Mendelian Inheritance

PATTERNS OF INHERITANCE

Mendelian Genetics• Transmission genetics• a set of principles that describe how

genes are transmitted from parents to offspring

Gregor Johann Mendel• Austrian monk, born

in what is now Czech Republic in 1822• Studied theology

and was ordained priest Order St. Augustine.

In 1866 he published Experiments in Plant Hybridization, (Versuche

über Pflanzen-Hybriden) in which he established his three Principles

of Inheritance

Work was largely ignored for 34 years, until 1900, when 3

independent botanists rediscovered Mendel’s work.

Mendel was the first biologist to use Mathematics – to explain his

results quantitatively.

Mendel predictedThe concept of genes (which he

called as unit factor of inheritance)That genes occur in pairs

That one gene of each pair ispresent in the gametes

Mendel’s Principles

1. Principle of Dominance:

One allele masked another, one allele was dominant over the other in the F1 generation.

2. Principle of Segregation:

When gametes are formed, the pairs of hereditary factors (genes) become separated, so that each sex cell (egg/sperm) receives only one kind of gene.

3. Principle of Independent Assortment

• “Members of one gene pair segregate independently from other gene pairs during gamete formation”

Genetics terms you need to know:

• Gene is a unit of heredity; a

section of DNA sequence

encoding a single protein

Alleles – two genes that occupy the same position

on homologous chromosomes and

that cover the same trait (like

‘flavors’ of a trait).

Locus – a fixed location on a

strand of DNA where a gene or one of its alleles

is located.

• Homozygous – having identical genes (one from each parent) for a particular characteristic.

• Heterozygous – having two different genes for a particular characteristic.

Dominant – the allele of a gene that masks or suppresses the expression

of an alternate allele; the trait appears in the heterozygous

condition.

Recessive – an allele that is masked by a dominant allele; does not

appear in the heterozygous condition, only in homozygous.

• Genotype – the genetic makeup of an organisms

• Phenotype – the physical appearance of an organism (Genotype + environment)

Monohybrid cross• Parents differ by a single trait.• Crossing two pea plants that differ in stem

size, one tall one shortT = allele for Tallt = allele for dwarf

TT = homozygous tall plantt t = homozygous dwarf plant

Monohybrid cross for stem length:

T T t t (tall) (dwarf)

P = parentalstrue breeding,homozygous plants:

F1 generation is heterozygous:

T t (all tall plants)

Monohybrid cross: F2 generation• If you let the F1 generation self-fertilize, the next

monohybrid cross would be:T t T t (tall) (tall)

T T T t

T t

t t

T t

T

t

Genotypes:1 TT= Tall2 Tt = Tall1 tt = dwarf Genotypic ratio= 1:2:1

Phenotype:3 Tall1 dwarf Phenotypic ratio= 3:1

Another example: Flower color

For example, flower color:

P = purple (dominant)

p = white (recessive)

If you cross a homozygous Purple (PP) with a homozygous white (pp):

P P p p

P p ALL PURPLE (Pp)

Cross the F1 generation:

P p P p

P P P p

P p

p p

P

p

P pGenotypes:1 PP2 Pp1 pp

Phenotypes: 3 Purple 1 White

Dihybrid crosses• Mating that involve parents that

differ in two genes (two independent traits)

For example, flower color:P = purple (dominant)p = white (recessive)

and stem length:

T = tall t = short

Dihybrid cross: flower color and stem length

TT PP tt pp (tall, purple) (short, white)

Possible Gametes for parents

T P and t p

F1 Generation: All tall, purple flowers (Tt Pp)

TtPp TtPp TtPp TtPpTtPp TtPp TtPp TtPpTtPp TtPp TtPp TtPpTtPp TtPp TtPp TtPp

tp tp tp tp

TP

TP

TP

TP

Dihybrid cross F2

If F1 generation is allowed to self pollinate, Mendel observed 4 phenotypes:

Tt Pp Tt Pp (tall, purple) (tall, purple)

Possible gametes:TP Tp tP tp

Four phenotypes observedTall, purple (9); Tall, white (3); Short, purple (3); Short white (1)

TTPP TTPp TtPP TtPpTTPp TTpp TtPp TtppTtPP TtPp ttPP ttPpTtPp Ttpp ttPp ttpp

TP Tp tP tp

TP

Tp

tP

tp

Dihybrid cross

9 Tall purple

3 Tall white

3 Short purple

1 Short white

TTPP TTPp TtPP TtPpTTPp TTpp TtPp TtppTtPP TtPp ttPP ttPpTtPp Ttpp ttPp ttpp

TP Tp tP tp

TP

Tp

tP

tp

Phenotype Ratio = 9:3:3:1

Genotype ratios (9): Four Phenotypes:1 TTPP2 TTPp2 TtPP4 TtPp1 TTpp2 Ttpp1 ttPP2 ttPp1 ttpp

Dihybrid cross: 9 genotypes

Tall, purple (9)

Tall, white (3)

Short, purple (3)

Short, white (1)

NON-MENDELIAN INHERITANCE

BEYOND SIMPLE DOMINANCE

Incomplete Dominance• Effect in which one allele is not fully

dominant over another, so the heterozygous phenotype is between the two homozygous phenotypes.

Incomplete DominanceSnapdragon flowers come in

many colors.

If you cross a red snapdragon (RR) with a white snapdragon (rr)You get PINK flowers (Rr)!

R R

R r

r r

Incomplete Dominance

When F1 generation (all pink flowers) is self pollinated, the F2 generation is 1:2:1 red, pink, white

R R R r

R r

r r

R r R

r

What happens if you cross a pink with a white?

Incomplete dominance

A pink with a red?

Codominance• Both alleles are fully expressed in

heterozygotes, and neither is dominant or recessive.

Human ABO Blood Group

• The three alleles of the human blood (A,B and O). Where A and B are

codominant with each other when paired. The O allele is recessive when

paired with either A or B allele.

So, if your genotype is AA or AO your blood type is A. If your genotype is BB or BO, your blood type is B. If you are OO, your blood type is O. And if A and

B allele is paired, they exist as codominant therefore your blood type

is AB.

• The blood type of the baby is heterozygous A (AO); and the blood type of the father and

mother is homozygous B and heterozygous A respectively. Is the

baby the biological son of the couple?

Epistasis and PleiotropySome traits are affected by multiple

gene products, an effect, called polygenic inheritance or epistasis.

A gene that controls multiple traits is said to be pleiotropic.

For example, several gene products affect the coat color of a Labrador

retriever, which can be black, yellow or brown.

• One gene is involved in the synthesis of melanin. A dominant allele synthesizes black melanin,

while a recessive allele synthesizes brown melanin

A dominant allele from a different gene causes melanin deposition. A dominant allele of this gene causes

deposition of melanin in the fur, while the recessive allele reduces

melanin deposition.

AUTOSOMAL INHERITANCE PATTERNS

Autosomal Dominant Pattern

An allele is inherited in an autosomal dominant pattern if the

trait it specifies appears in heterozygous people. The trait

tends to appear in every generation.

EXAMPLE 1

• Marfan syndrome is an autosomal dominant disorder. If a homozygous affected female marries a heterozygous affected male, what is the probability that their child develops the disease?

Marfan SyndromeThe disease is an autosomal dominant

disorder, meaning that people who inherit only one copy of the Marfan FBN1 gene from either parent will

develop Marfan syndrome and be able to transmit it to their children

The syndrome is caused by the misfolding of the protein fibrillin-1.

Fibrillin-1 is coded by the gene FBN1. The most serious

complications are defects of the heart valves and aorta, which often

lead to early death. People with Marfan tend to be unusually tall,

with long limbs and long, thin fingers.

PROBLEM 1

• A normal female marries a man with achondroplasia, their first born child was normal. What is the possible genotype of the father?

Achondroplasia• The word achondroplasia literally

means "without cartilage formation”. However, in

achondroplasia the problem is not in forming cartilage but in

converting it to bone (a process called ossification), particularly in the long bones of the arms and

legs.

Mutations in the FGFR3 gene cause achondroplasia. The FGFR3 gene

provides instructions for making a protein that is involved in the

development and maintenance of bone and brain tissue.

Individuals who inherit two altered copies of this gene typically have a severe form of achondroplasia that causes extreme shortening of the bones and an underdeveloped rib cage. These individuals are usually stillborn or die shortly after birth

from respiratory failure.

PROBLEM 2

• A heterozygous male for progeria marries a female which is heterozygous for the disease as well. Given that they produce a son who is homozygous for the disease and marries a normal female. What is the probability that there child might develop the disease as well?

Hutchinson-Gilford Progeria

Hutchinson-Gilford progeria syndrome is a genetic condition

characterized by the dramatic, rapid appearance of aging beginning in

childhood. Affected children typically look normal at birth and in early infancy, but then grow more slowly than other children and do not gain weight at the expected

rate.

Mutations in the LMNA gene cause Hutchinson-Gilford progeria

syndrome.

The LMNA gene provides instructions for making a protein

called lamin A. This protein plays an important role in determining the

shape of the nucleus within cells. It is an essential scaffolding

(supporting) component of the nuclear envelope, which is the membrane that surrounds the

nucleus.

Mutations that cause Hutchinson-Gilford progeria syndrome result in

the production of an abnormal version of the lamin A protein. The altered protein makes the nuclear

envelope unstable and progressively damages the nucleus, making cells

more likely to die prematurely.

Autosomal Recessive Pattern

An allele is inherited in an autosomal recessive pattern if the

trait specifies appears only in homozygous people. The trait tends

to skip generations.

EXAMPLE 2

• A male who is a carrier for Tay-Sachs disease marries a normal female, what is the probability that there child is normal? Carrier? Affected?

Tay-Sachs Disease

Tay-Sachs disease is a rare inherited disorder that progressively destroys

nerve cells (neurons) in the brain and spinal cord.

As the disease progresses, children with Tay-Sachs disease experience seizures, vision and hearing loss,

intellectual disability, and paralysis. An eye abnormality called a cherry-

red spot, which can be identified with an eye examination, is

characteristic of this disorder.

X-LINKED INHERITANCE PATTERNS

EXAMPLE 3

• What is the probability that a man who is normal and marries a woman that is carrier for red-green colorblindness will have a baby that is affected with the disease?

Red-Green Color Blindness

• Red-green color blindness is a recessive, sex linked trait

(encoded on the X chromosome). This results in much more men to

suffer from it than women. It is usually inherited from a

grandfather to his grandson, with the mother in between acting as

the carrier of the disease.

PROBLEM

• What is the probability that a couple, affected male and normal female, will have a daughter that is a carrier of an X-linked hemophilia disorder?

Hemophilia A

Hemophilia A, also called factor VIII (FVIII) deficiency or classic

hemophilia, is a genetic disorder caused by missing or defective factor VIII, a clotting protein.

Factor VIII (FVIII) is an essential blood-clotting protein, also known as anti-hemophilic factor (AHF). In humans, factor VIII is encoded by the F8 gene. Defects in this gene

results in hemophilia A, a recessive X-linked coagulation disorder.

Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy, affecting around 1 in 3,600 boys, which

results in muscle degeneration and eventual death.

The disorder is caused by a mutation in the dystrophin gene, the largest

gene located on the human X chromosome, which codes for the protein dystrophin, an important

structural component within muscle tissue

QUIZ• About 70% of Americans perceive bitter taste from the

chemical phenylthiocarbamide (PTC). The ability to taste this chemical result from a dominant allele (T) and not

being able to taste PTC is the result of having two recessive alleles (t). Albinism is also a single locus trait with a normal pigment being dominant (A) and the lack of pigment being recessive (a). A normally pigmented woman who cannot

taste PTC has a father who is an albino taster. She marries a homozygous, normally pigmented man who is a taster but

who has a mother that does not taste PTC. What are possible the genotypes and phenotypes of the possible

children? What percentage will be albinos? What percentage of the children will be non-tasters of PTC?