LECTURE 22 LARGE-SCALE CHROMOSOME CHANGES II

1
LECTURE 22 LARGE-SCALE CHROMOSOME CHANGES II

• chapter 15
• overview
• chromosome number
• chromosome structure
• problems

2
CHANGES IN CHROMOSOME NUMBER

• what are the genotypic phenotypic probabilities
  in the progeny of a P cross A/A/A/a ? A/A/A/a?
• P gametes P(A/A) P(A/a) ½, P(a/a) 0
• F1 genotypes P(A/A/A/A) (½)2 ¼
• P(A/A/A/a) 2(½)2 ½
• P(A/A/a/a) (½)2 ¼
• F1 phenotypes all A
• A/A/a/a?
• A/a/a/a?

• autopolyploids

work out these ones for next class
3
OVERVIEW

• 3 classes of chromosome change

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4
OVERVIEW

• 2 general questions to consider...
• is the genome complete?
• is the genome balanced?

5
CHANGES IN CHROMOSOME STRUCTURE

• implications
• chromosome structure mutations ? phenotypes
• abnormal gene ? segmental aneuploids
• abnormal gene
  environment ?
  position effect
• break points ?
  disrupt gene
  function

6
CHANGES IN CHROMOSOME STRUCTURE

• things to keep in mind
• each chromatid is has a single DNA molecule
• need either...
• 2 double strand breaks
• crossing over between repetative sequences
• chromosome breakage ? ends highly reactive
  (normal telomeres not)
• double strand breaks are lethal unless repaired
• repaired by joining broken ends

7
CHANGES IN CHROMOSOME STRUCTURE

• more things to keep in mind
• repair can restore original sequence or
• generate rearrangement
• acentric products are lost inviable
• dicentric products are broken inviable
• rearrangements can be
• spontaneous
• induced by radiation... X- or ?-rays
• mainly studied in heterozygotes

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CHANGES IN CHROMOSOME STRUCTURE

• 2 types of rearrangements
• unbalanced change gene dosage
• deletions
• uncover deleterious alleles ? usually lethal
• duplications
• extra material ? evolutionary divergence

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CHANGES IN CHROMOSOME STRUCTURE

• 2 types of rearrangements
• balanced change gene dosage
• inversions
• reduced fertility
• reduced recombination in inverted region
• translocations
• reorganizes linkage ? 50 sterility fertility
• novel linkage of genes on translocated
  chromosomes

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CHANGES IN CHROMOSOME STRUCTURE

• origins of rearrangements by 2 processes
• break / rejoining
• spontaneous
• radiation

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CHANGES IN CHROMOSOME STRUCTURE

• origins of rearrangements by 2 processes
• break / rejoining
• spontaneous
• radiation
• crossing over
• illegitimate

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CHANGES IN CHROMOSOME STRUCTURE

• visualization in heterozygotes
• strong pairing affinity during meiotic prophase I
• abnormal patterns seen in rearrangement
  heterozygotes (/)

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CHANGES IN CHROMOSOME STRUCTURE

• biological importance
• research tools ?
• new combinations of genes
• mapping
• recombination suppression
• mutant rescue
• applied research ? medicine agriculture
• evolutionary significance ? genome reshuffling

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CHANGES IN CHROMOSOME STRUCTURE

• deletions
• 1 chromosome break ? terminal
• 2 chromosome break ? interstitial

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CHANGES IN CHROMOSOME STRUCTURE

• deletions
• intragenic ? within 1 gene
• do not revert (? point mutations)
• can be viable if gene not vital
• multigenic ? gt 1 gene
• do not revert
• usually homozygous lethal
• sometimes heterozygous lethal

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CHANGES IN CHROMOSOME STRUCTURE

• deletions
• multigenic ? gt 1 gene
• uncovers recessive alleles on homologue
• pseudodominance
• deletion mapping

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CHANGES IN CHROMOSOME STRUCTURE

• deletions
• multigenic ? gt 1 gene
• uncovers recessive alleles on homologue
• pseudodominance
• deletion mapping

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CHANGES IN CHROMOSOME STRUCTURE

• deletions
• multigenic ? gt 1 gene
• deletion mapping linkage maps

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CHANGES IN CHROMOSOME STRUCTURE

• deletions
• multigenic ? gt 1 gene
• deletion mapping human disease, e.g. cri du
  chat syndrome

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CHANGES IN CHROMOSOME STRUCTURE

• duplications (2 chromosome breaks)
• adjacent, same order ? tandem
• adjacent, reverse order ? reverse

21
CHANGES IN CHROMOSOME STRUCTURE

• duplications
• intragenic ? within 1 gene
• do not revert (? point mutations, see below)
• can be viable if genetic balance not critical
• multigenic ? gt 1 gene
• do not revert (see below)
• homozygous lethal if genetic balance critical
• can be heterozygous lethal if balance critical

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CHANGES IN CHROMOSOME STRUCTURE

• duplications
• illegitimate recombination possible, e.g. Bar

23
CHANGES IN CHROMOSOME STRUCTURE

• duplications
• important for gene evolution, e.g. human
  hemoglobin genes

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CHANGES IN CHROMOSOME STRUCTURE

• duplications
• important for gene evolution, e.g. human
  hemoglobin genes

25
CHANGES IN CHROMOSOME STRUCTURE

• inversions
• does not include centromere ? paracentric
• does include centromere ? pericentric

26
CHANGES IN CHROMOSOME STRUCTURE

• inversions
• does not include centromere ? paracentric

A B C D E F G
H
27
CHANGES IN CHROMOSOME STRUCTURE

• inversions
• does not include centromere ? paracentric

A B C D E F G
H
28
CHANGES IN CHROMOSOME STRUCTURE

• inversions
• does not include centromere ? paracentric

A C B D E F G
H
29
CHANGES IN CHROMOSOME STRUCTURE

• inversions
• does include centromere ? pericentric

A B C D E F G
H
30
CHANGES IN CHROMOSOME STRUCTURE

• inversions
• does include centromere ? pericentric

A B C D E F G
H
31
CHANGES IN CHROMOSOME STRUCTURE

• inversions
• does include centromere ? pericentric

A B F E D C G
H
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CHANGES IN CHROMOSOME STRUCTURE

• inversions
• no change in total genetic material
• breakpoints can (but not always) disrupt genes
• no disruption ? viable homozygotes
• disruption ? heterozygotes only (majority)
• do not revert
• recombination in inversion ? segm. aneuploidy
• recombinant gametes lethal ?, fertility ?
• recombination suppression

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CHANGES IN CHROMOSOME STRUCTURE

• inversions
• breakpoints between genes

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CHANGES IN CHROMOSOME STRUCTURE

• inversions
• breakpoints between genes... disruption of 1

• breakpoints within genes... gene fusion

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CHANGES IN CHROMOSOME STRUCTURE

• inversions
• loops

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CHANGES IN CHROMOSOME STRUCTURE

• inversions
• loops

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CHANGES IN CHROMOSOME STRUCTURE

• inversions
• loops

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CHANGES IN CHROMOSOME STRUCTURE

• inversions
• crossing over in a paracentric inversion
  heterozygote

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CHANGES IN CHROMOSOME STRUCTURE

• inversions
• crossing over in a paracentric inversion
  heterozygote
• 1 normal ? viable
• 1 inversion ? viable
• 1 acentric ? lost
• 1 dicentric ? 2 lethal deletion products

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CHANGES IN CHROMOSOME STRUCTURE

• inversions
• crossing over in a pericentric inversion
  heterozygote

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CHANGES IN CHROMOSOME STRUCTURE

• inversions
• crossing over in a pericentric inversion
  heterozygote
• 1 normal ? viable
• 1 duplication ? lethal
• 1 deletion ? lethal
• 1 inversion ? viable

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CHANGES IN CHROMOSOME STRUCTURE

• translocations (reciprocal or Robertsonian)
• no change in total genetic material
• do not revert
• meiosis ? segmental aneuploidy
• lethality
• semi-sterility
• rearrangement of linkage groups
• can restructure genomes

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CHANGES IN CHROMOSOME STRUCTURE

• translocations
• heterozygotes
• adjacent-1 ? 4 lethal
• adjacent-2 ? rare, 4 lethal
• alternate ? 2 normal 2 carrier

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CHANGES IN CHROMOSOME STRUCTURE

• translocations
• pseudolinkage observed from test cross of
  translocation heterozygote a/ ab/b ? a/a b/b

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CHANGES IN CHROMOSOME STRUCTURE

• translocations
• position-effect variegation

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PROBLEMS

• 1-55 on pp. 512-520
• consider (read think about) all of the
  questions
• at the very least you should do s 22, 23, 26,
  40, 49