Chromosome Mutations:

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Chapter 6

• Chromosome Mutations
• Variation in Number and Arrangement

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Modification at Chromosome Level

• Modifications to the DNA structure is not only at
  the gene level
  
• Deviation from the normal 2n diploid number of
  chromosomes
  
• Modifications can be change in number, deletion
  or duplication of genes or segments of
  chromosomes, rearrangement of the genetic
  material either within or among chromosomes
• chromosome mutation or chromosome aberrations
• pass on to offspring in a predictable manner
  unique genetic outcome

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Terminology

• Aneuploidy organism gains or looses one or more
  chromosomes but not a complete set
  
• Monosomy loose a single chromosome
• Trisomy gain of a single chromosome
• Euploidy complete haploid set of chromosomes
  are present
  
• Polyploidy more that 2 sets are present
• Triploid 3 sets tetraploid - 4 sets etc.

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Variation in Number

• Caused by non-disjunction
• Paired homologs fail to disjoin during
  segregation results in non-disjunction
  
• Occurs during meiosis I or meiosis II
• if in meiosis I then 2 cells with 2 copies of the
  chromosome and 2 cells without that chromosome
  
• if in meiosis II then only 1 cell with 2 copies
  of the chromosome, 1 without that chromosome and
  2 normal cells
  
• results in trisomy or monosomy

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Monosomy 2n-1

• May have severe phenotypic effects
• Usually monosomy of autosomal chromosomes is not
  well tolerated
  
• In Drosophila
• see missing chromosome IV
• slow to develop, reduced body size and impaired
  variability
  
• monosomy of II or III must be lethal as none have
  ever been recovered

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Aneuploidy

• Usually 1 copy of the gene is sufficient but if
  that gene is recessive lethal, then the organism
  may die
  
• Aneuploidy better tolerated in plants
• maize, tobacco, evening primrose and jimson weed
• usually less viable than diploid derivatives
• monosomic pollen grains rarely viable

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Segmental Deletion

• Rarely see autosomal monosomy after birth,
  usually dont survive embryonic/fetal
  development
  
• Survivors with partial monosomy part of the
  chromosome is missing segmental deletion

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Cri-du-chat Syndrome

• Missing part of short arm of chromosome 5 46,5p
  (all chromosomes but a piece of p arm of 5)
  
• Anatomical malformations, gastrointestinal and
  cardiac complications, mental retardation, also
  glottis and larynx is abnormal so the cry like a
  meowing cat
• 1 in 50,000 births, usually a sporadic event
  during gamete formation
  
• larger the deletion of p arm more dramatic
  effect on child
  
• p arm contains the TERT gene which is telomerase
  transcriptase that maintains the telomeres
  during DNA replication

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Trisomy

• Addition of a chromosome to the diploid number
• Usually a parallel monosomy individual is more
  viable especially if it is a small chromosome
  
• Large autosome trisomy is usually lethat in
  animals and Drosophila
  
• Trisomic plants are viable but phenotype may be
  altered
  
• usually grow slower, depends on which chromosome
  is in triplicate

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Down Syndrome

• Only human autosomal trisomy that survive past
  1st birthday 3 copies of chromosome 21
  47,21, 1 in 800 live births
  
• Have very characteristic facial, hand and finger
  features, psychmotor and mental development is
  slow
  
• Prone to respiratory disease and heart
  malformation, increased incidence in leukemia
  
• Usually display a subset of phenotypic
  characteristics

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Down Syndrome Critical Region

• May be a critical region on chromosome 21 that
  is dosage sensitive with in 3 copies, responsible
  for many of the phenotypes seen Down syndrome
  critical region
• Made a mouse with 3 21s but didnt display
  characteristics of syndrome

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Maternal Age and Down Syndrome

• Extra 21 may be from mom or dad but 95 are
  maternal
  
• 1 in 1000 at 30 years old
• 1 in 100 at 40 years old
• 1 in 50 at 45 years old
• 50 of affected births is in women old
  
• Not sure if the age of the ovum is the issue or
  not
  
• Genetic counseling in older women may recommend
  amniocentesis or chorionic villus sampling look
  at karyotype of child

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Inheritance of Down Syndrome

• Not thought to an inheritable disorder but it
  does tend to run in families
  
• Familial Down Syndrome caused by a translocation
  of chromosome 21
  
• different cause of the aberrant chromosomes