Transcript Chapter 14. Mendel & Genetics

Mendel & Genetics
Gregor Mendel
• Modern genetics began in the
mid-1800s in an abbey garden,
where a monk named Gregor
Mendel documented inheritance
in peas
– used experimental method
– used quantitative analysis
• collected data & counted them
– excellent example of scientific
method
Mendel’s work
• Bred pea plants
– cross-pollinated true breeding parents (P)
– raised seed & then
observed traits (F1)
• filial
– allowed offspring
to cross-pollinate
& observed next
generation (F2)
Mendel collected data for 7 pea traits
Looking closer at Mendel’s work
P
true-breeding
true-breeding
X
purple-flower peas
white-flower peas
F1
100%
purple-flower peas
generation
(hybrids)
100%
self-pollinate
F2
generation
75%
25%
purple-flower peas white-flower peas
3:1
What did Mendel’s findings
mean?
• Traits come in alternative versions
– purple vs. white flower color
– alleles
• different alleles vary in the sequence of nucleotides
at the specific locus of a gene
purple-flower allele &
white-flower allele are
2 DNA variations at
flower-color locus
different versions of
gene on homologous
chromosomes
Traits are inherited as discrete
units
• For each characteristic, an organism
inherits 2 alleles, 1 from each parent
– diploid organism
• inherits 2 sets of chromosomes,
1 from each parent
• homologous chromosomes
• like having 2 editions of encyclopedia
– Encyclopedia Britannica
– Encyclopedia Americana
What did Mendel’s findings
mean?
• Some traits mask others
– purple & white flower colors are separate
traits that do not blend
• purple x white ≠ light purple
• purple masked white
– dominant allele
• fully expressed
– recessive allele
• no noticeable effect
• the gene makes a
non-functional protein
Genotype vs. phenotype
• difference between how an organism
“looks” & its genetics
– phenotype
• description of an organism’s trait
– genotype
• description of an organism’s genetic makeup
Explain Mendel’s results using
…dominant & recessive
…phenotype & gentotype
P
F1
Making crosses
• using representative letters
– flower color alleles  P or p
– true-breeding purple-flower peas  PP
– true-breeding white-flower peas  pp
PP x pp
Pp
Looking closer at Mendel’s work
P
true-breeding
true-breeding
X
purple-flower peas
white-flower peas
PP
pp
100%
purple-flower peas
F1
generation
(hybrids)
phenotype
100%
Pp Pp Pp Pp
self-pollinate
F2
generation
75%
25%
purple-flower peas white-flower peas
?
?
?
?
3:1
Punnett squares
Pp x Pp
male / sperm
P
p
%
genotype
PP
%
phenotype
25%
75%
Pp
female / eggs
50%
P
p
PP
Pp
Pp
pp
Pp
pp
25% 25%
1:2:1
3:1
Genotypes
• Homozygous = same alleles = PP, pp
• Heterozygous = different alleles = Pp
homozygous
dominant
homozygous
recessive
Phenotype vs. genotype
• 2 organisms can have the same
phenotype but have different genotypes
purple PP
homozygous dominant
purple Pp
heterozygous
Dominant phenotypes
• It is not possible to determine the
genotype of an organism with a dominant
phenotype by looking at it.
PP?
Pp?
Test cross
• Cross-breed the dominant phenotype —
unknown genotype — with a homozygous
recessive (pp) to determine the identity of
the unknown allele
x
is it
PP or Pp?
pp
Test cross
x
x
PP
P
pp
p
p
Pp
Pp
Pp
p
P
100%
P
Pp
Pp
p
pp
p
Pp
Pp
50%:50%
1:1
pp
pp
Mendel’s laws of heredity (#1) P
• Law of segregation
PP
– when gametes are produced during
meiosis, homologous chromosomes
separate from each other
pp
– each allele for a trait is packaged into
a separate gamete
P
p
p
P
Pp
p
Law of Segregation
• What meiotic event
creates the
law of segregation?
Meiosis 1
Monohybrid cross
• Some of Mendel’s experiments followed
the inheritance of single characters
– flower color
– seed color
– monohybrid crosses
Dihybrid cross
• Other of Mendel’s
experiments followed
the inheritance of 2
different characters
– seed color and
seed shape
– dihybrid crosses
Dihybrid cross
P
true-breeding
yellow, round peas
Y = yellow
R = round
generation
(hybrids)
F2
generation
x
YYRR
yyrr
y = green
r = wrinkled
yellow, round peas
F1
self-pollinate
true-breeding
green, wrinkled peas
100%
YyRr
9/16
yellow
round
peas
3/16
green
round
peas
3/16
1/16
yellow
green
wrinkled wrinkled
peas
peas
9:3:3:1
What’s going on here?
• How are the alleles on different
chromosomes handed out?
– together or separately?
YyRr
YR
yr
YyRr
YR
Yr
yR
yr
Dihybrid cross
YyRr x YyRr
YR
Yr
yR
yr
YR YYRR YYRr YyRR YyRr
Yr
YyRr
Yyrr
yR YyRR YyRr yyRR
yyRr
yr
YYRr
YyRr
YYrr
Yyrr
yyRr
yyrr
9/16
yellow
round
3/16
green
round
3/16
yellow
wrinkled
1/16
green
wrinkled
Mendel’s laws of heredity (#2)
• Law of independent assortment
– each pair of alleles segregates into gametes
independently
• 4 classes of gametes are produced
in equal amounts
– YR, Yr, yR, yr
• only true for genes on separate chromosomes
YyRr
Yr
Yr
yR
yR
YR
YR
yr
yr
Law of Independent Assortment
• What meiotic event
creates the
law of independent assortment?
Meiosis 1
The
chromosomal
basis of Mendel’s
laws…
Trace the genetic
events through
meiosis, gamete
formation &
fertilization to
offspring
Review: Mendel’s laws of
heredity
• Law of segregation
– monohybrid cross
• single trait
– each allele segregates into separate gametes
• established by Meiosis 1
• Law of independent assortment
– dihybrid (or more) cross
• 2 or more traits
– each pair of alleles for genes on separate
chromosomes segregates into gametes
independently
• established by Meiosis 1
Mendel chose peas wisely
• Pea plants are good for genetic research
– available in many varieties with distinct
heritable features with different variations
• flower color, seed color, seed shape, etc.
– Mendel had strict control over which plants
mated with which
• each pea plant has male & female structures
• pea plants can self-fertilize
• Mendel could also cross-pollinate plants: moving
pollen from one plant to another
Mendel chose peas luckily
• Pea plants are good for genetic research
– relatively simple genetically
• most characters are controlled by
a single gene
• each gene has only 2 alleles,
one of which is completely
dominant over the other
Any Questions??
Probability & Genetics
Genetics & Probability
• Mendel’s laws:
– segregation
– independent assortment
reflect same laws of probability
that apply to tossing coins or
rolling dice
Probability & genetics
• Calculating probability of
making a specific gamete is
just like calculating the
probability in flipping a coin
– probability of tossing heads?
50%
– probability making a P
gamete…
P
50%
Pp
p
PP
P
100%
P
Probability & genetics
• Outcome of 1 toss has no impact
on the outcome of the next toss
– probability of tossing heads each
time?
50%
– probability making a P gamete each
time?
50%
P
Pp
p
Calculating probability
Pp x Pp
male / sperm
P
p
sperm
egg
offspring
P
P
PP
P
p
1/2 x 1/2 =
female / eggs
1/2 x 1/2 =
P
PP
Pp
p
Pp
pp
Pp
1/4
P
1/2 x 1/2 =
p
1/4
1/4
1/2
p
p
1/2 x 1/2 =
pp
1/4
Rule of multiplication
• Chance that 2 or more independent
events will occur together
– probability that 2 coins tossed at the
same time will land heads up
1/2 x 1/2 = 1/4
– probability of Pp x Pp  pp
1/2 x 1/2 = 1/4
Calculating dihybrid probability
• Rule of multiplication also applies to
dihybrid crosses
– heterozygous parents — YyRr
– probability of producing yyrr?
• probability of producing y gamete = 1/2
• probability of producing r gamete = 1/2
• probability of producing yr gamete =
1/2 x 1/2 = 1/4
• probability of producing a yyrr offspring =
1/4 x 1/4 = 1/16
Rule of addition
• Chance that an event can occur
2 or more different ways
– sum of the separate probabilities
– probability of Pp x Pp  Pp
sperm
egg
offspring
P
p
Pp
1/2 x 1/2 =
p
P
1/2 x 1/2 =
1/4
Pp
1/4
1/4
+ 1/4
1/2
Chi-square test
• Test to see if your data supports
your hypothesis
• Compare “observed” vs. “expected” data
– is variance from expected due to
“random chance”?
– is there another factor influencing data?
• null hypothesis
• degrees of freedom
• statistical significance
Any Questions??
Beyond Mendel’s Laws
of Inheritance
Extending Mendelian genetics
• Mendel worked with a simple system
– peas are genetically simple
– most traits are controlled by a
single gene
– each gene has only 2 alleles, 1 of which is
completely dominant to the other
• The relationship between
genotype & phenotype
is rarely that simple
Incomplete dominance
• Heterozygotes show an intermediate
phenotype
– RR = red flowers
– R’R’ = white flowers
– RR’ = pink flowers
• make 50% less color
Incomplete dominance
P
X
true-breeding
red flowers
true-breeding
white flowers
100% pink flowers
F1
100%
generation
(hybrids)
self-pollinate
25%
red
F2
generation
50%
pink
25%
white
1:2:1
Incomplete dominance
CRCW x CRCW
female / eggs
male / sperm
CR
CW
CR
CW
CRCR
CRCW
%
genotype
CRCR
CRCW
%
phenotype
25% 25%
50% 50%
CRCW
CRC W
C WC W
C WC W
25% 25%
1:2:1
1:2:1
Co-dominance
• 2 alleles affect the phenotype in
separate, distinguishable ways
– ABO blood groups
– 3 alleles
• I A, I B, i
• both IA & IB are dominant to i allele
• IA & IB alleles are co-dominant to each other
– determines presences of
oligosaccharides on the
surface of red blood cells
Blood type
genotype
phenotype
__
type B
type B
oligosaccharides on
surface of RBC
__
type AB
both type A & type B
oligosaccharides on
surface of RBC
universal
recipient
type O
no oligosaccharides
on surface of RBC
universal
donor
IA i type A
IB IB
IB
IA IB
ii
status
type A
oligosaccharides on
surface of RBC
IA IA
i
phenotype
1901 | 1930
Blood compatibility
• Matching compatible blood groups
– critical for blood transfusions
• A person produces antibodies against
oligosaccharides in foreign blood
– wrong blood type
• donor’s blood has A or B oligosaccharide that is
foreign to recipient
• antibodies in recipient’s blood bind to foreign
molecules
• cause donated blood cells to clump together
• can kill the recipient
Karl Landsteiner
(1868-1943)
Blood donation
Pleiotropy
• Most genes are pleiotropic
– one gene affects more than one
phenotypic character
• wide-ranging effects due to a single gene:
• dwarfism (achondroplasia)
• gigantism (acromegaly)
Acromegaly: André the Giant
Pleiotropy
• It is not surprising that a gene can affect
a number of organism’s characteristics
– consider the intricate molecular & cellular
interactions responsible for an organism’s
development
• cystic fibrosis
– mucus build up in many organs
• sickle cell anemia
– sickling of blood cells
Epistasis
• One gene masks another
– coat color in mice =
2 genes
• pigment (C) or
no pigment (c)
• more pigment (black=B)
or less (brown=b)
• cc = albino,
no matter B allele
• 9:3:3:1 becomes 9:3:4
Epistasis in Labrador retrievers
• 2 genes: E & B
– pigment (E) or no pigment (e)
– how dark pigment will be: black (B) to brown (b)
Polygenic inheritance
• Some phenotypes determined by
additive effects of 2 or more genes on a
single character
– phenotypes on a continuum
– human traits
•
•
•
•
•
•
skin color
height
weight
eye color
intelligence
behaviors
Albinism
albino
Africans
Johnny & Edgar Winter
Nature vs. nurture
• Phenotype is controlled by
both environment & genes
Human skin color is influenced
by both genetics &
environmental conditions
Coat color in arctic
fox influenced by
heat sensitive alleles
Color of Hydrangea flowers
is influenced by soil pH
It all started with a fly…
• Chromosome theory of inheritance
– experimental evidence from improved
microscopy & animal breeding led us to a
better understanding of chromosomes &
genes
beyond Mendel
• Drosophila studies
A. H. Sturtevant in
the Drosophila
stockroom at
Columbia University
1910 | 1933
Thomas Hunt Morgan
• embryologist at Columbia University
– 1st to associate a specific gene with a specific
chromosome
– Drosophila breeding
•
•
•
•
prolific
2 week generations
4 pairs of chromosomes
XX=female, XY=male
Morgan’s first mutant…
• Wild type fly = red eyes
• Morgan discovered a mutant
white-eyed male
– traced the gene for eye color to
a specific chromosome
Discovery of sex linkage
red eye
female
x
white eye
male
all
red eye
offspring
75%
red eye
female
x
25%
white eye
male
How is this possible?
Sex-linked trait!
Sex-linked traits
• Although differences between women &
men are many, the chromosomal basis of
sex is rather simple
• In humans & other mammals, there are 2
sex chromosomes: X & Y
– 2 X chromosomes develops as
a female: XX
• redundancy
– an X & Y chromosome develops as
a male: XY
• no redundancy
Sex chromosomes
autosomal
chromosomes
sex
chromosomes
Genes on sex chromosomes
• Y chromosome
– SRY: sex-determining region
• master regulator for maleness
• turns on genes for production of
male hormones
– pleiotropy!
• X chromosome
– other traits beyond sex determination
• hemophilia
• Duchenne muscular dystrophy
• color-blind
Human X chromosome
• Sex-linked
– usually
X-linked
– more than 60
diseases
traced to
genes on X
chromosome
Map of Human Y chromosome?
• < 30 genes on
Y chromosome
SRY
Sex-linked traits
H Xh x X
HY
HH
XHh
sex-linked recessive
XH
female / eggs
male / sperm
XH
XH
Y
XH XH
XH Y
XH Xh
Xh
XH
Xh
XH Xh
XhY
XHY
Y
Sex-linked traits summary
• X-linked
– follow the X chromosomes
– males get their X from their mother
– trait is never passed from father to son
• Y-linked
– very few traits
– only 26 genes
– trait is only passed from father to son
– females cannot inherit trait
X-inactivation
• Female mammals inherit two X
chromosomes
– one X becomes inactivated during embryonic
development
• condenses into compact object = Barr body
X-inactivation & tortoise shell
cat
• 2 different cell lines in cat
Male pattern baldness
• Sex influenced trait
– autosomal trait influenced by sex hormones
• age effect as well: onset after 30 years old
– dominant in males & recessive in females
• B_ = bald in males; bb = bald in females
Mechanisms of inheritance
• What causes the differences in alleles of a
trait?
– yellow vs. green color
– smooth vs. wrinkled seeds
– dark vs. light skin
– Tay sachs disease vs. no disease
– Sickle cell anemia vs. no disease
Mechanisms of inheritance
• What causes dominance vs. recessive?
– genes code for polypeptides
– polypeptides are processed into proteins
– proteins function as…
• enzymes
• structural proteins
• hormones
How does dominance work:
enzyme
= allele coding for
= allele coding for
functional enzyme
non-functional enzyme
= 50% functional enzyme
• sufficient enzyme present
• normal trait is exhibited
• NORMAL trait is DOMINANT
carrier
= 100% non-functional enzyme
• normal trait is not exhibited
aa
= 100% functional enzyme
• normal trait is exhibited
AA
Aa
How does dominance work:
structure
= allele coding for
= allele coding for
functional structural
protein
non-functional structural
protein
= 50% functional structure
• 50% proteins malformed
• normal trait is not exhibited
• MUTANT trait is DOMINANT
Aa
= 100% non-functional structure
• normal trait is not exhibited
AA
= 100% functional structure
• normal trait is exhibited
aa
Prevalence of dominance
• Because an allele is dominant
does not mean…
– it is better
– it is more common
Polydactyly:
dominant allele
Polydactyly
individuals are born with
extra fingers or toes
dominant to the recessive
allele for 5 digits
recessive allele far more
common than dominant
 399 individuals out of 400
have only 5 digits
 most people are homozygous
recessive (aa)
Hound Dog Taylor
Any Questions??
Studying Inheritance
in Humans
Pedigree analysis
• Pedigree analysis reveals Mendelian
patterns in human inheritance
– data mapped on a family tree
= male
= female
= male w/ trait
= female w/ trait
Genetic counseling
• Pedigree can help us understand the
past & predict the future
• Thousands of genetic disorders are
inherited as simple recessive traits
– benign conditions to deadly diseases
– albinism
– cystic fibrosis
– Tay sachs
– sickle cell anemia
– PKU
Genetic testing
Recessive diseases
• The diseases are recessive because the
allele codes for either a malfunctioning
protein or no protein at all
– Heterozygotes (Aa)
• carriers
• have a normal phenotype because one “normal”
allele produces enough of the required protein
Heterozygote crosses
• Heterozygotes as carriers of recessive alleles
Aa x Aa
female / eggs
male / sperm
A
A
a
AA
AA
Aa
Aa
A
Aa
a
A
a
Aa
Aa
aa
Aa
a
Cystic fibrosis
• Primarily whites of
European descent
– strikes 1 in 2500 births
• 1 in 25 whites is a carrier (Aa)
normal lung tissue
– normal allele codes for a membrane protein that
transports Cl- across cell membrane
• defective or absent channels cause high
extracellular levels of Cl• thicker & stickier mucus coats around cells
• mucus build-up in the pancreas, lungs, digestive tract &
causes bacterial infections
– without treatment children die before 5;
with treatment can live past their late 20s
Normal Lungs
Clairway
Na+
cells lining lungs
mucus secreting glands
Chloride channel
Transports chloride
through protein channel
out of cell.
Osmotic effects:
H2O follows Cl-
damaged lung tissue
Cystic fibrosis
Clairway
Na+
cells lining lungs
thickened mucus
hard to secrete
bacteria & mucus
build up
Tay-Sachs
• Primarily Jews of eastern European
(Ashkenazi) descent & Cajuns
– strikes 1 in 3600 births
• 100 times greater than incidence among
non-Jews or Mediterranean (Sephardic) Jews
– non-functional enzyme fails to breakdown
lipids in brain cells
• symptoms begin few months
after birth
• seizures, blindness &
degeneration of motor &
mental performance
• child dies before 5yo
Sickle cell anemia
• Primarily Africans
– strikes 1 out of 400 African Americans
– caused by substitution of a single amino acid
in hemoglobin
– when oxygen levels are low, sickle-cell
hemoglobin crystallizes into long rods
• deforms red blood cells into
sickle shape
• sickling creates pleiotropic
effects = cascade of other
symptoms
Sickle cell anemia
• Substitution of one amino acid in
polypeptide chain
Sickle cell phenotype
• 2 alleles are codominant
– both normal & abnormal hemoglobins are
synthesized in heterozygote (Aa)
– carriers usually healthy, although some suffer
some symptoms of
sickle-cell disease
under blood oxygen
stress
• exercise
Heterozygote advantage
• Sickle cell frequency
– high frequency of heterozygotes
is unusual for allele with severe
detrimental effects in homozygotes
• 1 out of 400 African Americans
• Suggests some selective advantage of being
heterozygous
– sickle cell: resistance to malaria?
– cystic fibrosis: resistance to cholera?
Heterozygote advantage
• Malaria
– single-celled eukaryote parasite spends part of its
life cycle in red blood cells
• In tropical Africa, where malaria is common:
– homozygous normal individuals die of malaria
– homozygous recessive individuals die of sickle cell
anemia
– heterozygote carriers are relatively free of both
• High frequency of sickle
cell allele in African
Americans is vestige of
African roots••••••
Malaria
Prevalence of Malaria
Prevalence of Sickle
Cell Anemia
Genetics & culture
• Why do all cultures have a taboo against incest?
– laws or taboos forbidding marriages between close
relatives are fairly universal
• Fairly unlikely that 2 carriers of same rare
harmful recessive allele will meet & mate
– but matings between close relatives increase risk
• consanguineous matings
– individuals who share a recent common ancestor are
more likely to carry
same recessive alleles
A hidden disease reveals itself
Aa
x
Aa
male / sperm
male / sperm
A
A
A
a
A
AA
AA
A
AA
Aa
a
Aa
Aa
a
Aa
aa
female / eggs
female / eggs
AA x Aa
Any Questions??