Transcript Basic genetics - Informatics: Indiana University

Basic genetics
Haixu Tang
School of Informatics
Mendel’s two innovations
• Developed pure lines
– a population that breeds true for a particular
trait
• Counted his results and kept statistical
notes
Phenotypes of Mendel's pea plants
•
•
•
•
round or wrinkled seed phenotype
yellow or green seed phenotype
red or white flower phenotype
tall or dwarf plant phenotype
Results from Mendel's
Experiments
Parental Cross
F1 Phenotype F2 Phenotypic Ratio
F2 Ratio
Round x Wrinkled
Seed
Round
5474 Round:1850
Wrinkled
2.96:1
Yellow x Green Seeds
Yellow
6022 Yellow:2001 Green
3.01:1
Red x White Flowers
Red
705 Red:224 White
3.15:1
Tall x Dwarf Plants
Tall
l787 Tall:227 Dwarf
2.84:1
Phenotypes
• Dominant - the allele that expresses itself at the
expense of an alternate allele; the phenotype
that is expressed in the F1 generation from the
cross of two pure lines
• Recessive - an allele whose expression is
suppressed in the presence of a dominant allele;
the phenotype that disappears in the F1
generation from the cross of two pure lines and
reappears in the F2 generation
Conclusion
•
•
•
•
The hereditary determinants are of a particulate
nature. These determinants are called genes.
Each parent has a gene pair in each cell for each trait
studied. The F1 from a cross of two pure lines contains
one allele for the dominant phenotype and one for the
recessive phenotype. These two alleles comprise the
gene pair.
One member of the gene pair segregates into a
gamete, thus each gamete only carries one member of
the gene pair.
Gametes unite at random and irrespective of the other
gene pairs involved.
Some terms
• Allele - one alternative form of a given allelic pair; tall and dwarf are
the alleles for the height of a pea plant; more than two alleles can
exist for any specific gene, but only two of them will be found within
any individual
• Allelic pair - the combination of two alleles which comprise the
gene pair
• Homozygote - an individual which contains only one allele at the
allelic pair; for example DD is homozygous dominant and dd is
homozygous recessive; pure lines are homozygous for the gene of
interest
• Heterozygote - an individual which contains one of each member of
the gene pair; for example the Dd heterozygote
• Genotype - the specific allelic combination for a certain gene or set
of genes
F1: Symbol representation
F2: Punnett Square
Union of Gametes
At Random
D
d
D
DD
(Tall)
Dd
(Tall)
d
Dd
(Tall)
dd
(Short)
Mendel's First Law
• The law of segregation: during gamete
formation each member of the allelic pair
separates from the other member to form
the genetic constitution of the gamete
Test the hypothesis
Genotype of the F2 individuals
Phenotypes
Genotypes Genetic Description
F2 Tall Plants
1/3 DD
2/3 Dd
F2 Dwarf Plants all dd
Pure line homozygote dominant
Heterozygotes
Pure line homozygote recessive
Thus the F2 is genotypically 1/4 Dd : 1/2 Dd : 1/4 dd
Backcross: Dd x dd
• The cross of an F1 hybrid to one of the
homozygous parents; for pea plant height
the cross would be Dd x DD or Dd x dd;
most often, though a backcross is a cross
to a fully recessive parent
Backcross One or (BC1) Phenotypes: 1 Tall : 1 Dwarf
BC1 Genotypes: 1 Dd : 1 dd
Monohybrid
• Monohybrid cross - a cross between
parents that differ at a single gene pair
(usually AA x aa)
• Monohybrid - the offspring of two parents
that are homozygous for alternate alleles
of a gene pair
• Remember --- a monohybrid cross is not
the cross of two monohybrids.
Variations to Mendel's First Law
of Genetics
• Codominance - a relationship among alleles where both
alleles contribute to the phenotype of the heterozygote
• Incomplete dominance - the F1 produces a phenotype
quantitatively intermediate between the two homozygous
parents;
Pedigree Analysis
Traits exhibiting dominant gene
action
• affected individuals have at least one
affected parent
• the phenotype generally appears every
generation
• two unaffected parents only have
unaffected offspring
Traits exhibiting recessive gene
action
• unaffected parents can have affected
offspring
• affected progeny are both male and
female
Mendel's Law of Independent
Assortment
We have followed the expression of only one
gene. Mendel also performed crosses in
which he followed the segregation of two
genes. These experiments formed the
basis of his discovery of his second law,
the law of independent assortment.
Dihybrid cross
• Dihybrid cross - a cross between two
parents that differ by two pairs of alleles
(AABB x aabb)
• Dihybrid- an individual heterozygous for
two pairs of alleles (AaBb)
Mendel’s experiment
• Parental Cross: Yellow, Round Seed x Green,
Wrinkled Seed
• F1 Generation: All yellow, round
• F2 Generation: 9 Yellow, Round, 3 Yellow,
Wrinkled, 3 Green, Round, 1 Green, Wrinkled
Seed Color: Yellow = G; Green = g
Seed Shape: Round = W; Wrinkled = w
Parental cross
Female Gametes
GW
GGWW
GW (Yellow,
round)
Gw
gw
GgWW
(Yellow,
round)
GgWw
(Yellow,
round)
Gw
GGWw GGww GgWw
(Yellow, (Yellow, (Yellow,
round) wrinkled) round)
Ggww
(Yellow,
wrinkled)
gW
GgWW
(Yellow,
round)
gw
GgWw
Ggww
ggWw
(Yellow, (Yellow, (Green,
round) wrinkled) round)
Male
Gametes
GGWw
(Yellow,
round)
gW
GgWw
(Yellow,
round)
ggWW
(Green,
round)
ggWw
(Green,ROUND)
ggww
(Green,
wrinkled)
Phenotype
General Genotype
9 Yellow, Round Seed
G_W_
3 Yellow, Wrinkled Seed
G_ww
3 Green, Round Seed
ggW_
1 Green, Wrinkled Seed
ggww
Mendel's Second Law - the law of
independent assortment
• During gamete formation the segregation
of the alleles of one allelic pair is
independent of the segregation of the
alleles of another allelic pair.
backcross - F1 dihybrid x
Female Gametes
Male
Gamet
es
gw
GW
Gw
gW
gw
GgWw
(Yellow,
round)
Ggww
(Yellow,
wrinkled)
ggWw
(Green,
round)
ggww
(Green,
wrinkled)
The phenotypic ratio of the test cross is:
•1 Yellow, Round Seed
•1 Yellow, Wrinkled Seed
•1 Green, Round Seed
•1 Green, Wrinkled Seed
The Chi-Square Test
• An important question to answer in any
genetic experiment is how can we decide
if our data fits any of the Mendelian ratios
we have discussed. A statistical test that
can test out ratios is the Chi-Square or
Goodness of Fit test.
Degrees of freedom (df) = n-1, where n is the number of classes
An example
Let's test the following data to determine if it fits a 9:3:3:1 ratio.
Observed Values
Expected Values
315 Round, Yellow Seed
(9/16)(556) = 312.75 Round, Yellow Seed
108 Round, Green Seed
(3/16)(556) = 104.25 Round, Green Seed
101 Wrinkled, Yellow Seed
(3/16)(556) = 104.25 Wrinkled, Yellow
32 Wrinkled, Green
556 Total Seeds
Number of classes (n) = 4
(1/16)(556) = 34.75 Wrinkled, Green
556.00 Total Seeds
df = n-1 + 4-1 = 3
Chi-square value = 0.47
A Chi-Square Table
Probability
Degrees
of
Freedom
1
2
3
0.9
0.02
0.21
0.58
0.5
0.46
1.39
2.37
0.1
0
.
0
5
0.01
2.71
3
.
8
4
6.64
4.61
5
.
9
9
9.21
6.25
7
.
8
2
11.35
9
Pleiotropic Effects and Lethal
Genes
• In 1904, a cross was made between a
yellow-coated mouse and a mouse with a
gray coat. The gray- coated mouse was
extensively inbred and therefore was
considered to be pure bred.
• Next a cross was made between two
yellow mice. What genetic ratio would we
expect to see? Yy x Yy should give a ratio
of 3 yellow:1 gray. The result, though, was
a ratio of 2 yellow to 1 gray mice. How
can this result be explained? Let's first
set up a Punnett Square.
Testcross
• All testcross data with the yellow mice give
a 1:1 ratio. This ratio is typical of what is
seen with heterozygous individuals.
• All of the yellow mice from the cross of two
heterozygous yellow mice are
genotypically Yy. Somehow the YY
genotype is lethal. The 2:1 ratio is the
typical ratio for a lethal gene.
Lethal gene
• Lethal Gene - a gene that leads to the
death of an individual; these can be either
dominant or recessive in nature.
• Pleiotropic gene - a gene that affects
more than one phenotype
Gene Interactions
Rose
Single
Pea
Walnut
Phenotypes
Genotypes
Frequency
Walnut
R_P_
9/16
Rose
R_pp
3/16
Pea
rrP_
3/16
Single
rrpp
1/16
Epistasis
• The interaction between two or more
genes to control a single phenotype
Modifier Genes
• Instead of masking the effects of another gene, a gene can modify
the expression of a second gene. In mice, coat color is controlled by
the B gene. The B allele conditions black coat color and is dominant
to the b allele that produces a brown coat. The intensity of the color,
either black or brown is controlled by another gene, the D gene. At
this gene, the dominant D allele controls full color whereas the
recessive d allele conditions a dilute or faded expression of the color
expression at the B gene. Therefore, if a cross is made among mice
that are BdDd, the following phenotypic distribution will be seen:
–
–
–
–
9 B_D_ (black)
3 B_dd (dilute black)
3 bbD_ (brown)
1 bbdd (dilute brown)
• The D gene does not mask the effect of the B gene, rather it
modifies its expression.
Gene linkage
• One experiment was performed by Bateson and
Punnett with sweet peas. They performed a
typical dihybrid cross between one pure line with
purple flowers and long pollen grains and a
second pure line with red flowers and round
pollen grains. Because they knew that purple
flowers and long pollen grains were both
dominant, they expected a typical 9:3:3:1 ratio
when the F1 plants were crossed.
Observed
Expected
Purple, long (P_L_)
284
215
Purple, round (P_ll)
21
71
Red, long (ppL_)
21
71
Red, round (ppll)
55
24
Total
381
381
Linked Genes On The Same
Chromosome
F1 Gamete
Testcross Distribution
Gamete Type
pr+ vg+
1339
Parental
pr+ vg
151
Recombinant
pr vg+
154
Recombinant
pr vg
1195
Parental
Coupling and repulsion
F1 Gamete
Testcross Distribution
Gamete Type
pr+ vg+
1339
Parental
pr+ vg
151
Recombinant
pr vg+
154
Recombinant
pr vg
1195
Parental
Genotype
Observed
Type of Gamete
ABC
390
Parental
abc
374
Parental
AbC
27
Single-crossover between genes C and B
aBc
30
Single-crossover between genes C and B
ABc
5
Double-crossover
abC
8
Double-crossover
Abc
81
Single-crossover between genes A and C
aBC
85
Single-crossover between genes A and C
Total
1000