Introduction to Genetics

• GENETICS – branch of biology that deals with heredity and variation of organisms.

• Chromosomes carry the hereditary information (genes)• Arrangement of nucleotides in DNA• DNA RNA Proteins

What is a gene?

• A gene is a stretch of DNA whose sequence determines the structure and function of a specific functional molecule (usually a protein)

DNA

Protein

…GAATTCTAATCTCCCTCTCAACCCTACAGTCACCCATTTGGTATATTAAAGATGTGTTGTCTACTGTCTAGTATCC…

Computer program

Specific function

…function sf(){document.f.q.focus()}…

Working copymRNA

Genes are located in the cell nucleus on chromosomes

Karyotype

Mendel’s laws

Concept 14.1: Mendel used the scientific approach to identify two laws of inheritance

• Mendel discovered the basic principles of heredity by breeding garden peas in carefully planned experiments

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Figure 14.1

Figure 14.2

Parentalgeneration(P) Stamens

Carpel

First filialgenerationoffspring(F1)

TECHNIQUE

RESULTS

3

2

1

4

5

Figure 14.2a

Parentalgeneration(P)

Stamens

Carpel

TECHNIQUE

2

1

3

4

Figure 14.2b

First filialgenerationoffspring(F1)

RESULTS

5

• Mendel chose to track only those characters that occurred in two distinct alternative forms

• He also used varieties that were true-breeding (plants that produce offspring of the same variety when they self-pollinate)

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Mendel deduced the underlying principles of genetics from these patterns

1. Segregation2. Dominance3. Independent assortment

Mendel looked at seven traits or characteristics of pea plants

Work was largely ignored for34 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 PREDICTED• The concept of genes• That genes occur in pairs• That one gene of each pair is present in the gametes

Gene – a unit of heredity; a section of DNA sequence encoding a single protein

Genome – the entire set of genes in an organism

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.

• In a typical experiment, Mendel mated two contrasting, true-breeding varieties, a process called hybridization

• The true-breeding parents are the P generation• The hybrid offspring of the P generation are called the F1

generation• When F1 individuals self-pollinate, the F2 generation is

produced

What Mendel called a “heritable factor” is what we now call a gene

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)

Allele for purple flowers

Homologouspair ofchromosomes

Allele for white flowers

Locus for flower-color gene

Monohybrid cross

• Crossing two pea plants that differ in stem size, one tall one short

T = allele for Tallt = allele for dwarf

TT = homozygous tall plantt t = homozygous dwarf plant

T T t t

Monohybrid cross: a genetic cross involving a single pair of genes (one trait); parents differ by a single trait.P = Parental generation

F1 = First filial generation; offspring from a genetic cross

F2 = Second filial generation of a genetic cross

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= 1:2:1Phenotype:3 Tall1 dwarf Phenotypic ratio= 3:1

Genotypes:100% T t

Phenotypes:100% Tall plants

Test Cross

• A heterozygous with a homozygous

T t t t

T

t

t T t

t t

Genotypes:50% T t50 % t t

Phenotypes:50% Tall plants50% Dwarf plants

You can still use the shortcut!

When you have an individual with an unknown genotype, you do a test cross.Test cross: Cross with a homozygous recessive individual.

Test cross

• If you get all 100% purple flowers, then the unknown parent was PP…

P p P p

P p

P p

P P p

p

P p p p

P p

p p

P p p

p

•If you get 50% white, 50% purple flowers,then the unknown parent was Pp…

How can we tell the genotype of an individual with the dominant phenotype?

Such an individual could be either homozygous dominant or heterozygous

The answer is to carry out a testcross: breeding the mystery individual with a homozygous recessive individual

If any offspring display the recessive phenotype, the mystery parent must be heterozygous

Mendel’s Principles

• 1. Law of Dominance:When two contrasting characters are present in a single individual (hybrid) only one character is considered as dominant (i.e. expressed) and the other is considered as recessive (i.e. unexpressed). In Mendel’s experiment the tall plants which were obtained in F1 generation are the dominant ones and the dwarf ones are recessive

• 2. Law of Segregation:Whenever a pair of factors for a character is brought together in a hybrid , they segregate or separate during the formation of gametes

(Law of purity of gametes)

• The concept, now known as the LAW OF SEGREGATION, states

• that the two alleles for a heritable character separate (segregate) during gamete formation and end up in different gametes

• Thus, an egg or a sperm gets only one of the two alleles that are present in the somatic cells of an organism

• This segregation of alleles corresponds to the distribution of homologous chromosomes to different gametes in meiosis

SOLVING COMPLEX GENETICS PROBLEMS WITH THE RULES OF PROBABILITY

• We can apply the multiplication and addition rules to predict the outcome of crosses involving multiple characters

• A dihybrid or other multi character cross is equivalent to two or more independent monohybrid crosses occurring simultaneously

• In calculating the chances for various genotypes, each character is considered separately, and then the individual probabilities are multiplied

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• The addition rule states that the probability that any one of two or more exclusive events will occur is calculated by adding together their individual probabilities

• The rule of addition can be used to figure out the probability that an F2 plant from a monohybrid cross will be heterozygous rather than homozygous

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Figure 14.9

Segregation ofalleles into eggs

Segregation ofalleles into sperm

Sperm

Eggs

1/2

1/2

1/21/2

1/41/4

1/41/4

Rr Rr

R

RR

RR

R

r

r

rr r

r

Figure 14.UN01

Probability of YYRR

Probability of YyRR

1/4 (probability of YY)

1/2 (Yy)

1/4 (RR)

1/4 (RR)

1/16

1/8

Figure 14.UN02

Chance of at least two recessive traits

ppyyRr

ppYyrr

Ppyyrr

PPyyrr

ppyyrr

1/4 (probability of pp) 1/2 (yy) 1/2 (Rr)

1/4 1/2 1/2 1/2 1/2 1/2 1/4 1/2 1/2 1/4 1/2 1/2

1/16

1/16

2/16

1/16

1/16

6/16 or 3/8

The Spectrum of Dominance

• Complete dominance occurs when phenotypes of the heterozygote and dominant homozygote are identical

• In codominance, two dominant alleles affect the phenotype in separate, distinguishable ways

• In incomplete dominance, the phenotype of F1 hybrids is somewhere between the phenotypes of the two parental varieties

• A process where the dominant gene is incompletely dominant over the recessive gene and produces a phenotype which is intermediate to the parental type

• Carl Correns (1864-1933)- German Botanist• Mirabilis jalapa (4’O clock plant), Antirrrhinum sp.

Incomplete dominance

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

R R R r

R r

r r

R r R

r

Non-Mendelian inheritance: additive traits

Snapdragon red colour is additive

Dominant vs additive inheritance

0%

50%

100%

0 1 2

Number trait alleles inherited

Trai

t val

ue

DominantAdditive

• Enzyme acts on a particular substrate and brings out a

expression of a particular trait• The original allele produces normal; enzyme while the modified

allele may produce normal or less efficient enzyme or may not produce any enzyme

• If the changed allele produces anon functional enzyme or no enzyme then it will not be able to produce the phenotypic expression. During which, the phenotypic expression depends solely on the functioning of unmodified allele. Hence the unmodified allele responsible for the expression of original phenotype is called dominant allele while the modified allele which does not contribute in the expression of the phenotype is called recessive allele.

Gene expresses itself by producing a particulate protein or enzyme

• Genetics beyond Mendel other patterns of inheritance

– Co-dominance– Incomplete dominance

• Co-dominance – both alleles expressed equally – –Example ABO blood types– (ABO blood type is also an example

of multiple alleles)• IA – A antigen on blood cells• IB – B antigen on blood cells• Io – no antigen on blood cells• Antigen in this case is a type of sugar

molecule reacting to which the immune system may respond

Multiple Alleles• Most genes exist in populations in more than two allelic

forms• For example, the four phenotypes of the ABO blood

group in humans are determined by three alleles for the enzyme (I) that attaches A or B carbohydrates to red blood cells: IA, IB, and i.

• The enzyme encoded by the IA allele adds the A carbohydrate, whereas the enzyme encoded by the IB allele adds the B carbohydrate; the enzyme encoded by the i allele adds neither

Multiple Alleles More than 2 alleles affect the phenotype equally &

separately not blended phenotype human ABO blood groups 3 alleles

IA, IB, i IA & IB alleles are co-dominant i allele recessive to both

Example of multiple alleles: Human Blood Type

• Alleles:– IA=A allele– IB=B allele– i=O allele

Table 5.1

Blood group Symbol Genoypes

A IAIA

IAiHomozygousHeterozygous

B IBIB

IBiHomozygousHeterozygous

AB IAIB Codominant

O ii HomozygousRecessive

Multiple alleles in rabbits

Pleiotropy Most genes are pleiotropic

one gene affects more than one phenotypic characterMost genes have multiple phenotypic effects. The ability of a gene to affect an organism in many ways is called pleiotropy.

1 gene affects more than 1 trait (character)dwarfism (achondroplasia) gigantism (acromegaly)

For example, pleiotropic alleles are responsible for the multiple symptoms of certain hereditary diseases, such as cystic fibrosis and sickle-cell disease

Polygenetic Inheritance• Qualitative variation

usually indicates polygenic inheritance.

• This occurs when there is an additive effect from two or more genes.

• Pigmentation in humans is controlled by at least three (3) separately inherited genes.

Epistasis

• In epistasis, a gene at one locus alters the phenotypic expression of a gene at a second locus

• For example, in mice and many other mammals, coat color depends on two genes

• One gene determines the pigment color (with alleles B for black and b for brown)

• The other gene (with alleles C for pigment color and c for no pigment color ) determines whether the pigment will be deposited in the hair

• Epistatis does not allow the gene to express itself fully

• Dominance works at interallelic but intragenic level

• Epistasis works at intergenic level

• Epistasis refers to all non-allelic interactions including complementary and duplicate interactions

Sperm

BC bC Bc bc

BbCcBBCcBbCCBBCC

BbCC bbCC BbCc bbCc

BbccBBccBbCcBBCc

BbCc bbCc Bbcc bbcc

BC

bC

Bc

bc

BbCc BbCc

14

14

14

14

14

14

14

14

916

316

416

Epistasis in Labrador retrievers

• Dihybrid crosses are those where we consider the inheritance of two characteristics at the same time.

Strictly speaking, this law applies only to genes on different, nonhomologous chromosomes or those far apart on the same chromosome

Genes located near each other on the same chromosome tend to be inherited together

Mendel had observed that the seeds of his pea plants varied in several ways – among them, whether the peas were round or wrinkled and whether they were green or yellow.

He did monohybrid crosses on both characteristics, but then decided to look at how they were inherited together….

• There are four possible combinations of the two characteristics. Peas can be:

• 1) round and yellow

• 2) round and green

• 3) wrinkled and yellow

• 4) wrinkled and green

• From his monohybrid trials, Mendel had discovered that the allele for yellow colour was dominant to that for green.

• He had also found that the allele for round peas was dominant to the allele for wrinkled peas.

• Starting with individuals that were homozygous, either for both dominant characteristics or both recessive characteristics, he set off breeding again…

Phenotype Round, yellow Wrinkled, green

Genotype RRYY rryy

Gametes all RY all ry

F1 all RrYy

All of the F1 generation would be heterozygous for both characteristics, meaning that they would all be round and yellow. As with monohybrid crosses, he then crossed two of the F1 generation together…

X

Phenotype Round, yellow

Genotype RrYy

Gametes RY, Ry, rY, ry

F2 We really need a punnet square for this…

X Round, yellow

RrYy

RY, Ry, rY, ry

RY¼

Ry¼

rY¼

ry¼

RY¼

RRYY RRYy RrYY RrYy

Ry¼

RRYy RRyy RrYy Rryy

rY¼

RrYY RrYy rrYY rrYy

ry¼

RrYy Rryy rrYy rryy

F29 3 3 1: : :

Round

Yellow

Round

Green

Wrinkled

Yellow

Wrinkled

Green

This is the typical ratio expected in a dihybrid cross.

Principle of Independent Assortment

• Based on these results, Mendel postulated the 3. Principle of Independent Assortment:

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

Genes get shuffled – these many combinations are one of the advantages of sexual reproduction

Concept 14.4: Many human traits follow Mendelian patterns of inheritance

• Humans are not good subjects for genetic research – Generation time is too long– Parents produce relatively few offspring– Breeding experiments are unacceptable

• However, basic Mendelian genetics endures as the foundation of human genetics

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Pedigree Analysis

• A pedigree is a family tree that describes the interrelationships of parents and children across generations

• Inheritance patterns of particular traits can be traced and described using pedigrees

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Figure 14.15

Key

Male Female Affectedmale

Affected female

Mating Offspring

1stgeneration

2ndgeneration

3rdgeneration

1stgeneration

2ndgeneration

3rdgeneration

Is a widow’s peak a dominant orrecessive trait?

(a) Is an attached earlobe a dominantor recessive trait?

b)

Widow’speak

No widow’speak

Attachedearlobe

Freeearlobe

FForFfWW

orWw

Ww ww ww Ww

Ww Ww Wwww ww ww

ww

Ff Ff Ff

Ff Ff

ff

ffffffFF or Ff

ff

Figure 14.15a

Widow’speak

Figure 14.15b

No widow’speak

Figure 14.15c

Attachedearlobe

Figure 14.15d

Freeearlobe

• Pedigrees can also be used to make predictions about future offspring

• We can use the multiplication and addition rules to predict the probability of specific phenotypes

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Recessively Inherited Disorders

• Many genetic disorders are inherited in a recessive manner

• These range from relatively mild to life-threatening

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The Behavior of Recessive Alleles

• Recessively inherited disorders show up only in individuals homozygous for the allele

• Carriers are heterozygous individuals who carry the recessive allele but are phenotypically normal; most individuals with recessive disorders are born to carrier parents

• Albinism is a recessive condition characterized by a lack of pigmentation in skin and hair

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Figure 14.16

ParentsNormal

Aa

Sperm

Eggs

NormalAa

AANormal

AaNormal(carrier)

AaNormal(carrier)

aaAlbino

A

A

a

a

Figure 14.16a

• If a recessive allele that causes a disease is rare, then the chance of two carriers meeting and mating is low

• Consanguineous matings (i.e., matings between close relatives) increase the chance of mating between two carriers of the same rare allele

• Most societies and cultures have laws or taboos against marriages between close relatives

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