Effects Of Aneuploidy Research Articles

Mechanistic Plasticity of Sexual Reproduction and Meiosis in the Candida Pathogenic Species Complex

Candida species are microbial pathogens originally thought to be asexual, but several are now recognized as sexual or parasexual. Candida albicans, the most common fungus infecting humans, is an obligate diploid with a parasexual cycle involving mating, recombination, and genome reduction but no recognized meiosis. Others (C. lusitaniae, C. guilliermondii) are haploid, and their mating produces spores, suggestive of complete meiotic sexual cycles. However, comparative genomic analysis reveals that these species lack key meiotic components, including the recombinase Dmc1 and cofactors (Mei5/Sae3), synaptonemal-complex proteins (Zip1-Zip4/Hop1), and the crossover interference pathway (Msh4/5). Here we elucidate the structure and functions of the mating-type (MAT) locus and establish that C. lusitaniae undergoes meiosis during its sexual cycle. The MAT-encoded a2 (high-mobility group) and alpha1 (alpha domain) factors specify a and alpha cell identity, whereas the a1 homeodomain protein drives meiosis and sporulation and functions without its canonical heterodimeric partner, alpha2. Despite the apparent loss of meiotic genes, C. lusitaniae undergoes meiosis during sexual reproduction involving diploid intermediates, frequent SPO11-dependent recombination, and whole-genome reduction generating haploid progeny. The majority of meiotic progeny are euploid, but approximately one-third are diploid/aneuploid. The cell identity and meiotic pathways have been substantially rewired, and meiotic generation of both recombinant and aneuploid progeny may expand genetic diversity. These findings inform our understanding of sexual reproduction in pathogenic microbes and the evolutionary plasticity of the meiotic machinery, with implications for the sexual nature of C. albicans and the generation and consequences of aneuploidy in biology and medicine.

Causes and consequences of aneuploidy.

Causes and consequences of aneuploidy.

New CRIME plots

In the mid‐1990s, the chromosome region maintenance 1 (Crm1) protein was identified in yeast as the product of a gene that is essential for proliferation and chromosome stability (Nishi et al , 1994). Its human homologue, CRM1, was subsequently shown to interact with the nucleoporin CAN, which is a component of oncogenic fusion proteins found in leukaemia cells (Fornerod et al , 1997). These authors also noticed a homologous domain at the amino‐terminus of CRM1, importin β and other proteins—now known to interact with the GTPase Ran—and named it the CRIME domain for ‘CRM1, importin β etc’. Several laboratories soon discovered that CRM1 is the export vector for proteins from the nucleus to the cytoplasm and that it recognizes the nuclear export signal (NES) in these proteins. Export requires RanGTP to stabilize the complexes that are formed by CRM1 and NES‐containing proteins. These data shifted the focus towards the export function of CRM1 and, since then, its involvement in the cell cycle has been somewhat neglected. However, recent findings now put CRM1 at the front of the mitotic stage and contribute to a more general reappraisal of the role of transport factors in mitosis. In the August issue of Nature Cell Biology , Wang et al (2005) have addressed the role of CRM1 in the control of centrosome duplication. Centrosomes are major microtubule (MT)‐organizing centres in mammalian somatic cells and form the spindle poles at mitosis. More than a century ago, Boveri observed that tumour cells typically contain many centrosomes compared with only one or two in normal cells. Whether supernumerary centrosomes are a cause or a consequence of aneuploidy is still a matter of debate, but it has been suggested that their presence can facilitate the propagation of aneuploidy, particularly in certain cancer types (D'Assoro et al , 2002). A complex regulatory …

Alteration of Gene Expression by Chromosome Loss in the Postnatal Mouse Brain

Frequent chromosomal aneuploidy has recently been discovered in normal neurons of the developing and mature murine CNS. Toward a more detailed understanding of aneuploidy and its effects on normal CNS cells, we examined the genomes of cells in the postnatal subventricular zone (SVZ), an area that harbors a large number of neural stem and progenitor cells (NPCs), which give rise to neurons and glia. Here we show that NPCs, neurons, and glia from the SVZ are frequently aneuploid. Karyotyping revealed that approximately 33% of mitotic SVZ cells lost or gained chromosomes in vivo, whereas interphase fluorescence in situ hybridization demonstrated aneuploidy in postnatal-born cells in the olfactory bulb (OB) in vivo, along with neurons, glia, and NPCs in vitro. One possible consequence of aneuploidy is altered gene expression through loss of heterozygosity (LOH). This was examined in a model of LOH: loss of transgene expression in mice hemizygous for a ubiquitously expressed enhanced green fluorescent protein (eGFP) transgene on chromosome 15. Concurrent examination of eGFP expression, transgene abundance, and chromosome 15 copy number demonstrated that a preponderance of living SVZ and OB cells not expressing eGFP lost one copy of chromosome 15; the eGFP transgene was lost in these cells as well. Although gene expression profiling revealed changes in expression levels of several genes relative to GFP-expressing controls, cells with LOH at chromosome 15 were morphologically normal and proliferated or underwent apoptosis at rates similar to those of euploid cells in vitro. These findings support the view that NPCs and postnatal-born neurons and glia can be aneuploid in vivo and functional gene expression can be permanently altered in living neural cells by chromosomal aneuploidy.

Genetic variation in dosage effects in maize aneuploids

In maize (Zea mays L.), the consequences of aneuploidy have been well documented, however, genetic variation in the responses to aneuploidy has not been examined. Using simple B-A translocation stocks to generate a dosage series involving segments from 14 chromosome arms, we tested for the presence of genetic variation for dosage responses in maize by examining reciprocal and maternal genotype effects on the dosage responses. Reciprocal effects examined whether there were differences between two distinctly different inbred backgrounds, Mo17Ht and B73Ht, in how they responded to loss or gain of a B73Ht segment in the Mo17Ht x B73Ht (TB) F1 cross versus a Mo17Ht segment in the B73Ht x Mo17Ht (TB) F1 cross. Maternal genotype effects questioned whether different inbred backgrounds, Sc41R, T8, and either Mo17Ht or B73Ht (depending on the male), when used as females responded differently to the loss or gain of a chromosome arm segment from the same male (either B73Ht TB or Mo17Ht TB) in an F1 cross. Numerous examples of reciprocal and maternal genetic effects were identified in this study. Most of the genetic effects were due to differences in magnitude of response rather than direction; however, tassel-branch number involving the 5S chromosome segment in the B73Ht male background and the 7L chromosome segment in the Mo17Ht male background showed a trend toward the maternal genotype effects being due to differences in the direction of the response. Key words : quantitative traits, corn, B-A translocations, dosage analysis.

FINGER-PRINT PATTERN AND THE SEX CHROMOSOMES

Evidence suggests that the finger-tip pattern size, as measured by the total ridge-count, is an autosomal trait which is independently influenced by the sex-chromosome complement, normal or abnormal. In males, the presence of each X-chromosome diminishes the total number of ridges in the patterns nearly three times as much as does the presence of each Y-chromosome. In females, the reduction of ridges, as the X-chromosome complement increases, is less regular. These phenomena are discussed in relation to embryonic oedema or dehydration as possible consequences of aneuploidy.