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Sex chromosome aneuploidy and aging
1Southwest Biomedical Research Institute and Genetrix, Scottsdale, AZ 85260, USA.
Mutation Research
|October 1, 1995
Summary
Sex chromosome loss, including X in females and Y in males, is linked to aging. Measuring this aneuploidy may serve as a novel biomarker for cellular senescence.
Area of Science:
- Genetics
- Cell Biology
- Gerontology
Background:
- Sex chromosome loss, specifically X in females and Y in males, is observed as a natural phenomenon during aging.
- X chromosome loss primarily affects peripheral lymphocytes stimulated by phytohemagglutinin (PHA), while Y chromosome loss is most prominent in bone marrow cells.
- The precise mechanisms underlying Y chromosome loss remain unclear, and pathological consequences of either sex chromosome loss are not definitively established.
Purpose of the Study:
- To investigate the association between sex chromosome loss and the aging process.
- To explore the potential of measuring sex chromosome aneuploidy as a biomarker for cellular senescence.
Main Methods:
- Analysis of X chromosome loss in PHA-stimulated peripheral lymphocytes in females.
- Assessment of Y chromosome loss in bone marrow cells and PHA-stimulated peripheral lymphocytes in males.
- Utilizing Fluorescence In Situ Hybridization (FISH) technology to measure sex chromosome aneuploidy.
Main Results:
- X chromosome loss is linked to premature centromere division, resulting in anaphase lag and micronuclei formation.
- While Y chromosome loss is most apparent in bone marrow, it also occurs in peripheral lymphocytes.
- No significant pathological outcomes have been conclusively linked to X or Y chromosome loss.
Conclusions:
- Sex chromosome loss is a validated phenomenon associated with aging in both sexes.
- Fluorescence In Situ Hybridization (FISH) offers a promising method for quantifying sex chromosome aneuploidy.
- Measuring sex chromosome aneuploidy could serve as a practical assay for assessing cellular senescence and aging.
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Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
Nondisjunction
During meiosis, chromosomes occasionally separate improperly. This occurs due to failure of homologous chromosome separation during meiosis I or failed sister chromatid separation during meiosis II. In some species, notably plants, nondisjunction can result in an organism with an entire additional set of chromosomes, which is called polyploidy. In humans, nondisjunction can occur during male or female gametogenesis and the resulting gametes possess one too many or one too few chromosomes.
X and Y Chromosomes
Among mammals, the gender of an organism is determined by the sex chromosomes. Humans have two sex chromosomes, X and Y. Every human diploid cell has 22 pairs of autosomes and one pair of sex chromosomes. A human female has two X chromosomes, while a male has one X chromosome and one Y chromosome.
The germline cells such as egg and sperm cells carry only half the number of chromosomes, i.e., 22 autosomes and one sex chromosome. All eggs have an X chromosome, while sperm cells can carry an X or...
The germline cells such as egg and sperm cells carry only half the number of chromosomes, i.e., 22 autosomes and one sex chromosome. All eggs have an X chromosome, while sperm cells can carry an X or...
The Y Chromosome Determines Maleness
The Y chromosome is a sex chromosome found in several vertebrates and mammals, including humans. In addition to 22 pairs of autosomes, the human males have one X chromosome and one Y chromosome. In these organisms, the presence or absence of the Y chromosome determines the development of male traits.
Evolution
Around 300 million years ago, the two sex chromosomes diverged from two identical autosomal chromosomes. Over time, the Y chromosome has lost most of its genes, shrinking in size. Today,...
Evolution
Around 300 million years ago, the two sex chromosomes diverged from two identical autosomal chromosomes. Over time, the Y chromosome has lost most of its genes, shrinking in size. Today,...
Meiosis vs. Mitosis
Cell division is necessary for growth and reproduction in organisms. Mitosis aids cell growth and development by dividing somatic cells. In contrast, meiosis causes the division of germ cells and plays an essential role in sexual reproduction. Due to their unique functional requirements, mitosis and meiosis differ from each other in multiple aspects.
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
Nondisjunction
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold sister...

