BTY222

Mendelian Genetics II-III

Pedigree analysis
&
Extended Mendelian Genetics
 Recap on Mendelian Genetics
• Monohybrid crosses:

1) Revealed that units factors or ( genes ) exist in pairs.

2) Unit factors for a given phenotype are either dominant or recessive ( Test cross)
3) The paired unit factors separate randomly during egg and pollen formation.

• Dihybrid crosses:

4) Revealed the law of independent assortment: Unit factors sort independently

during egg and pollen formation.

Can this experimental approach be used to study inheritance in humans ?

 Pedigree analysis: A family tree indicating the
presence or absence of a certain trait

Cross test approach is not possible

Observation are made on family

pedigrees

Individual who brought attention to investigation

 Pedigree analysis: autosomal recessive trait
Albinism, Sickle cell anemia and Cystic Fibrosis •Both males and females can be
carriers, affected, or normal.

•Recessive traits may skip a

generation

•Appears equally in both sexes

CARRIER: individual that

carries genetic information
that determines a disease
or condition but does not
expresses it.
What is the genotype of I3 / I4 ?
What are the genotypes for II-3 and II-4 ?
Recessive trait
 Pedigree analysis: autosomal dominant trait

Huntington's disease and neurofibromatosis type 1

•Carriers are not possible: individuals are either normal or affected

•Affected children have at least one affected parent
•Appear equally in both sexes
 Autosomal dominant trait

A dominant trait such as widow's peak cannot skip a generation.

If not observed in the next generation, the parental individual was heterozygote and the
dominant allele was lost.

Source: http://bio1151.nicerweb.com/Locked/media/ch14/pedigree.html
 Sex determination
X-X= female
X-Y = male
male is the heterogametic sex
( two different sex chromosomes)

Z-Z= male
Z-W = female
female is the heterogametic sex

Lepidoptera All Birds

(butterflies)
 X-linkage
Inheritance patterns of genes/ loci found in the X chromosome

Genes present in the X chromosome present patterns of

inheritance that are quite different from those observed in
autosomal genes.

These genes present dominant and recessive alternatives.

 X-linkage
Traits which are located on the X-chromosome

Early work of Thomas Morgan on

eye color of Drosophila: reciprocal
crosses

w: recessive X-linked
white

w+: dominant X-linked

red
Inheritance pattern of white eye
trait is related to the sex of parent
w: X-linked recessive
w+: X-linked dominant
 X-linked recessive.
X-linked recessive: Affected females passes condition on to all sons
males are hemizygous,
females are “carriers”.

e.g. color blindness, Hemophila A, Hemophilia B, Duchenne

 X-linked recessive
Hemophilia is a group of diseases in which blood does not clot normally. Factors in
blood are involved in clotting. Hemophiliacs lacking the normal Factor VIII have
Hemophilia A, the most common form.

http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookhumgen.html#Sex-linked%20traits
 The people with the disease are colored
fully red. Carriers have normal vision, but
one X chromosome is mutant - call it “Xc”.
An “XcX” is therefore a carrier. Only
females can be carriers, since males with
an “Xc” are “XcY” and are always
colorblind.

If a female is affected, all her sons will be affected.

A son always gets his X chromosome from his mother (because he gets his other
chromosome, the Y, from his father)

The daughters of a female who has the disease will always

be carriers, since they get one of their X chromosomes from their mother and one
from their father.

If a male is affected, all of his daughters will be carriers.

A daughter always gets one of her X chromosomes from her father.

http://sparkleberrysprings.com/v-web/b2/?p=801
 X-linked dominant inheritance.
Hypophosphatemic ricketsm,
oral-facial-digital syndrome type I,
Fragile X syndrome.

1. Carriers are not possible

2. Both sexes can be affected

3. Males transmit to all daughters

(never to sons)

4. Females transmit to both sexes

The following pedigree was drawn after a certain condition
was detected in the family.
What is the most likely mode of inheritance of this trait?
Provide reasons for each of the following possibilities to
accept or reject them:

1. Sex-linked, dominant
2. Sex-linked, recessive
3. Mitochondrial inheritance
4. Autosomal dominant
5. Autosomal recessive
6. Y-chromosome
Which mode of inheritance can be ruled out ?

• Autosomal D
• Autosomal r
• X-linked D
• X-linked r
• Y-linked
• mtDNA
 Extension of Mendelian Genetics:
Gene interactions and phenotype
Since Mendel’s work was rediscovered in the early 1900s:

Researchers have studied the many ways genes

influence an individual’s phenotype: neo-Mendelian
genetics (neo from Greek for “new”)

Explanations of ratios that did not conform to the

expected Mendelian ratios
 Gene interactions:

However, in the following examples showing

deviations from Mendelian expectations,
the principles of independent assortment
and segregation still hold,
and F2 phenotypic ratios are expressed in
fractions of 16
Genetic variation
• Alternative forms of a gene are called alleles
• Mutation is the source of alleles
• wild-type allele : most frequent in nature
usually dominant
New phenotypes result from changes in functional activity
of gene product
• Eliminating enzyme function (loss of function, null allele)*
• Changing relative enzyme efficiency
• Changing overall enzyme function
• changing in extent of expression

* Different concept in molecular genetics/ PCR

 Symbols for alleles
Dominant/ recessive : upper case/ lower case
Ww, Rr, etc

Wild type allele: italics and superscript (+)

example : Drosophila normal body color is gray

lower case: variant is recessive
e+/e+ gray fly +/+
e+ : wild type gray e+/e gray fly +/e
e : mutant ebony e /e ebony e/e

example : Drosophila dominant wrinkled wing (Wr) mutation

upper case: variant is dominant
Wr/Wr wrinkled (homozygote mutant)
Wr / Wr+ wrinkled (heterozygote mutant)
Wr+/ Wr+ straight (Wild type)
Symbols for alleles

When no dominance exists

IA IB

Multiple alleles: R1, R2, R3… RN

 Gene interactions and phenotype
1. Incomplete
dominance

Heterozygotes
display a “blended”
phenotype
R1 = red allele
R2 = white allele

Red and white not dominant or recessive

Genotypic ratios = phenotypic ratios

1:2:1
 Gene interactions and phenotype
2. Co-dominance
Joint expression of both alleles
M N MN
(no intermediate phenotype)

M-N blood groups

Autosomal , chr4, genotype phenotype
LMLN MN
Glycoprotiens M and N on red
LMLM M
blood cells LN LN N
 3. Multiple alleles
A case when 3 alternative alleles of a gene exists.

Human ABO blood type

• A and B antigens present on
surface of blood cells
• A and B antigens controlled
by a gene on chr9

Genotype Antigen Phenotype

IAIA A A
IAI A A
IBIB B B
IBI B B
II neither 0

I = isoagglutinogen, antigen
 Abnormal phenotype in ABO group:
Bombay phenotype
• Discovered in a Group 0 woman with AB and B
parents, and AB, A and B children in Bombay

• Mutation in FUT1 (fucosyl transferase) , A and B

antigens cannot be added to the antigenic
carbohydrate.
FUT1 = homoz. recessive

Bombay women
Genetically her blood type is B
 The ABO
antigen
• Antigen A and B : Carbohydrate groups
• Derived from H-substance

Homozygous recessive mutation in FUT 1

prevents production of H-substance due to
lack of fucosyl transferase.
 4. Lethal alleles
Lethal dominant: only 1 allele determines disease

e.g.: Huntington disease, onset in adulthood (neural and

motor degeneration until death)
Onset of the disease is delayed in heterozygotes, but they
eventually die.

Lethal recessive: phenotypic ratios= 2:1

instead of 3:1 if
homozygote recessive
was not born

See cross with animation at http://www.ansci.cornell.edu/usdagen/lethal_alleles

This site contains explanations to Meiosis, Mitosis, Mendelian genetics, and other inheritance topics we will see in this course
 Lethal alleles
• Some mutations are
deleterious in homozygote
state: recessive lethal allele

•AY : mutant allele yellow

•A : wild type gray

AY is dominant over A
(agouti) but lethal in AYAY
state, dye before birth.

Mutation (del) produces gain of function Wild type mutant

to coat, but lethal for embryonic
development by partial del of Merc.
 Multiple Gene interactions

Phenotypes affected by more than one genes or gene product.

-Whenever two or more loci interact to create new phenotypes

-Whenever an allele at one locus masks the effects of alleles at one or more other loci
-Whenever an allele at one locus modifies the effects of alleles at one or more other loci

Heterogeneous traits:

e.g.: eye in Drosophila

deafness in human : ~ 50 genes
eye color
 1. Epistasis
Epistasis : expression of one gene modifies the
effect of expression of another gene.

Epistatic allele Hypostatic allele

Gene 1 Gene 2

Gene 1: can be epistatic either in recessive or dominant state

e.g. epistatic recessive: Bombay phenotype (ABO),

agouti - yellow phenotype in mice

e.g. dominant epistatic: summer squash fruit shape

Recessive Epistasis

F1: Heterozygotes for both genes

Epistasis in mice
• Coat colour in mice is determined by
2 separate genes

• agouti (AA), is dominant to

solid-colored black fur aa

• gene (C) is necessary for

pigment production

• Homozygous mutant cc mice

cant produce pigment = albino

• The C gene is epistatic to the A

gene
 Dominant epistasis
Summer squash Cucurbita pepo

Allele A: white fruit BB bb

Bb
a: color fruit

Expression of color is Color type is

masked by A determined by locus B
 Dominant epistasis

F1
AaBb
A epist over B

White
(colorless)

Yellow
Green
 2. Novel phenotypes
Summer squash Cucurbita pepo

AaBb

Disc x long = disc

AABB x aabb = AaBb

AaBb x AaBb
A- B- aabb sphere
A- bb
aa B-
 2. Novel phenotype of squash:
equal influence of both genes
 Fractions of 16 in phenotypic
proportions indicate the interaction
between 2 genes

x
x

x
 Complementation
Is this phenotype produced by
mutations in the same gene or in
different genes?

Experimental design:
Mutant Mutant
Edward Lewis, 1918-2004
from strain 1 x from strain 2
Nobel Laureate Phys Med 1995

F1 phenotypes:

if mutant ?
if normal ?
The complementation test:

“when two strains of an organism

with different homozygous
recessive mutations that produce
the same mutant phenotype
produce offspring with the wild-
type phenotype when crossed”

The test is used to determine

whether the mutations in two
strains are in different genes
 Pleiotropy
One mutant gene producing multiple phenotypes

Sickle cell anemia (crescent shape red blood cell)

A single mutated betaglobulin gene produces numerous consequences
throughout the body.

Albinism ( defect in melanin production):

Mutation in tyrosinase gene affects production of melanin for which some forms are associated with
rapid-eye movement and light sensitivity.
 Sex limited
Sex-limited genes cause the two sexes to show different traits or phenotypes,
despite having the same genotype.

- This term is restricted to autosomal genes

- phenotypic expression limited to one sex

Genotype Phenotype Phenotype

in Females in Males
hh hen-feathered cock-feathered
Hh hen-feathered hen-feathered
HH hen-feathered hen-feathered
 Sex influenced

•autosomal genes, with

phenotypic expression being different in both sexes,
depending on individual hormonal constitution

Genotype Phenotype Phenotype

in Females in Males
BB bald bald
Bb nonbald bald
bb nonbald nonbald

A dominant effect in one sex and a recessive effect in the other

 Important concepts

• Incomplete dominance
• Codominance
• Multiple alleles
• Lethal alleles (recessive / dominant)

• Epistasis
• Pleiotropy

• sex-linked
 Very informative sites

http://biology200.gsu.edu/houghton/4564%20%2712/lecture2.html

http://www.ansci.cornell.edu/usdagen/lethal_alleles
many topics in this site

http://www.ualberta.ca/~pletendr/tm-modules/genetics/70gen-inherit.html

http://bio1151.nicerweb.com/Locked/media/ch14/

Interactive pedigree problems and solutions

https://msu.edu/course/zol/344/Elsea/Pedigrees/