Download Mendelian Genetics

Mendelian Genetics
Simple Probabilities & a Little Luck
Genetics
• the study of heredity & its mechanisms
• Gregor Mendel
– reported experimental results in 1865/66
– rediscovered in 1903 by de Vries, Correns &
von Tschermak
Genetics
• Before Mendel, heredity was seen as
– the blending of parental contributions
– unpredictable
• Mendel demonstrated that heredity
– involves distinct particles
– is statistically predictable
Cross pollination
Figure 10.1
Mendel’s Experiments
• the model system
– garden pea varieties
• easy to grow
• short generation time
• many offspring
• bisexual
–reciprocal cross-pollination
• self-compatible
–self-pollination
Mendel’s Experiments
• garden pea varieties
– many variable characters
• a character is a heritable feature
–flower color
• a trait is a character state
–blue flowers, white flowers, etc.
• a heritable trait is reliably passed down
• a true-breeding variety produces the same
trait each generation
7
characters,
14
traits
Table 10.1
one of Mendel’s characters
Figure 10.2
Mendel’s Experiments
• Mendel’s experimental design
– selected 7 characters with distinct traits
– crossed plants with one trait to plants with
the alternate trait (P = “parental” generation)
– self-pollinated offspring of P (F1 = first filial
generation)
– scored traits in F1 and F2 generations
Mendel’s Experiments
• Mendel’s experimental design
– Protocol #1: monohybrid crosses
• parents were true-breeding for alternate
traits of one character
• parents were reciprocally cross-pollinated
• F1 progeny were self-pollinated
• traits of F1 & F2 progeny were scored
Mendel’s Experiments
• Mendel’s experimental design
– Protocol #1: monohybrid crosses
– Results
• all F1 progeny exhibited the same trait
• F2 progeny exhibited both parental traits
in a 3:1 ratio (F1 trait: alternate trait)
Mendel’s Experiments
• Mendel’s experimental design
– Protocol #1: monohybrid crosses
– Analysis
• F1 trait is dominant
• alternate trait is recessive
–disappears from the F1 generation
–reappears, unchanged, in F2
– Relevance
• all seven characters have dominant and
recessive traits appearing 3:1 in F2
seven traits were inherited similarly
Table 10.1
Mendel’s
interpretation:
inheritance
does not
involve
blending
Figure 10.3
Mendel’s Experiments
• Mendel’s experimental design
– Protocol #1: monohybrid crosses
– Interpretation
• inheritance is by discrete units (particles)
• hereditary particles occur in pairs
• particles segregate at gamete formation
• particles are unaffected by combination
• =>Mendel’s particles are genes <=
Mendel’s Experiments
• Mendel’s experimental design
– Protocol #1: monohybrid crosses
• symbolic representation
–P: SS x ss
–F1: Ss
• each parent packages one gene in each
gamete
• gametes combine randomly
recessive
traits
disappear
in the
F1
generation
Figure 10.4
Mendel’s Experiments
• Mendel’s experimental design
– Protocol #1: monohybrid crosses
• [terminology
–different versions of a gene = alleles
–two copies of an allele = homozygous
–one copy of each allele = heterozygous
–genetic constitution = genotype
–round or wrinkled seeds = phenotype
–the genotype is not always seen in the
phenotype]
Mendel’s Experiments
• Mendel’s experimental design
– Protocol #1: monohybrid crosses
• symbolic representation
P: SS x ss
F1:
Ss gamete formation S or s
self pollination: S with S
s with s
S with s or s with S
F2: SS, ss, Ss, sS
Punnett
to the
rescue
Figure 10.4
P: (SS or ss)
p(S)=1
F1: (Ss)
x
p(s)=1
p(Ss) =1 x 1=1
p(S)=1/2, p(s)=1/2, so
F2:
p(SS) =1/2 x 1/2=1/4
p(ss) =1/2 x 1/2=1/4
p(Ss)=[1/2x1/2=1/4] x 2=1/2
F1: Ss
replication
S-S & s-s
anaphase I
S-S or s-s
anaphase II
S or S or s or
s
Punnett
explained
by
meiosis
Figure 10.5
Mendel’s Experiments
• Mendel’s experimental design
– Protocol #1: monohybrid crosses
• if you know the genotypes of the parental
generation you can predict the phenotypes
of the F1 & F2 generations
P:
Round x wrinkled
F 1:
1/2 Round, 1/2 wrinkled
F2: 3/4 Round, 1/4 wrinkled OR all wrinkled
Mendel’s Experiments
• Mendel’s experimental design
– Protocol #1: monohybrid crosses
• if you know the genotypes of the parental
generation you can predict the phenotypes
of the F1 & F2 generations
P:
Round (Rr) x wrinkled (rr)
F 1:
1/2 Round (Rr), 1/2 wrinkled (rr)
F2: 3/4 Round, 1/4 wrinkled OR all wrinkled
(RR,Rr,rR,rr)
(rr)
a
test cross
distinguishes
between a
homozygous
dominant
and a
heterozygous
parent
Figure 10.6
Mendel’s Experiments
• Mendel’s experimental design
– Protocol #2: dihybrid crosses
• P: crossed true breeding plants with
different traits for two characters
• F1: scored phenotypes & self-pollinated
• F2: scored phenotypes
Mendel’s Experiments
• Protocol #2: dihybrid crosses
– results
• F1: all shared the traits of one parent
• F2:
–traits of both parents occurred in 5/8 of
F2 at a 9:1 ratio
–non-parental pairs of traits appeared in
3/8 of F2 at a 1:1 ratio
combining
probabilities
of two
characters
Figure 10.7
or
four
different
gametes
by
meiosis
in
F1
dihybrid
progeny
Figure 10.8
Mendel’s Experiments
• Protocol #2: dihybrid crosses
– results
• F1: all shared traits of one parent
• F2:
–traits of both parents occurred in 5/8 of
F2 at a 9:1 ratio
–nonparental pairs of traits appeared in
3/8 of F2 at a 1:1 ratio
–phenotypic ratios: 9:3:3:1
Mendel’s Experiments
• Protocol #2: dihybrid crosses
– phenotypic ratios: 9:3:3:1
• predictable if alleles assort independently
–character A - 3:1 dominant:recessive
–character B - 3:1 dominant:recessive
–characters A & B »9 dominant A & dominant B
»3 dominant A & recessive B
»3 recessive A & dominant B
»1 recessive A & recessive B
Mendel’s Experiments
• Protocol #2: dihybrid crosses
– a dihybrid test cross (A_B_ x aabb)
• F1 all with dominant parent phenotype, or
• 1:1:1:1 phenotypes
Mendel without the experiments: pedigrees
• tracking inheritance patterns in human
populations
– uncontrolled experimentally
– small progenies
– unknown parental genotypes
• Mendelian principles can interpret phenotypic
inheritance patterns
a pedigree of
Huntington’s
disease
Figure 10.10
a pedigree of
albinism
Figure 10.11
some Mendelian luck
• Multiple alleles
– a single gene may have more than two
alleles and multiple phenotypes
One Character, Four Alleles, Five Phenotypes
Figure 10.12
incomplete
dominance:
intermediate
phenotypes
Figure 10.13
some Mendelian luck
• Incomplete Dominance
– alters creates new intermediate phenotypes
– reveals genotypes
• Co-dominance
– creates new dominant phenotypes
co-dominance produces additional phenotypes
Figure 10.14
some Mendelian luck
• genes may interact
– epistasis
• for mouse coat color
–BB or Bb => agouti, bb => black
–AA or Aa => colored, aa => white
• AaBb x AaBb => 9 agouti, 3 black, 4 white
– 9 AA or Aa with BB or Bb
– 3 AA or Aa with bb
– 3 aa with BB, Bb; 1 aa with bb = 4 white
white, black & agouti
Figure 10.15
some Mendelian luck
• genes may interact
– hybrid vigor (heterosis)
• hybrids are more vigorous than either
inbred parent
hybrid vigor in maize
Figure 10.16
some Mendelian luck
• genes may interact
– quantitative traits
• some traits are determined by many genes,
each of which may have many alleles
some Mendelian luck
• environment may alter phenotype
– some traits are altered by the environment of
the organism
• penetrance: proportion of a population
expressing the phenotype
• expressivity: degree of expression of the
phenotype
variation in heterozygotes
due to differences
in penetrance
& expressivity
variation in the population due
to differences in penetrance,
expressivity & genotype
Figure 10.17
Drosophila melanogaster
Figure 10.18
More Mendelian luck: gene linkage
• gene linkage was first demonstrated in
Drosophila melanogaster
– some genes do not assort independently
• F2 phenotype ratios are not 9:3:3:1
• F1 test cross ratios are not 1:1:1:1
–more parental combinations appear than
are expected
–fewer recombinant combinations appear
than are expected
Mendel’s luck: some genes are linked
Figure 10.18
2300
test
cross
progeny
hypothetical
reproduction
without
crossing over
at prophase I
of meiosis
crossing over can change allele combinations of
linked loci
Figure 10.19
recombination frequency depends on distance
Figure 10.20
391/2300=0.17
17 map units
More Mendelian luck: gene linkage
• if genes were completely linked, only parental
phenotypes would result
• if genes assort independently phenotypes arise
in 9:3:3:1 ratio in F2
• when genes are linked, recombinant
phenotypes are fewer than expected
• recombinant frequencies depend on distance
– distances can be estimated from
recombination rates (1% = 1 map unit)
chromosome mapping
Figure 10.21
YyMm x yymm
expected/1000
actual/1000
wt yell. min. y/m
250 250 250 250
323 178 177 322
Mendel’s luck: sex-linked genes
• Sex determination
– honey bees: diploid female, haploid male
– grasshopper: XX female, XO male
– mammals: XX female, XY male
• SRY gene determines maleness
– Drosophila: XX female, XY male
• ratio of X:autosomes determines sex
– birds, moths & butterflies: ZZ male, ZW
female
Mendel’s luck: sex-linked genes
• genes carried on X chromosome are absent
from the Y chromosome
• a recessive sex-linked allele is expressed in the
phenotype of a male
– females may be “carriers”
– males express the single allele
sex-linked genes
Figure 10.23
Mendel’s luck: sex-linked genes
• human sex-linked inheritance can be deduced
from pedigree analysis
inheritance of X-linked
gene
Figure 10.24
Mendel’s Principles
• Principle of segregation
– two alleles for a character are not altered by
time spent together in a diploid nucleus
• Principle of independent assortment
– segregation of alleles for one character does
not affect segregation of alleles for another
character
• unless both reside on the same
chromosome