Viability in Human Aneuploidy

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Chapter 6

• Part 2

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Viability in Human Aneuploidy

• 2 other syndromes survive to term
• Patau 47,13
• Edwards 47,18
• Both have severe malformations and early
  lethality
• Realize that there are many other aneuploid
  conditions but fetus doesnt survive, see in
  fetus karyotype (15-20 spontaneous abortions)
• see 45,X in many aborted fetuses, 2n1 is more
  common so thought 2n-1 aborts very early
• Appears that we require a precise diploid
  complement of chromosomes to maintain delicate
  balance of genetic information expression

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Polyploidy

• More than 2 haploid sets of chromosomes are
  present prevalent in plants
• triploid 3n tetraploid 4n pentaploid 5n
• relatively infrequent in animals, occurs in
  lizards, amphibians, fish
• common in plants but not in plants that rely
  strictly on sexual reproduction for propagation

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2 Ways to Originate

• Addition of 1 or more sets of chromosomes,
  identical to haploid set of same species
  autopolyploidy
• Combination of chromosome sets from different
  species consequence of hybridization
  allopolyploidy
• A haploid set a1a2a3 .an with a
  being individual chromosomes and ntotal haploid
  number
• diploid organism is AA

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Autopolyploid

• Each additional set is identical to parent
• Arise by 1) failure to split during meiosis and
  fertilized by haploid gamete or 2) rarely 2 sperm
  may fertilize ovum
• Autotetraploids that are 4n are more apt to be
  seen in nature because they can produce even
  gametes

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Lab Created Autopolyploids

• Use colchicine, a drug that alters spindle
  formation, do not get separation during anaphase
• Remove the drug and the cell re-enters interphase
  creating a 4n cell
• Cell is larger than usual and in the plant world
  we see larger flowers and fruit useful in
  horticulture and commercial agriculture

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Commercial Autopolyploids

• Triploids some potatoes, Winesap apples,
  bananas, seedless watermelon, cultivated tiger
  lily
• Tetraploids alfalfa, coffee, MacIntosh apples,
  peanuts all have economic value
• Octaploids commercially produced strawberries

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Allopolyploidy

• 2 closely related species hybridized may not be
  able to generate viable gametes sterile
• chromosomes cannot synapse make appropriate
  gametes
• If the chromosomes can synapse, then get fertile
  tetraploid after chromosomal doubling
  allotetraploid
• usually called amphidiploid

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Seen in Plants

• If balanced gametes are formed then meiosis
  occurs naturally
• American cotton amphidiploid
• 13 large and 13 small chromosomes
• crossed Old World cotton to wild American cotton,
  treat with colchicine and make a new fertile
  variety
• see traits of both parents

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Variation in the Chromosome

• Structural changes in the chromosome can take
  many forms deletion, add or rearrange
  substantial parts of 1 or more chromosomes
• Deletions or duplications of genes or parts of
  chromosome
• Rearrangement inverted segments, exchange
  between non-homologous chromosome translocation
• occurs with breaks in chromosomes cause loss or
  rearrangement may increase due to exposure to
  chemicals or radiation

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Creating the Variation

• Ends of broken DNA ends are sticky and will join
  with another sticky end
• Heterozygous for aberration if in only one
  homolog, pattern helps in identifying change
• no loss or gain likely to be unaffected in
  hetreozygocity may be carriers however

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Deletions

• Missing region in the chromosome
• May occur at the end of the chromosome (terminal
  deletion) or in the midportion of chromosome
  (intercalary deletion)
• Portion with the centromere will undergo meiosis
  or mitosis but the other fragment may be lost

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Deletion or Compensation Loop

• During synapse the normal chromosome will need
  to form loop
• Even a small deletion can be detrimental so large
  deletions are usually lethal

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Duplication

• See a repeated segment of chromosome
• may be a single locus or a large portion present
  more than 1 time
• Occurs due to un-equal crossing over or error in
  DNA replication before meiosis
• in un-equal crossing over we can have a deletion
  and a duplication at the same time

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Gene Redundancy

• Usually relates to the rRNA genes
• Some gene products are required in every cell of
  an organism
• rRNA need enough of this transcript to make the
  large amount of ribosomes needed for protein
  synthesis during development
• have multiple copies of the genes in rDNA
• 7 copies in E. coli, 130 copies in Drosophilia
• See this with other genes as well

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Amplification

• Oocytes require even more rRNA than other cells
  in so actually stockpile ribosomes in the
  cytoplasm gene amplification
• Genes coding for rRNA are in the nucleolar
  organizing region (NOR) associated with the
  nucleolus where ribosomes are formed
• in frogs, may see 400 genes to make rRNA
• rDNA is selectively amplified to increase the
  rRNA even more each acting like a
  mini-nucleolus
• 1500 copies of the 400 genes 600,000 copies
  /cell
• each copy transcribed 20 times 12 million
  ribosomes/egg

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Bar Mutation in Drosophila

• Flies have slitlike eyes rather than oval eyes
  not a mutation
• B/B have 800 facets to eyes, B/B have 350, B/B
  have about 70 and some have even fewer and are
  called double-bar
• In section 16A on X chromosome duplicated in
  the Bar flies and 3 copies seen in double Bar
  flies
• duplication

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Role of Gene Duplication in Evolution

• 1970 Ohno hypothesized that new genes and gene
  functions came from gene duplication
• If the gene is in duplicated form, then if
  mutations made in it, these do not impact the
  organism overly much as they have a normal
  version of the gene
• eventually the gene has accumulated enough
  mutations that it may change the function may
  impart adaptive advantage to the organism
• see genes with similar sequence but different
  functions
• typsin/chymotrypsin Hgb/myoglobin
• Gene Families groups of contiguous genes whose
  products perform same function DNA homology
• human Hgb, T-cell receptors and Antigens on major
  histocompatibility complex (MHC)

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Inversions

• Rearrangement of the linear gene sequence
  segment of chromosomes turned around 180 in
  chromosomes
• no loss of genetic information
• breaks occur in 2 points and then reisert
• short or long with (pericentric inversion) and
  without (paracentric inversion) centromere
• May have little impact on individuals but
  interesting to geneticist