Inversions

1
Chapter 6

• Part 3

2
Inversions

• May have little impact on individuals
  interesting to geneticists
• Heterozygotes for inversions may produce aberrant
  gametes that will have an impact on offspring
• Chromosomes may not be able to synapse which
  means the number of chromosomes in the new cells
  will be off

3
Gamete Formation

• No crossing-over, get 2 normal and 2 inverted
  gametes
• If a single cross-over occurs in the loop of a
  paracentric inversion get 2 parent chromatids
  and 2 recombinant chromatids
• 1 recombinant is dicentric (2 centromeres) and
  may be pulled in 2 directions
• usually breaks and get part in each daughter cell
• 1 recombinant is acentric (0 centromeres) and
  will move randomly or be lost
• gametes will be deficient in genetic material
• fertilization may result in lethality

4
Gamete Formation

• Similar happenings in pericentric inversion
• See duplication and deletions
• Plants may have lethality prior to fertilization,
  inviable seeds
• Animals may have fertilization because gametes
  formed before meiotic error
• Both lead to decreased viability
• Inversion suppresses the recovery of cross-over
  products when exchange occurs in inverted region

5
Translocations

• Movement of a segment to a new location in the
  genome
• Reciprocal translocation between 2
  non-homologous chromosomes 2 breaks in simple
  translocation
• Requires 4 breaks in you move an interior
  segment
• Consequence similar to inversions no loss or
  gain of DNA doesnt necessarily decrease viability

6
Unusual Synapse

• During meiosis the synapse may be strange
  dependent on the translocation
• Usually create unbalanced gametes, not
  necessarily to crossing-over
• Follow homologous centromeres to see unbalanced
  gametes

7
2 Outcomes

• 1 chromosome moves to a pole and takes either 3
  or 4 with, 2 moves to the other pole and takes
  the other with it
• Plan 1 1,4 are normal and 2,3 are translocated
  but complete balanced, alternate segregation
• Plan 2 1,3 have 2 Ds and no K and 2,4 have 2 Ks
  but no Ds unbalanced, adjacent segregation

8
Plan 2

• Leads to lethality if fertilized
• 50 of progeny survive from heterozygous parent
  for translocation semisterility
• Part of reproductive fitness and evolution
• Unbalanced is partial monosomy/trisomy depending
  on the gamete that is fertilized
• leads to birth defects

9
Human Translocations

• Breaks the extreme ends of short arm of
  acrocentric chromosomes (non-homologous) and fuse
  the remaining large arm together
• short arm is lost
• creates a large submetacentric or metacentric
  chromosome Robertsonian translocation

10
Familial Down Syndrome

• 14/21, D/G translocation
• Parent is phenotypically normal even though only
  45 chromosomes
• Offspring
• ¼ normal 21 and 14
• ¼ Down syndrome, 47,21 (2 normal and 1 in
  translocation)
• ¼ normal but carrier of translocation
• ¼ monosomic lethal
• End missing from 21 and 14 code for rRNA genes
  and since redundant can live without

11
Fragile Sites in Humans

• Areas that look like a gap may be susceptible
  to breakage
• Cause of fragility is unknown may be that the
  chromatin is not tightly packed, originally only
  saw in tissue culture but linked to observed
  abnormal phenotypes
• mental retardation and cancer

12
Fragile X Syndrome (Martin-Bell Syndrome)

• Folate sensitive site on the X chromosome
  inherited mental retardation
• 1 in 4000 boys, 1 in 8000 girls because the
  fragile X is dominant
• 80 boys are retarded and only 30 for girls
• Long narrow face, protruding chins, enlarged ears
  and increased testicular size

13
Possible Cause

• Gene near the fragile site is FMR-1 a sequence
  of 3 nucleotides that are repeated many times,
  trinucleotide repeat, also seen in Huntingtons
  disease
• More repeats correspond to Fragile X
• 6-54 normal, pass on normal number to offspring
• 55 230 carriers, do not develop syndrome but
  transmit to offspring, their number of repeats
  can increase over subsequent generations
  genetic anticipation
• reach 230 repeats then the next generation gets
  more severe
• happens only when mom gives the Fragile X and not
  dad
• male offspring more likely receive the increased
  repeat than females
• gt230 express syndrome
• FMR-1 is inactivated by methylation, RNA binding
  protein in the brain that move mRNA from nucleus
  to cytoplasm, (mRNA have increased G content)