single binding site , 1991, Nature.

[52]  Michael Freeling,et al.  Many or most genes in Arabidopsis transposed after the origin of the order Brassicales. , 2008, Genome research.

[53]  Ariel Fernández,et al.  Protein Under-Wrapping Causes Dosage Sensitivity and Decreases Gene Duplicability , 2007, PLoS genetics.

[54]  Eugene V Koonin,et al.  A common framework for understanding the origin of genetic dominance and evolutionary fates of gene duplications. , 2004, Trends in genetics : TIG.

[55]  Angelika Amon,et al.  Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells , 2008, Science.

[56]  J. Procunier,et al.  A genetic locus having trans and contiguous cis functions that control the disproportionate replication of ribosomal RNA genes in Drosophila melanogaster. , 1978, Genetics.

[57]  P. S. Carlson.  Locating genetic loci with aneuploids , 2004, Molecular and General Genetics MGG.

[58]  R. Devlin,et al.  Autosomal dosage compensation Drosophila melanogaster strains trisomic for the left arm of chromosome 2. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[59]  J. Williamson,et al.  Genetic and biochemical aspects of sucrase from Drosophila melanogaster , 1978, Biochemical Genetics.

[60]  A. Blakeslee,et al.  1920, Chromosomal duplication and mendelian phenomena in Datura mutants , 1924, Zeitschrift für Induktive Abstammungs- und Vererbungslehre.

[61]  R. Mcdaniel,et al.  GENETICS OF A PRIMARY TRISOMIC SERIES IN BARLEY: IDENTIFICATION BY PROTEIN ELECTROPHORESIS , 1970 .

[62]  M. Levine,et al.  Dose-dependent regulation of pair-rule stripes by gap proteins and the initiation of segment polarity. , 1990, Development.

[63]  S. Izraeli,et al.  Constitutional aneuploidy and cancer predisposition. , 2009, Human molecular genetics.

[64]  R. Guigó,et al.  Global trends of whole-genome duplications revealed by the ciliate Paramecium tetraurelia , 2006, Nature.

[65]  J. Birchler,et al.  Dosage effects on gene expression in a maize ploidy series. , 1996, Genetics.

[66]  H. H. Smith,et al.  EFFECTS OF GENE DOSAGE ON PEROXIDASE ISOZYMES IN DATURA STRAMONIUM TRISOMICS , 1975 .

[67]  J. C. Hall,et al.  Genetics of acetylcholinesterase in Drosophila melanogaster. , 1976, Genetics.