Inclusion Of Chromosomes Research Articles

How to Include Chromosome X in Your Genome‐Wide Association Study

In current genome-wide association studies (GWAS), the analysis is usually focused on autosomal variants only, and the sex chromosomes are often neglected. Recently, a number of technical hurdles have been described that add to a reluctance of including chromosome X in a GWAS, including complications in genotype calling, imputation, and selection of test statistics. To overcome this, we provide a "how to" guide for analyzing X chromosomal data within a standard GWAS. Following a general pipeline for GWAS, we highlight the steps in which the X chromosome requires specific attention, and we give tentative advice for each of these. Through this, we show that by selection of sensible algorithms and parameter settings, the inclusion of chromosome X in GWAS is manageable. Closing this gap is expected to further elucidate the genetic background of complex diseases, especially of those with sex-specific features.

Increased efficiency of preimplantation genetic diagnosis for aneuploidy by testing 12 chromosomes

One of the most important factors in increasing the screening potential of preimplantation genetic diagnosis (PGD) for aneuploidy is to increase the number of chromosomes analysed. Inclusion of chromosomes 8, 14 and 20 to the standard set of chromosomes X, Y, 13, 15, 16, 17, 18, 21 and 22 allows the analysis of 12 chromosomes in three rounds of fluorescent in-situ hybridization (FISH) without decreasing the efficiency of the technique. Pregnancy rate was significantly increased when only embryos that had been diagnosed as normal for the 12 chromosomes analysed were transferred compared with transfer of embryos with any abnormality for chromosomes 8, 14 or 20 (P < 0.05). This study proves that the high efficiency and practical feasibility of FISH analysis of 12 chromosomes in PGD for aneuploidy is a superior approach than the standard nine-chromosome analysis in order to screen for abnormalities.

The Origin of the Eukaryotic Cell Based on Conservation of Existing Interfaces

Current theories about the origin of the eukaryotic cell all assume that during evolution a prokaryotic cell acquired a nucleus. Here, it is shown that a scenario in which the nucleus acquired a plasma membrane is inherently less complex because existing interfaces remain intact during evolution. Using this scenario, the evolution to the first eukaryotic cell can be modeled in three steps, based on the self-assembly of cellular membranes by lipid-protein interactions. First, the inclusion of chromosomes in a nuclear membrane is mediated by interactions between laminar proteins and lipid vesicles. Second, the formation of a primitive endoplasmic reticulum, or exomembrane, is induced by the expression of intrinsic membrane proteins. Third, a plasma membrane is formed by fusion of exomembrane vesicles on the cytoskeletal protein scaffold. All three self-assembly processes occur both in vivo and in vitro. This new model provides a gradual Darwinistic evolutionary model of the origins of the eukaryotic cell and suggests an inherent ability of an ancestral, primitive genome to induce its own inclusion in a membrane.

Spontaneous and spindle poison-induced micronuclei and chromosome non-disjunction in cytokinesis-blocked lymphocytes from two age groups of women

Fluorescence in situ hybridization (FISH) was used to evaluate spontaneous and aneuploidogen-induced micronucleus frequencies and non-disjunction of chromosomes X and 8 in cultured binucleated lymphocytes of women of two age groups. Demecolcine and vincristine were used as model aneuploidogens to induce micronuclei and chromosome malsegregation. Four of the women were aged 22-26 (mean 24.3) years and four 47-50 (mean 49.0) years. Pancentromeric FISH was applied to micronuclei to identify chromosomes and double-color centromeric FISH, performed in binucleates of two young and two older women, was used to assess the involvement of chromosomes X and 8 in micronuclei and non-disjunction. It was confirmed that age increases micronucleus frequency. Micronuclei containing whole chromosomes predominated in older females. Age also enhanced micronuclei containing acentric chromosome fragments. The inclusion of chromosomes X and 8 in micronuclei was enhanced by age and chromosome X was generally overrepresented. Non-disjunction of chromosomes X and 8 also increased with age, chromosome X being the more sensitive. Treatment of lymphocytes with vincristine and demecolcine increased micronucleus frequency and malsegregation of chromosomes X and 8 in both age groups. Comparison of the estimated frequencies of micronucleation and non-disjunction for all human chromosomes showed that non-disjunction is the main type of chromosome malsegregation.