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Course code: GEN 604

Lecture 2

Mendelian laws

This week

• Mendels’ laws

• Non-Mendelian inheritance

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Mendel’s Laws Basic concepts of probability

• 1st law = Allele segregation (addition rule)

• 2nd law = Independent assortment

(multiplication rule).

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1st Law: of Segregation

• Half the gametes (eggs/sperm) an individual produces have one copy of the gene and half have the other copy. (Gametes are haploid – just one copy of each gene.)

• An individual with Rr: half their gametes have R and the other half have r.

• An individual with RR: half their gametes have the “first” R and half have the “second” R. You can’t tell them apart, so they are all R

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Mendel’s 1st Law (cont.) Law of Segregation

• Individuals inherit one allele of each gene from each parent (one via the sperm, one via the egg).

• Example:

• If egg has genotype TR and sperm has genotype Tr, the offspring has genotype TTRr.

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1st law= The addition rule • Mating: Aa x Aa

• Offspring: ¼ AA+ ½ Aa+ ¼ aa

• A- =offspring either AA or Aa

Pr(A-)= Pr(AA)+ Pr(Aa)

Pr(A-)= ¼(AA)+ ½ (Aa)= ¾

The combined probability that either of 2 mutually exclusive events will occur is the sum of their individual probabilities.

(e.g. rolling a die) 6

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• Mating: Aa x Aa

• Offspring: ¼ AA+ ½ Aa+ ¼ aa

• A- =offspring either AA or Aa

=

Event

AA, Aa, aa Elementary outcomes

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Mendel’s 2nd Law = The multiplication

rule = Independent Assortment • Different genes are inherited independently.

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The combined probability that 2

independent events will occur

together = the product of their

individual probabilities.

(e.g. Get both 50p and 25p heads)

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Mendel’s experiments

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Pea (Pisum sativum) advantages for genetics

– Pea plants are available in many varieties with

distinct characters with traits.

– Mendel had strict control over which plants mated

with which.

– Each pea plant has male (stamens) & female

(carpal/ pistil) sexual organs.

– In nature, pea plants typically self-fertilize.

– Mendel moved pollen from one plant to another to

cross-pollinate plants.

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The 7 traits, easily recognized, studied by Mendel

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Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

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Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

F1 Generation

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Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

F2 Generation

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Exceptions to simple inheritance: Non-Mendelian inheritance

Exceptions to Mendel’s Laws • These laws are true for the genes Mendel observed, but

exceptions to these laws in more experiments lead to many discoveries, including:

• Genes come in chromosomes. The law of independent assortment is only for genes on different chromosomes.

• Sex chromosomes pair XX (female mammals), XY (male mammals), breaking the 2 of each gene rule.

• Some genes have more than 2 alleles.

• Some traits are determined by combinations of multiple genes .

• Dominant / recessive rules can be more complex.

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Exceptions to Mendel’s Laws in details

1. Polygenic Traits: traits determined by the combined

effect of more than one pair of genes.

2. Intermediate Expression: blending can occur in the

phenotype when there is incomplete dominance resulting

in an intermediate expression of a trait in heterozygous

individuals.

3. Multiple-allele Series.

4. Modifying and Regulator Genes.

5. Incomplete Penetrance.

6. Sex related genetic effects.

7. Pleiotropy

8. Stuttering Alleles

9. Environmental Influences 19

A. Polygenic traits

•e.g.

1. Human stature: an additive effect

determined by numerous genes

•The combined size of all of the body parts

from head to foot determines the height of

an individual.

2. Human skin, hair & eye colour.

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B. Intermediate expression 1. In primroses red or white flowers are homozygous while

pink ones are heterozygous.

•The pink flowers result because the single "red" allele is

unable to code for the production of enough red pigment

to make the petals dark red.

2. The pitch of human male voices The lowest and highest

pitches apparently are found in men who are homozygous

(AA and aa), while the intermediate range baritones are

heterozygous (Aa).

3. The child-killer disease Tay-Sachs is characterized by

incomplete dominance. Heterozygous individuals are

genetically programmed to produce only 40-60% of the

normal amount of an enzyme that prevents the disease. 21

Primroses

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C. Multiple-allele series

• The ABO blood type system is controlled by a

multiple-allele series (3 alleles: A, B & O), but each

individual only inherits 2 of them (one from each

parent).

• Some traits are controlled by far more alleles: human

HLA system which is responsible for identifying and

rejecting foreign tissue in our bodies, can have at

least 30,000,000 different genotypes.

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Di. Modifying genes

•Alter how certain other genes are expressed in the

phenotype.

E.g.

A dominant cataract gene will produce varying degrees

of vision impairment depending on the presence of a

specific allele for a companion modifying gene.

However, cataracts also can be promoted by diabetes

and common environmental factors such as excessive

ultraviolet radiation and alcoholism.

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dII. Regulator genes

• Can either initiate or block the expression of other

genes.

• e.g.

• Production of specific proteins time control

• Control maturation and aging processes.

• Hox genes

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e. Incomplete Penetrance

• May be partially due to environmental factors and the influence of other genes, but other forces such as gene expression are likely at work as well.

• E.g. you may inherit the genes that are responsible for type 2

diabetes but never get the disease unless you become greatly

overweight, persistently stressed psychologically, or do not get

enough sleep on a regular basis.

• The genes that cause the chronic autoimmune disease, multiple

sclerosis , may be triggered by the Epstein-Barr virus and

possibly other specific environmental stresses.

Penetrance is said to be reduced or incomplete when some individuals fail to express the trait, even though they carry the allele.

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f. Sex Related Genetic effects

•3 categories of genes that may have

different effects depending on an individual's

gender: referred to as:

1. sex-limited genes

2. sex-controlled genes

3. genome imprinting

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f1. Sex-limited genes • Inherited by both men and women but

are normally only expressed in the

phenotype of one of them.

• E.g. the heavy male beard, while women have very fine and sparse facial hair.

Human gender differences in facial hair 28

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f2. Sex-controlled genes

• Are expressed in both sexes but

differently.

• E.g. gout is a disease that causes

painfully inflamed joints. If the gene is

present, men are nearly 8 times more

likely than women to have severe symptoms.

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f3. Genome/or genetic imprinting

• Genomic imprinting involves the physical marking

of a segment of DNA, discovered in the housefly

Sciara coprophilia

• Mark is retained and recognized throughout the life of the

organism inheriting the marked DNA

• Offspring expresses one allele, not both “Monoallelic

expression”

• Diabetes , psoriasis & some rare genetically inherited

diseases (e.g. a form of mental retardation known as

Angelman syndrome) can follow this inheritance pattern.

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e.g. genomic imprinting

– The Igf-2 gene encodes an insulin-like growth factor

• Functional allele required for normal size

• Igf-2m allele encodes a non-functional protein

– Imprinting results in the expression of the paternal allele

only

• Paternal allele is

transcribed

• Maternal allele is

transcriptionally silent

– Igf-2m Igf-2m ♀ x Igf-2 Igf-2 ♂

• Normal offspring

– Igf-2m Igf-2m ♂ x Igf-2 Igf-2 ♀

• Dwarf offspring

– Different results in reciprocal crosses generally indicate sex-linked traits

• In this case, it indicates genomic imprinting of autosomal alleles 31

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g. Pleiotropy

e.g.

• 1. A classic example of pleiotropy is the human disease

phenylketonuria (PKU).

• PKU can cause mental retardation and reduced hair and skin

pigmentation,

• PKUcan be caused by any of a large number of mutations in

a single gene that codes for the enzyme phenylalanine

hydroxylase, which converts the AA phenylalanine to

tyrosine

• 2. Albinism: the gene for this trait results in a deficiency of

skin, hair, and eye pigmentation + defects in vision.

• Pleiotropy = A single gene may be responsible for a variety of traits. 33

h. Stuttering Alleles • Some genetically inherited diseases have more severe

symptoms each succeeding generation due to

segments of the defective genes being doubled in their

transmission to children= referred to as stuttering

alleles or unstable alleles.

• E.g.

1. Huntington's disease,

2. 2. fragile-X syndrome,

3. 3. the myotonic form of muscular dystrophy .

• Mendel believed that all units of inheritance are passed

on to offspring unchanged. Unstable alleles are an important exception to this rule.

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i. Environmental Influences

• Uterus environmental characteristics in which

a fertilized egg is implanted & the health of the

mother can have major impacts on the

phenotype of the future child.

• e.g. oxygen deprivation or inappropriate

hormone levels, accidents, poor nutrition &

other environmental influences throughout life

can alter an individual's phenotype.

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Environmental impact on phenotype

Biston betularia

Morpha carbonaria, the

melanic Peppered Moth. The

proportions of this form vary in

different locations

• B. betularia morpha typica, the

standard light-coloured peppered

moth

Balancing selection: multiple alleles are actively maintained in the gene pool of a

population at frequencies above that of gene mutation (heterozygotes favoured)