News Flash

1
News Flash

• Recent research on the pinot noir grape reveals
  that this organism has about 30,000 genes, more
  than the 20-25,000 found in humans.
• Outdone by a grape!

2
Chromosomal mutations

• A mutation is a change in the DNA
• Generally, mutations are considered at the gene
  level, but some types of mutations involve
  addition, loss, or change of DNA at the
  chromosomal level.
• We basically consider two types of change
• Change in chromosome number
• Change in chromosome structure

3
Changes in chromosome structure

• Deletions
• part is missing.
• Duplications
• extra piece
• Inversions
• section is flipped
• Translocations
• piece attached to another chromosome.

www.slh.wisc.edu/.../Partials/ CoMApr98part.html
ghr.nlm.nih.gov/ghr/info/ img,Duplication
4
Deletions are bad

• Deletions mean that DNA is missing
• whatever genes were in that region are gone
• if two copies are needed, theres trouble
• If the remaining allele is lethal, theres
  trouble
• the bigger the deletion, the more likely it will
  be serious.
• Deletions often accompany duplications
• Duplications are caused by unequal crossing over
• if some chromosome gets 2, another gets 0

5
Duplications
Part of chromosome is doubled visible in the
banding pattern. Duplication can increase gene
dosage this is usually harmful. Duplications
often caused by unequal crossing over
ghr.nlm.nih.gov/ghr/info/ img,Duplication
6
Red-green color blindness

• X-linked trait thus shows up much more often in
  males.
• Genes for red and green vision are related to
  rhodopsin, are very similar to each other, and
  probably arose from a duplication event.
• Because they are similar they sometimes line up
  with each during meiosis, causing unequal
  crossing over.

Crossing over can also occur in the middle of a
gene, causing partial color blindness.
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Duplications can be bad

• Bar eye in Drosophila
• Flies heterozygous for a duplicated gene have a
  bar shaped eye instead of a normal one
• Have 3 alleles total, the normal the duplicate
• Flies homozygous for this mutation (and thus have
  2 extra copies of the gene) have a very small
  undeveloped eye.
• Gene dosage issue.

http//www.usask.ca/biology/genetics/Gene_Action/b
ar-eye.jpg
8
Inversions
A portion of the chromosome is flipped relative
to the rest. Most of the problems with inversion
are due to complicated attempts by chromosomes to
pair up properly during meiosis. See next slide.
http//www.dynagene.com/images/in10ideo.gif
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Paracentric and pericentric inversions
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Problems with inversions in meiosis
Duplications, deletions, and dicentric and
acentric chromosomes can result from funny
pairing and subsequent crossing over.
www.mun.ca/.../Drosophila_inversion_loop.htm
11
Translocations
A piece of a chromosome winds up attached to
another chromosome. Could be a swap (reciprocal)
or not.
Translocations occur between non-homologous
chromosomes! Major problem is again pairing of
chromosomes during meiosis, resulting in extra or
missing pieces, leading to partial monosomies and
trisomies. Semi-sterility only some gametes good
http//library.thinkquest.org/18258/media/transloc
ation.gif
12
Non-reciprocal translocations
Piece of one chromosome breaks off, attaches to
another chromosome. Creates partial trisomies,
monosomies, which are generally
fatal.Robertsonian translocation fusion of
chromosomes near the centromere. One animation
shows two centromeres, the other shows none.
Definition describes fusion of centromeres. http/
/www.pdx.edu/newmanl/Robertsonian.gif http//www.
tokyo-med.ac.jp/genet/chm/rst.gif
Cases of inherited Down syndrome involve
translocation of part of Chromosome 21 to,
typically, 14.
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Rings, dicentrics, acentrics

• Chromosomes with damage can circularize
• Ring chromosomes result from radiation damage
• Dicentrics and acentrics
• Radiation damage or crossing over between
  chromosomes that are inverted.

www.lumc.nl/1050/research/Molecular_Cytogenet...
http//www.uic.edu/classes/bms/bms655/gfx/figure
10.gif
14
Mutations

• Mutations are inheritable changes in the DNA
• Failure to faithfully store genetic information
• Changes can be to chromosomes or genes
• Current focus changes to DNA sequences.
• This means an alteration in a basepair or
• in the order of the basepairs.

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Types of mutations-1

• Mutations can be classified in many, many ways
• Some ways mutually exclusive, some not.
• Spontaneous vs. Induced
• Spontaneous happens naturally
• Enzymatic errors, especially in copying
• Various chemical reactions
• Induced mutations specifically caused, as by
  researcher
• Treatment with various chemicals, radiation
• Gametic (germ line) vs. somatic
• Gametic mutations can be passed on to next
  generation
• Somatic only affects individual (in metazoans)

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Types of mutations-2How the mutations are
observed

• Morphological
• Change in physical structure, readily observed
• Nutritional/biochemical
• Mutated enzyme results in phenotypic change
• Bacterial auxotrophs sickle cell anemia
• Behavioral mutations
• Regulatory mutations
• Affect control of gene expression rather than
  protein

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Types of mutations-3

• Lethal mutations not easily studied unless
• Conditional mutations expressed depending on
  environmental conditions, especially temperature.
• a way to study lethal mutations permissive and
  restrictive temperatures esp. useful with
  bacteria
• temp sensitive mutations occur
• naturally, continued in offspring
• Siamese cats, Himalayan rabbits

www.tcainc.org/photos/ farpoint/saavik1.jpg
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Types of mutations-4

• Classification of mutations by FUNCTION
• Loss of function knockout or null.
• Hypomorphic lowered expression, leaky
• Hypermorphic greater activity or more visible
  trait
• typically regulatory mutation, results in
  increased expression
• Gain of function e.g. new enzymatic activity
• a factor in evolution
• Dominant negative bad apple spoils the bunch
  e.g. bad protein in multicomponent enzyme

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Detection of mutations

• Bacteria and fungi
• Prototrophs and auxotrophs microbe no longer
  able to synthesize or breakdown particular
  nutrient.
• Change in behavior, e.g. motility
• Various methods in plants and animals
• Humans (not suitable experimental organisms)
• Reliance on pedigrees
• Possible to determine sex linkage, dominance

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Mutations are rare (but not equally so)

• Mutation rate depends on species and on gene
• Generally, mutations are random
• Hot spot a location in DNA where mutations occur
  significantly more often than the usual 1/ 106.
• Monotonous run of single nucleotide or tandem
  repeats GGGGGGGGG or ATGGATGGATGG
• Methylated cytosines
• methylation is adding a CH3 group to something
• Cytosines are methylated to help indicate which
  DNA strand is older (helps with DNA repair).
• Problem occurs when a cytosine is chemically
  damaged by deamination. (more later)

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Mutations

• Our example
• information, 3 letters at a time, read
  consecutively
• Point mutations
• Frameshift mutations Insertion

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more Mutations

• Frameshift deletion
• Transposon mutagensis transposons are segments
  of DNA that can jump into another spot in the
  DNA they have information.

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More types of mutations

• Switch between A G, or C T transition
• Switch between purine and pyrimidine
  transversion
• Silent 3rd position of codon usually means same
  amino acid, so change here has no effect.
• Missense typically a single nucleotide change,
  causes change in amino acid and noticeable
  effect.
• Nonsense change amino acid codon to STOP codon
• Additions, deletions, and stuttering
• Stuttering repeated sequences sometimes copied
  incorrectly enzyme gets confused?