Patterns of Inheritance

Heredity
Patterns of
z Passing on a physical characteristic
Inheritance to future generations
– Eye color, ear shape, diseases, feather color
z Mendelian
Genetics Some things you probably already know about heredity

vChildren resemble their parents.

vChildren are not identical to their
parents.

Some things you already know about genes

Genes
v Genes are carried on chromosomes.
z Discrete hereditary units that
determine physical traits v Most eukaryotes are diploid. (have 2
copies of each chromosome).
–Segments of DNA coding for protein
v Genes are sequences of DNA that code
z Genetics for proteins (or at least for RNA).
–The study of the transmission of v Mutations happen.
inheritable traits
v There is variation in populations.
v Sex makes new combinations of
variations.

Terminology Paired alleles

z Genetic locus: site on a

chromosome where a
gene is located A a
z Allele: variation of same B b
gene carried on
homologous pairs of
chromosomes z Homozygous (AA or aa): paired alleles on
homologous chromosomes are the same
z Heterozygous (Aa): paired alleles are different

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Patterns of Inheritance

Relationship between alleles Genotype: genes carried on

of the same gene chromosomes
z Genotype: genetic make-up
z Dominant: the allele that is – Designated by letters
expressed in a heterozygote – Dominant gene in upper case letters
(produces physical appearance) – Recessive gene in lower case letters
z Recessive: the allele that is AA = homozygous dominant
masked in a heterozygote Aa = heterozygous
aa = homozygous recessive

Phenotype vs. Genotype

z Phenotype:
physical
manifestation of
genotype
–Brown eyes or
blue eyes

Gregor Mendel was the first to Peas can be mated by

study genetics experimentally artificially transferring pollen
z Used pea plants as a Hermaphroditic
model system flowers
z Developed two major z Stamen: male
genetic principles parts
– Principle of – Pollen: carry
male gametes
Segregation
z Carpel: female
– Principle of parts
Independent
– Ovary: contains
Assortment female gametes
Gregor Mendel, 1822–1884

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Patterns of Inheritance

Artificial Mendel used monohybrid

fertilization crosses to study single traits
z Two plants that
are mated are
called a cross z Used pure breeding plants
z Resulting peas are –Plant is homozygous for all genes
seeds (embryos) z Mated two individuals that differ
that will mature by only one trait
into the next –E.g, purple flowers vs. white flowers
generation

Phenotype: flower color

Various pea phenotypes Parental generation

F1: first generation

offspring
(first filial)

F2: second
generation
Offspring
(second filial)

Genotype: PP and pp Recessive phenotype

Parental cross: reappeared in F2 generation
PP X pp

F1: all
heterozygous

F2: genotypic ratio

1 PP : 2 Pp : 1 pp

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Patterns of Inheritance

Average phenotypic ratio for

all traits studied: 3 to 1 Offspring will have a
phenotypic ratio
of 3 to 1 only if paired alleles
assort randomly

What happens to paired Fertilization is random

alleles during meiosis?
z AA genotype z Either A or a from one parent can
– Possible gametes made: only A be fertilized by A or a from other
z aa genotype parent
– Possible gametes made: only a
z Aa genotype z Can use a Punnett square to
– Possible gametes made: A or a predict possible genotypes of
z So if both flowers are Aa genotype offspring
– 50% of sperm in pollen are A; 50% are a
– 50% of ova in carpal are A; 50% are a

Punnett Square Punnett Square: Aa X Aa

zSo if both parents are Pp genotype
– 50% of sperm are P; 50% are p
– 50% of ova are P; 50% are p

At any given
locus, you have
an equal chance
of passing on Each allele has an equal chance of
mom’s allele or combining with either allele of other
dad’s allele. parent

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Patterns of Inheritance

Mendel’s Principle of Are all the traits inherited from

Segregation one parent passed on together to
subsequent generations as a set?
z Pairs of genes separate during Dihybrid cross: Tracking two
gamete formation characteristics at once
–Each gamete carries only one allele z Parental organisms differ in two
for each gene (haploid) characteristics
– For example,
z Pairs of genes reform when y Seed shape: round vs. wrinkled
gametes fuse during fertilization and
y Seed color: yellow vs. green

Hypothesis: Actual
Dependent results:
assortment all four
z Are traits of possible
one parent phenotypes
always appear in F2
inherited generation
together?
z NO! phenotypic
– Reject hypothesis ratio
9:3:3:1

Mendel’s Principle of Independent Assortment

Independent Assortment
z Each different trait segregates
independently during gamete
formation
–Seed shape and seed color are
inherited separately from each other

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Patterns of Inheritance

Understanding meiosis is key to Simple dominance

understanding genetics
z Meiosis produces haploid gametes z Heterozygote (Aa)
z Paired alleles segregate (separate) has the same
during meiosis phenotype as
z Knowing genotype of gamete allows homozygous
prediction of phenotype and genotype
dominant (AA)
of offspring

Punnett square to predict How can you determine the genotype

inheritance of an of an individual exhibiting the
autosomal dominant trait dominant phenotype?
Homozygous dominant or heterozygous?

z Test cross: Cross a dominant individual

with a recessive individual to determine
genotype of dominant parent
z Recessive allele will unmask a recessive
allele carried by a heterozygous parent

Test Cross Mendel’s questions

If AA X aa If Aa X aa vHow can a trait “skip” a

generation? (In other words,
All Aa Half Aa how can a trait be recessive?)
(dominant phenotype)
(All dominant
phenotype) Half aa
(recessive phenotype)

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Patterns of Inheritance

How can an allele be recessive? How can an allele be recessive?

v Why does white show up only
v Alleles at the same locus are when it’s homozygous?
expressed independently of each
other.

v An allele doesn’t know if its

homolog is dominant or recessive.

How can an allele be recessive? How can an allele be recessive?

v Why does white show up only v If there’s no functional pigment
when it’s homozygous? protein, flower will be white.
v Maybe white allele is a
loss-of-function mutation:
no pigment is created.
v Could code for non-functional
protein, or not code for a
protein at all.

Remember Inborn Errors of

How can an allele be recessive? Metabolism?
Example: phenylalanine metabolism
v If there’s no functional pigment
allele, flower will be white.
v If there’s a functional pigment
allele, cells will keep making
pigment protein until there’s
enough. Most Inborn Errors are autosomal recessive:
• Asz Defective
Instructions
long as at enzyme
for
least È phenylyketonuria
constructing
1one alleleeach
codes [PKU]
enzyme
correctly
v Dosage compensation: it doesn’t inz the
enough pathway is coded
functional
Defective enzyme enzymeby will
a different
be made.
5 È alcaptonuria
gene.
matter how many copies of an As
• Only usual, forenzyme
if both
z Defective each gene
alleles code
È you
for
albino have two
nonfunctionalalleles.
6
allele are present. enzyme will the pathway be interrupted.

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Patterns of Inheritance

Incomplete Dominance Incomplete

Dominance
Most loci do not
show complete
dominance.
“Gene dosage”
Cells with two copies
AA aa Aa of the dominant allele
z Alleles blend to produce intermediate make more gene
product than do cells
phenotype in heterozygotes with only one copy.

“Gene dosage”
Codominance

Two alleles (A or B) are both dominant over

a third allele (O), but not over each other

Polygenic Inheritance Chromosome Theory of Inheritance

¥
z Mendelian genes have specific loci on
Many phenotypes
AaBbCc AaBbCc

chromosomes
are the product of z Chromosomes undergo segregation
many genes 20⁄
aabbcc Aabbcc AaBbcc AaBbCc AABbCcAABBCcAABBCC
and independent assortment
interacting.
64

15⁄
Molecular probe for a
64
specific gene shows two
Fraction of progeny

distinct spots (one per

chromatid) on each of two
different chromosomes
6⁄ (homologous pair).
Inheritance of skin 64

color in humans
1⁄
Figure 14.12 64

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Patterns of Inheritance

Chromosome Theory of Inheritance Chromosome Theory of Inheritance

P Generation Yellow-round Green-wrinkled
seeds (YYRR) seeds (yyrr)

z The chromosomal Y
Y R R y
r
y

r z T.H. Morgan and the “Fly Room” ~ early 1900s

basis of Meiosis
z Fruit-fly, Drosophila melanogaster
Mendel’s laws
R Fertilization y r
Y
Gametes

All F 1 plants produce

yellow-round seeds (YyRr)
– Generation time = 2 weeks; fecundity = >100 offspring
F1 Generation R
r
y
R

r
y – N = 4 pairs of large chromosomes
Y

z Common allele in wild population: “wild type” (+).

Y
Meiosis
LAW OF
LAW OF INDEPENDENT
R r r R
SEGREGATION Metaphase I ASSORTMENT
z Spontaneous or experimentally induced variant:
Two equally
Y y probable Y y
arrangements
1 Alleles at both loci

“mutant”.
1 The R and r alleles of chromosomes
segregate
R r r R segregate White-eyed
Y y
Anaphase I
Y y
mutant: w allele
R r r R
z Genes typically
2 Each gamete Metaphase II
named for the
2 Each gamete
gets either the Y y gets one of
y y
R or r allele. four allele

Gametes
Y
R R
Y
r
Y
Y
r r
Y Y
r R
y
R
y
combinations
. mutant phenotype.
1 1 yr 1 1
YR yr yR
4 4 4 4
F2 Generation Red-eyed
Fertilization among the F 1 plants
3 Fertilization recombines 3 Fertilization results in the
9:3:3:1 phenotypic ratio in wild type: w+ allele
Figure 15.2
the R and r alleles at
9 :3 :3 :1 the F 2 generation. Figure 15.3
random.

Segregation, yes — Sex-linked inheritance

but not-so-independent assortment z Drosophila has XY sex determination
– XX are female P X
W+
X
X
W
z Monohybrid cross of w+w+ x w w Generation X Y
Figure 15.4
– XY are male W+
– 100% of F 1 red-eyed (w +w)
– Red-eyed allele must be
P
Generation
X z Thus, if eye-color gene Ova
(eggs)
W
Sperm
dominant is on the X chromosome, Generation
F
W 1 + W+ W+

y So far so good
F1
males are hemizygous W

z Next, F1 x F1
Generation (have only one version Ova W+
Sperm
F (eggs)
– F2 red-eyed & white eyed (3:1)
of that gene) and cannot Generation W 2
+ W+ W+

y As expected from Mendelian law of segregation ever be heterozygous W

W+
W W

z But, all white-eyed progeny are male!?! z The first solid evidence W+

– Inheritance of phenotype is dependent upon gender! indicating that a specific

– “sex-linked” F 2
gene is associated with
Generation
a specific chromosome

Genetic sex determination Genetic sex determination

I. Male-determining gene on Y chromosome I. Male-determining gene on Y
3+
XX
3+
XY chromosome Parents 44 +
XY
44 +
XX

(a) The X–Y system

II. Female-determining gene on W chromosome 22 +
X
Sperm 22 +
Y
Ova 22 +
X
76 + 76 +
ZW ZZ
44 + Zygotes 44 +
XX (offspring) XY
(c) The Z–W system

III. Dose-dependent female-determining gene on (a) The X-Y system in humans

Figure 15.9
X chromosome
22 + 22 + 16 16
XX X (Diploid) (Haploid) v X chromosome: 153 Mbp, 900-1200 genes
v Y chromosome: 23 Mbp, 78 genes
(b) The X–0 system (d) The haplo-diploid system
Figure 15.9

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Patterns of Inheritance

Sex-linked genes Inheritance of

sex-linked genes
z Genes carried on
sex chromosomes,
but not related to
sex determination

z X-linked traits are expressed in males with only 1 gene (XrY)

z Females must be homozygous recessive for phenotype (XrXr)

Recessive disorders
X inactivation in Female Mammals
on human X-linked genes z In mammalian females one of the two X chromosomes in each
z Colorblindness: lacking receptors in retina that cell is randomly inactivated during embryonic development
detect a particular color – So both males and females have only one functional X per cell
z Duchenne Muscular Dystrophy (DMD): z If a female is heterozygous for a particular gene located on the
progressive muscle degeneration X chromosome, she will be a mosaic for that character
z Hemophilia: lacking blood clotting factors Two cell populations
in adult cat:

Active X

Early heterozygous embryo: Orange

X chromosomes fur
Cell division
and X Inactive X
chromosome Inactive X
inactivation
Allele for Black
orange fur fur
Allele for
black fur Active X
“Tortoise-shell
Tortoise-shell”” mosaic coloration — only occurs in female cats Figure 15.11

Mendelian vs. chromosomal Linked genes

inheritance Morgan’s Fly Room continues …
z Independent assortment of chromosomes zDihybrid cross (b+b+ vg+vg+) x (bb vgvg)
explains independent assortment of genes on y Gray body (b+b+) x black body (bb)
separate chromosomes y Normal wings (vg+vg+) x vestigial wings (vg vg)
P Generation
(homozygous)
But … Wild type
(gray body,
x Double mutant
(black body,
vestigial wings)
normal wings)
z Each chromosomes has several hundred gene b+ b+ vg+ vg+
F1 dihybrid
b b vg vg

loci! (wild type)

(gray body,
normal wings)

z So, how do you get independent assortment of b+ b vg+ vg

–All F1 gray body/normal wings (b+b vg+vg)

genes occurring on the same chromosome?
y As expected from Mendelian prediction
z Sometimes you do, sometimes you don’t!
– “linked genes” Figure 15.5

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Pa#erns  of  Inheritance  

Linked genes Linked genes

• Dihybrid cross (b+b+ vg+vg+) x (b b vg vg) è (b+b vg+vg) ❚ Dihybrid  cross  (b+b+  vg+vg+)  x  (b  b  vg  vg)  è  (b+b  vg+vg)  
è all F1 gray body/normal wings è  all  F1  gray  body/normal  wings  

• Now, perform test cross of F1 ❚Now,  perform  test  cross  of  F1  
• (b+b vg+vg) x (b b vg vg) ❙ (b+b  vg+vg)  x  (b  b  vg  vg)  
P Generation Double mutant P Generation Double mutant
(homozygous) (black body, (homozygous) (black body,
Wild type
– dependent assortment prediction: Wild type
x vestigial wings) x vestigial wings)
Double mutant ❙ 50% gray body/normal wings (b+b vg+vg) Double mutant
– Mendelian prediction (gray body,
normal wings)
(black body,
(gray body,
normal wings)
(black body,
❙ 50% black body/vestigial wings (bb vgvg)
independent assortment: b+ b+ vg+ vg+
vestigial wings) b b vg vg
– independent assortment prediction: b+ b+ vg+ vg+
vestigial wings) b b vg vg
F1 dihybrid F1 dihybrid
❙ 25% gray body/normal wings (b+b vg+vg) (wild type)
Double mutant
TESTCROSS
Double mutant
❙ 25% gray body/normal wings (b+b vg+vg) (wild type)
Double mutant
TESTCROSS
(black body, Double mutant
❙ 25% gray body/vestigial wings (b+b vgvg) (black body, x (black body, x
(gray body, vestigial wings) ❙ 25% gray body/vestigial wings (b+b vg vg) (gray body, (black body,
vestigial wings) vestigial wings)
❙ 25% black body/normal wings (bb vg+vg) normal wings) normal wings) vestigial wings)
❙ 25% black body/normal wings (b b vg+vg)
b+ b vg+ vg b b vg vg b+ b vg+ vg b b vg vg
❙ 25% black body/vestigial wings (bb vgvg) meiosis meiosis
❙ 25% black body/vestigial wings (b b vg vg)
b vg
RESULTS b+vg
b+vg+ b vg b vg+
– Actual outcome (out of 2,300 progeny):
965 944 206 185
b+ vg+ b+b vg+vg 25% ❙ 42% gray body/normal wings (b+b vg+vg) Wild type Black- Gray- Black-
(gray-normal) vestigial vestigial normal
❙ 9% gray body/vestigial wings (b+b vg vg) b vg
b+ vg b+b vgvg 25% ❙ 8% black body/normal wings (b b vg+vg) Sperm

bb vg+vg
❙ 41% black body/vestigial wings (b b vg vg)
b vg+ 25% b+ b vg+ vg b b vg vg b+ b vg vgb b vg+ vg
– Conclusions:
b vg b+b vg+vg 25% ❙ Parental phenotypes preferentially inherited Parental-type
offspring
Recombinant (nonparental-type)
offspring

Figure 15.9 ❙ b and vg genes are linked — Usually inherited as a unit Figure 15.9

b+ vg+ Testcross parents b vg

Linked genes
Gray body, Black body,
vestigial wings

Recombination
normal wings
(F1 dihybrid) b vg × b vg
(double mutant)

Replication of Replication of

& segregation of
chromosomes chromosomes

Morgan determined that b+

vg
b
vg

• Genes that are close together on the same chromosome are linked and
linked loci b+ vg+ b
vg
do not assort independently b
vg
b
vg

• Unlinked genes are either on separate chromosomes or are far apart on Meiosis I: Crossing
over between b and vg
b vg b vg
the same chromosome and assort independently loci produces new allele
combinations.
• Crossing-over can cause loci on the same chromosome to be
segregated independently in meiosis • Recombination frequency Meiosis I and II:
Even if crossing over
occurs, no new allele
– The closer the loci are to each other, the less likely a crossing-over event = (# recombinations/total # progeny) x100 combinations are
will occur between them — “tightly linked” Meiosis II: Segregation
produced.

– The farther apart, the more likely they will be inherited independently So for b & vg loci of chromatids produces Recombinant
recombinant gametes chromosome
(391/2300)100 = 17% with the new allele
combinations. Gametes
= 17 “linkage units” apart Ova Sperm
b+vg+ b vg on chromosome II b+vg+ b vg b vg+
b+ vg
X
Parents b vg

in testcross b vg b vg

Testcross b+ vg+ b vg b+ vg b vg+ Ova

offspring
965 944 206 185
Sperm
b+ vg+ b vg Wild type Black- Gray- Black-
Most (gray-normal) vestigial vestigial normal
offspring or b+ vg+ b vg+ b+ vg+ b vg+
b vg

b vg b vg b vg b vg b vg b vg

Parental-type offspring Recombinant offspring Figure 15.10

Linkage map of a chromosome Linkage map of a chromosome

§ In humans, I cM ≈ I million bp
• The map of the relative position of loci on a § But since crossing-over is not purely random, there is
chromosome based upon recombination considerable intra-species and interspecies variation
frequencies between those loci § If linkage distance = 50 cM, then there is a 50:50 chance of
• Map units are expressed as centimorgans (cM) a crossover.
I
§ I centimorgan = 1% crossover frequency § So any loci ≥50 cM apart are segregated and inherited
IV
II
Y X
III
independently (as if on separate chromosomes)
Recombination
frequencies
9% 9.5% Drosophila chromosome II
17%
Mutant phenotypes
Short Black Cinnabar Vestigial Brown
aristae body eyes wings eyes
b cn vg Figure 15.11
Chromosome
0 48.5 57.5 67.0 104.5
FOR EXAMPLE: On Drosophila chromosome II there occurs crossovers 9% of the time
between the b locus and the cn locus during meiosis and gametogenesis; and there occur
crossovers 9.5% of the time between the cn locus and the vg locus.
Hence b and cn are 9 cM apart; and cn and vg are 9.5 cM apart.
Long aristae Gray Red Normal Red
NOTE: The distance between b and vg is underestimated by crossover frequency. The
(appendages body eyes wings eyes
farther apart two loci are, the more likely that a second crossover will negate the first one. on head)
Wild-type phenotypes Figure 15.12

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Patterns of Inheritance

Some inheritance patterns seem to Epistasis

follow neither Mendelian nor q The expression or non-
chromosomal models expression of the epistatic
gene suppresses the
expression of another gene
q Epistasis q E.g., …
ßFor the mouse coat-color
q Pleiotropy gene, black (B) is
dominant over brown (b).
q Genomic imprinting ßBut if the pigment-
q Extra-nuclear genes production gene is
homozygous recessive
q Environmentally-restricted (cc), no pigment is
produced and coat color
expression is white, no matter what
the genotype of the coat-
color gene is!
Figure 14.11

Pleiotropy Genomic imprinting

Normal Igf2 allele
q A gene with Paternal
pleiotropic z The “silencing” of
expression affects certain genes that
Maternal

multiple phenotypic are “stamped” with Mutant

Wild-type mouse
(normal size)
an imprint during lgf2 allele
characteristics.
gamete production
Mutant
q Some of these effects z The phenotypic lgf2 allele

may epistatically effects of certain Paternal

modify other gene genes depend on
expression which allele is Maternal Dwarf mouse
inherited from the Normal Igf2 allele
mother and which is with imprint Figure 15.17

Codominance: heterozygotes produce two kinds of hemoglobin

inherited from the When a normal Igf2 allele is inherited from the father,
heterozygous mice grow to normal size.
One in ten African-Americans carries the sickle-cell trait (heterozygous) father But when a mutant allele is inherited from the father,
One in four-hundred has sickle-cell disease (homozygous) heterozygous mice have the dwarf phenotype.

Extra-nuclear genes Environmentally-restricted expression

q Environmental determination of phenotype and gene expression
z Human mitochondrial DNA contains 37 genes
1. Temperature-dependent melanin production in bunnies
z Bryophyte chloroplast DNA contains 128 genes 2. Soil-pH-dependent pigmentation in hydrangea flowers
3. Photoperiod-dependent coloration in arctic foxes
z The inheritance of traits controlled
by genes present in the chloroplasts Figure 15.18
or mitochondria usually depends
solely on the maternal parent
because the zygote’s cytoplasm
comes from the egg

ß Yellow-blotch leaf phenotype inherited

directly from maternal lineage
ß Similarly, mitochondrial myopathy in
humans inherited from mother

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