chromosomal mutations

• Genome content


  Chromosome number in a nucleus, and relative size and shape of each chromosome are species-specific
• While chromosome number varies widely among species, closely related species tend to have similar numbers
• Each chromosome pair in a diploid genome has a distinct size, shape, and genetic content
• Chromosome territories


  Specific regions that chromosomes are partitioned into during interphase
• Chromosomes do not occupy the same territory in each nucleus, but once confined to a territory, a chromosome does not leave until the M phase is initiated
• Chromosomes are active within their territories and move, twist, and turn during transcription and DNA replication
• Chromosomes appear to be anchored in their territories by their centromeres
• Interchromosomal domains


  Regions between chromosome territories that allow movement of proteins, enzymes, and RNA molecules
• Larger, more gene-rich chromosomes are generally near the center of the nucleus and smaller chromosomes with fewer genes are near the periphery
• Karyotype


  An organized visual display of chromosomes as seen by microscopy; it may be used to identify abnormalities in chromosome number or structure
• Autosomal homologs are numbered 1 through 22, in descending order of size. The sex chromosomes are identified separately.
• Chromosome arms


  Segments of unequal length on a chromosome, divided by the centromere
• Short arm (p arm)

  The shorter of the two chromosome arms
• Long arm (q arm)


  The longer of the two chromosome arms
• Chromosome Shapes


  • Metacentric: Centromere near the middle
  • Submetacentric: Centromere between the center and the tip
  • Acrocentric: Centromere close to one end
  • Telocentric: Centromere at the tip, no p arm
• Fluorescent in situ hybridization (FISH)


  Uses molecular probes to detect a target sequence; sequences may be gene-specific
• Chromosome banding


  Allows cytogeneticists to identify each chromosome in a karyotype based on size, shape, and banding pattern
• G (Giemsa) banding


  The standard for human chromosome banding, with distinct and reproducible patterns
• Euchromatin


  Regions that contain actively expressed genes and are less condensed
• Heterochromatin


  Regions that are tightly condensed and contain many fewer expressed genes
• Nondisjunction


  The failure of chromosomes and sister chromatids to properly separate during cell division
• Euploid


  The number of complete chromosome sets (e.g., n, 2n, 3n)
• Aneuploid


  A number of chromosomes that is not euploid
• Nondisjunction in meiosis I

  Failure of homologs to separate; gametes produced are n+1 or n-1
• Nondisjunction in meiosis II

  Failure of sister chromatids to separate normally; two gametes affected, two normal
• Gene dosage


  The number of copies of a gene; aneuploidy alters dosage of all the genes on the affected chromosome
• Most animals are highly sensitive to changes in gene dosage, while plants tolerate gene dosage changes more readily
• More than half of spontaneously aborted human pregnancies carry abnormalities of chromosome number or structure
• The risk of Down syndrome (trisomy 21) increases with maternal age
• DSCR (Down syndrome critical region)

  A portion of chromosome 21 correlated with the majority of Down syndrome symptoms
• DYRK


  A candidate gene on chromosome 21 that makes a major contribution to Down syndrome
• DSCAM


  A gene on chromosome 21 associated with formation of the heart and nervous system
• SHOX


  A gene on the X chromosome that is not inactivated by dosage compensation; insufficient copies lead to Turner syndrome
• Mosaicism


  Development of cells with different chromosome numbers due to mitotic nondisjunction early in embryogenesis
• Uniparental disomy


  When both copies of a homologous chromosome pair arise from the same parent
• DSCAM


  The gene DSCAM has a homolog in mice and fruit flies that is associated with formation of the heart and nervous system
• Turner Syndrome


  Turner syndrome is a monosomy of the X chromosome, with no second sex chromosome (X O)
• SHOX

  In X O embryos, the single copy of the gene SHOX, which is not inactivated by dosage compensation, is insufficient to direct normal development
• Mosaicism


  Mosaicism can develop as a result of mitotic nondisjunction early in embryogenesis
• Turner syndrome mosaicism


  • 25–30% of Turner syndrome cases occur in females who are mosaic, with some 45, X O cells and some 46, X X
  • Some Turner syndrome individuals carry 47, X X X cells too