Download Lecture 8 Quantitative Genetics Quantitative Genetics

Lecture 8
Quantitative Genetics
CAPMBELL BIOLOGY Chapter 9
Quantitative Genetics
  How many genes affect a given phenotypic trait e.g. skin color?
or How many genes account for the observed variation in a trait?
and
  If its more than one gene what is the relative contribution of each?
There are two kinds of variation
Physical traits (phenotypes) can show two types of variation
a. Discrete variation
b. Continuous variation
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1.  Discrete Variation
  The variation shows widely different alternative states
  Most of the traits we ve so far encountered show discrete
variation
e.g. Seed shape in pea:
either round or wrinkled
Wing size in Drosophila
either wild-type or vestigial
Hemophilia in man
either normal or hemophiliac
Flower color in pea
either purple or white
Blood groups in man
a person has either one blood group or another:
A
B
AB
O
Discrete variants are inherited as simple Mendelian traits
This kind of variation is caused by the existence of
different alleles of a single gene (or locus)
  There may be two or more alternative alleles:
e.g. Human blood groups - One locus but 3 alleles: A, B, O
Possible genotypes
Phenotypes i.e. Blood group
AA
A
AO
A
BB
B
BO
B
AB
AB
OO
O
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2. Continuous Variation
The variation does not show a few discrete alternative states
but is found as a continuum in a population
e.g.
Height in Humans
Skin colour
Milk yield in cattle
IQ (intelligence quotient)
Time to run 100m
Weight in humans
Traits that show continuous variation are often referred to as
Quantitative Traits
They are called quantitative because they can be given a
numerical value e.g. Milk Yield
gallons/cow/year
Quantitative traits can typically have any value in a wide range
i.e. the value shows continuous variation within that range
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  Quantitative traits often show large environmental effects
e.g. Human height potential is affected by nutritional status in
early childhood
Skin colour is affected by exposure to sunlight
  Question: Are quantitative traits inherited and if so, how?
  Answer: Yes, to a greater or lesser extent depending on the
trait
This kind of inheritance is called:
Quantitative inheritance or Polygenic inheritance
Polygenic because typically many genes are involved in
determining the value of a quantitative trait
  Does the way in which Quantitative Traits are inherited differ
from the way in which discrete traits are inherited?
  Answer: No! Quantitative Traits are inherited like any other trait
  1920 s Edward East investigated the inheritance of:
Flower tube length in tobacco plants
He decided to cross plants of two different strains:
Strain A Short flower tube length 37 – 43 mm
Strain B Long flower tube length 91 – 97 mm
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Strain A
37 – 43mm
X
Strain B
91 – 97 mm
F1 progeny
No.
plants
narrow range
61 – 67 mm
61 64 67
Flower length
wide range
52 – 82 mm
F2 progeny
52
67
82
From the F2 population, he then selected individuals representing
the mean length and the extremes (longest and shortest)
and selfed them
shortest
54 X 54
mean
70 X 70
longest
82 X 82
F3
56
68
84
56 68 84
Flower tube length
56
68
84
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From these experiments we can conclude:
  Flower tube length in the parental strains A and B shows
continuous variation
  The final length values achieved shows wide variation:
37mm (shortest strain A) – 97mm (longest strain B)
  F1 progeny show an intermediate range: 61 – 67mm (mean: 64)
  F2 progeny show a very broad range:
52 – 82mm (mean: 67)
Although the range in values has broadened in the F2 population
the mean length in the F1 and F2 populations is very similar
  F3 progeny: parents with longer (or shorter) flowers have
offspring that have longer (or shorter) flowers
Lots of other
traits in plants and
animals are inherited
in the same way – here
is another example
in plants
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  Since the F3 populations show length values that are similar
to their F2 parents, it is clear that length is inherited
  How can we account for the continuous variation observed in
trait that shows Quantitative Inheritance?
  Propose that the trait shows continuous variation because it is
determined by several genes and that they have additive effects
Skin pigmentation shows enormous variation across the human
species
How can this be explained genetically?
  Evidence suggests that at least 3 genes A, B, C determine the
level of pigmentation
 A hypothesis to explain inheritance of skin pigmentation
1. Imagine that for each gene there are 2 alleles: Gene A: A or a
Gene B: B or b
Gene C: C or c
2. For each gene, one of the alleles (the dark skin allele)
is incompletely dominant and has an additive effect of
+1
3. The other allele is recessive ( a, b, and c) and has no effect i.e. 0
4. All the alleles that have an additive effect (i.e. A or B or C)
are given the same value +1
5. Environmental factors (e.g. exposure to sunlight) also has a
substantial effect on the final quantitative value of the trait
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There are therefore two possible extremes of pigmentation:
  An individual homozygous for the dominant alleles of each
gene:
AA B B C C
+1 +1 +1 +1 +1+1
will have a phenotype that expresses 6 units of darkness and will
have the darkest skin colour
An individual homozygous for all the recessive alleles of each
gene:
aa bb cc
Because each recessive allele contributes nothing toward skin
colour these individuals will have the lightest skin colour
  Individuals that are heterozygous for each gene (assume genes
are unlined): A, a B, b C, c express 3 units of darkness &
have an intermediate skin colour
Each individual will produce 8 types of gamete (ABC, aBC, abC,
AbC, ABc, aBc, Abc, abc)
  A large population where most individuals are heterozygous for
each of the 3 genes will produce offspring that have:
8 x 8 = 64 possible combinations of the alleles
The phenotype of the offspring will have all possible unit values
between 0 and 6
  This population will show continuous variation in skin colour
and the quantitative values will show what is called a
normal distribution in the population
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20/64
Fraction 15/64
of the
population
6/64
1/64
0
1
2
3
4
5
6
units
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Using brain-imaging the team
in UCLA show that the integrity
of the myelin deposits which are
found surrounding nerve fibres in
brain can in part determine the speed
with which information is signalled
and therefore processed. The faster
the signalling, the faster the
processing of information.
Our genetics can exert some
influence on our intelligence by
determining how well our nerve
axons are encased in myelin sheaths.
Chiang et al. 2009 J Neuroscience 29: 2212
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The team in UCLA
scanned the brains of 23
sets of identical twins &
23 sets of fraternal twins.
Identical twins are 100%
genetically the same, whereas
fraternal twins are 50%
similar.
The team found that there
was evidence that myelin
integrity was determined
genetically in many parts of
the human brain which can
influence intelligence. In
essence it was more similar
identical twins.
Of course there are lots of
other factors that influence
intelligence some of which
are environmental so this is just
part of the story
Chiang et al. 2009 J Neuroscience 29: 2212
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A genome-wide association study for coronary artery
disease identifies a novel susceptibility locus in the major
histocompatibility complex.
Davies RW, Wells GA, Stewart AF, Erdmann J, Shah SH,
Ferguson JF, Hall AS, Anand SS, Burnett MS, Epstein
SE, Dandona S, Chen L, Nahrstaedt J, Loley C, König IR,
Kraus WE, Granger CB, Engert JC, Hengstenberg C,
Wichmann HE, Schreiber S, Tang WH, Ellis SG, Rader
DJ, Hazen SL, Reilly MP, Samani NJ, Schunkert H,
Roberts R, McPherson R.
Circ Cardiovasc Genet. 2012 Apr 1;5(2):217-25. Epub 2012
Feb 7.
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