Transcript Polygenic Traits

Chromosomal mutations
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• 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
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
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Deletions are bad
• Deletions mean that DNA is missing
– whatever genes were in that region are gone
– if two copies are needed, there’s trouble
– If the remaining allele is lethal, there’s 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
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Duplications
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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
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
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• 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/bareye.jpg
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 your text and 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
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Translocations
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A piece of a chromosome winds up attached to another
chromosome. Could be a swap (reciprocal) or not.
Translocations occur between nonhomologous 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/translocation.gif
Non-reciprocal translocations
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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.
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/figure10.gif
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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
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• 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)
Types of mutations-2
How 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
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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
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)
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• 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)
Mutations
• Our example:
– information, 3 letters at a time, read consecutively
• Point mutations:
• Frameshift mutations: Insertion
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more Mutations
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• Frameshift: deletion
• Transposon mutagensis: transposons are segments
of DNA that can jump into another spot in the DNA;
they have information.
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?
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