Chapter 1Chapter 144

MendelMendelandand

TThe Gehe Gene Ideane Idea

Genetics developed from curiosity about Genetics developed from curiosity about inheritance.inheritance.

Early Ideas of Heredity

• Species maintained without significant change since time of creation (immutable)

• Traits are transmitted directly and independently. (Blended)

– Paradox - all members of same species should eventually have the same appearance

• Hybrids differ in appearance!

Early Ideas of Heredity

• Early geneticists demonstrated some forms of an inherited character can:– disappear in one generation and reappear,

unchanged, in future generations.– segregate among offspring of a cross.– be more likely to be represented than

alternative forms.

Josef Koelreuter - 1760

• Beginnings of modern genetics

• Crossed different strains of tobacco

• Traits masked in one generation to reappear in next.

• Contradicted theory of direct transmission

T. A. Knight - 1760

• Bred peas to further substantiate Koelreuter’s work.

• Like Koelreuter, failed to keep data of results!

Blending HypothesisBlending Hypothesis

Early 1800sEarly 1800s

Parental genetic material “blends” in Parental genetic material “blends” in offspring like mixing paint.offspring like mixing paint.

red-flowered parent + yellow flowered parentred-flowered parent + yellow flowered parent

+

ExceptionsExceptions

• Red-flowered parents produced yellow offspring

• Traits would disappear in one generation and reappear in a later one

Particulate Hypothesis of InheritanceParticulate Hypothesis of Inheritance

• Gregor Mendel (1856-1863)Gregor Mendel (1856-1863)

• Applied an experimental Applied an experimental (quantitative study) approach (quantitative study) approach to question of inheritanceto question of inheritance

• Separate and distinct factorsSeparate and distinct factors

• Factors retain identity Factors retain identity generation after generationgeneration after generation

Mendel’s Garden

Mendel’s Choice of PeasMendel’s Choice of Peas

• Short life cycleShort life cycle

• InexpensiveInexpensive

• Many varietiesMany varieties

• Many offspringMany offspring

• Distinctly contrasting phenotypesDistinctly contrasting phenotypes

• The expression of one trait did not The expression of one trait did not influence the expression of a second influence the expression of a second traittrait

What is a Mendelian Trait?What is a Mendelian Trait?

A mendelian trait is one that segregates in accordance with the laws of genetics set forth by Gregor Mendel. As such, it is controlled by a singlesingle gene locus.

• Identified “true-breeding” plants. (homozygous)• Crossed true-breeding plants that had distinct

and contrasting traits. (hybridization)• Permitted hybrid offspring to self-fertilize for

several generations.

Mendel’s Experimental DesignMendel’s Experimental Design

• Traits of offspring (FTraits of offspring (F11 generation) not generation) not

blended but resembled one of parents.blended but resembled one of parents.

• Expressed trait = dominantExpressed trait = dominant

• ““Hidden” trait = recessive.Hidden” trait = recessive.

• Recessive trait reappeared in FRecessive trait reappeared in F22

generation in a 3:1 (phenotypic) ratio but a generation in a 3:1 (phenotypic) ratio but a 1:2:1 (genotypic ratio)1:2:1 (genotypic ratio)

What Mendel FoundWhat Mendel Found

Mendel’s Four HypothesesMendel’s Four Hypotheses(Using modern terms)(Using modern terms)

1. There are alternative forms of genes called allelesalleles.

2. An organism has two alleles for the gene, one from each parent.

3. The allele that affects a trait is called the dominantdominant allele. The other allele that does not appear to affect the trait is called the recessiverecessive allele.

4. The two alleles for a character segregate (separate) during the formation of gametes (sex cells), so that each gamete carries only one allele for each character.

Mendel’s 1Mendel’s 1stst Law of Heredity Law of Heredity

Law of Segregation*Law of Segregation*

Two alleles for a trait segregate Two alleles for a trait segregate (separate) independently during the (separate) independently during the formation of gametes (sex cells).formation of gametes (sex cells).

Based on Mendel’s work with monohybrid crosses.

Mendel’s 2Mendel’s 2ndnd Law of Heredity Law of Heredity

Law of Independent Assortment*Law of Independent Assortment*

Genes located on different chromosomes Genes located on different chromosomes assort independently.assort independently.

Based on Mendel’s work with dihybrid crosses.

Inheritance follows laws of chance.

Monohybrid CrossesMonohybrid Crosses

Determine:Determine:

• Which characteristic is dominant?Which characteristic is dominant?

• Parental genotypesParental genotypes

• Possible gametes and genotypes of Possible gametes and genotypes of parentsparents

Monohybrid CrossMonohybrid Cross

PP pp

Results in F2 phenotypic ratio of 3:1

P

P

p p

Pp Pp

Pp Pp

All plants are purple (phenotype)

PP X pp

P

p

P p

PP Pp

Pp pp

Pp X Pp

Phenotypes

¾ (75%) are purple

¼ (25%) are white

3:1 ratio

Let’s practiceLet’s practice

Monohybrid Cross

Certain breeds of guinea pigs can have dark fur (D) or white fur (d). Assume that two such guinea pigs that are heterozygous (hybrid) for fur color are crossed. What do you predict will be the phenotypic and genotypic mix of the F1 generation?

D

d

D d

DD Dd

Dd dd

Dd X Dd

F1 Genotypes ¼ - DD¼ - dd½ - Dd

F1 Phenotypes ¾ - Dark fur¼ - White fur

Monohybrid Cross

Albinism is a condition that results when an animal does not have the pigment melanin. The gene for albinism is recessive (a). Cross an albino female rabbit with a normal rabbit, whose father was albino.

How do you determine the genotype of the “normal” rabbit?

What is it?

A

a

a a

Aa Aa

aa aa

F1 Genotypes ½ - Aa½ - aa

F1 Phenotypes ½ - Normal½ - Albino

Aa X aa

Monohybrid Cross

Humans have earlobes of two shapes: attached or free. Free earlobes are dominant (F) over attached (f) earlobes. Cross two parents that are heterozygous for free earlobes.

F

f

F f

FF Ff

Ff ff

F1 Genotypes ¼ - FF¼ - ff½ - Ff

F1 Phenotypes ¾ - Free earlobes¼ - Attached

Monohybrid Cross

Yvette has very light colored eyebrows (EhEh). Her mother and father both have medium eyebrows (EHEh). Eyebrow color is an example of incomplete dominance – neither trait is expressed over the other. What would be the possibility of Yvette having a sibling that has dark eyebrows (EHEH)?

EH

Eh

EH Eh

EHEH EHEh

EHEh EhEh

F1 Phenotypes ¼ - Dark¼ - Light½ - Medium

EHEH – Dark

EHEh – Medium

EhEh – Light

The probability of having a sibling with dark eyebrows is 1 in 4 (25%).

Mating of an individual of unknown genotype but dominant phenotype with a homozygous recessive individual.

Can determine whether an individual with the dominant phenotype is homozygous dominant or heterozygous for a particular trait.

Testcross (one-trait)Testcross (one-trait)

TestcrossTestcrossMating of an individual of unknown genotype but dominant phenotype with a homozygous recessive individual.

Dihybrid CrossDihybrid Cross

Mating of two organisms that differ in Mating of two organisms that differ in two characters.two characters.

Determining Gametes

AaBBCCDdee will yield 4 different gametes

ABCDe

aBCDe

ABCde

aBCde

Determining Number of Gametes

Number of gametes = 2n, where n= the number of heterozygote pairs in the cell.

AaBBCCDdee

22 = 4 possible gametes

Dihybrid CrossDihybrid Cross

Meaning of the 9:3:3:1 Ratio

9 – Exhibit both dominant phenotypes (R-Y-)

3 – Exhibit one of the recessive phenotypes and one of the dominant phenotypes. (rrY-)

3 – Exhibit the opposite recessive phenotype and the opposite dominant trait. (R-yy)

1 – Exhibit both recessive phenotypes, (rryy)

Punnett Square of Dihybrid Cross(RrYy RrYy)

Tree Diagram of Dihybrid Cross(SsYy SsYy)

Extending Mendelian Inheritance

• For Single Genes– Degrees of Dominance

• Incomplete dominance• Codominance

– Multiple alleles– Pleiotropic Effects

• For Two or More Genes– Epistasis– Polygenic Inheritance (Continuous Variation)

Incomplete Dominance

• Alleles neither fully dominant or fully recessive.

• Heterozygous phenotypes are “intermediate” between those of parents

Codominance (Multiple Alleles)

• Alleles neither fully dominant or fully recessive.

• Heterozygous phenotypes representative of both parents– ABO Blood Groups– Rh Blood Groups

Three alleles for human blood type. Any one person has only two. Combinations of these alleles result in six genotypes and four phenotypes. Alleles IA and IB are codominant. Allele i is recessive.

Codominance (Multiple Alleles)

Pleiotropic Effects

• One allele has more than one effect on a phenotype

• Multiple symptoms traceable to a single gene defect.– CF– sickle cell anemia

Epistasis

• One gene interferes with the expression of another. (Act sequentially)

• Results in modified Mendelian ratios• Animal coat color

9:7 Complementary Gene Action

15:1 - Duplicate Gene Action

Genotype Flower Color Enzyme Activities

9 C_P_Flowers colored;anthocyanin produced

Functional enzymes from both genes

3 C_pp

Flowers white;no anthocyanin produced

p enzyme non-functional

3 ccP_Flowers white;no anthocyanin produced

c enzyme non-functional

1 ccppFlowers white;no anthocyanin produced

c and p enzymes non-functional

9:7 Complementary Gene Action

13:3 – Dominant SuppressionCertain genes have the ability to suppress the expression of a gene

at a second locus.

12:3:1 – Dominant Epistasis

Polygenic Inheritance (Continuous Variation - Polygeny)

• Multiple genes act to influence a character

• Quantitative traits

• The more genes the more continuous

Examples of Polygenic InheritanceExamples of Polygenic Inheritance

• Skin color

• Height - of students in a large high school might range from about 125 cm to 200 cm, with students of every possible height in between.

Nature and Nurture

Environmental Impacton

Phenotype

Environmental Effects

• Tree leaves vary in size.• Temperature - Siamese

cats.• Nutrition – height.• Exercise – body shape• Exposure to sunlight – skin

pigmentation

Environment and Phenotype

• A phenotype for a character can depend on environment as well as genotype

• Norm of reaction - the phenotypic range of a genotype influenced by the environment

Norm of Reaction

Hydrangea flowers of the same genotype range from blue-violet to pink, depending on soil acidity

Impact of Environment on Phenotype

• Broadest for polygenic characters• Multifactorial - genotypes influenced by

many factors

Norms of Reaction

Take Home Lesson!Take Home Lesson!

The product of a genotype is generally not a single, rigidly defined phenotype but a range of possibilities influenced by environment.

Human Traits Follow Human Traits Follow Mendelian Inheritance Mendelian Inheritance

PatternsPatterns

Pedigrees

• Family trees that record and trace the occurrence of a trait in a family.

• Analysis of matings that have already occurred.

• Involves collection of family history.• Used because humans not convenient for

genetic research

Pedigree Symbols

Widow’s Peak Pedigree

Earlobe Attachment Pedigree

Sex-Linked Inherited DisordersSex-Linked Inherited Disorders

Color-BlindnessColor-Blindness HemophiliaHemophilia

Recessively Inherited DisordersRecessively Inherited Disorders

AlbinismAlbinism Cystic FibrosisCystic Fibrosis Tay-SachsTay-Sachs Sickle Cell Disease Sickle Cell Disease Phenylketonuria (PKU)Phenylketonuria (PKU)

Cystic FibrosisCystic Fibrosis

1 in 20 Caucasians are carriers.1 in 20 Caucasians are carriers.

1 in 2500 children1 in 2500 children

Failure of ClFailure of Cl¯ ions to pass through plasma ¯ ions to pass through plasma membranemembrane

~17-28 year life expectancey~17-28 year life expectancey

Gene therapy moderately successful.Gene therapy moderately successful.

Tay-Sachs DiseaseTay-Sachs Disease

1 in 3600 Jews of central and eastern European 1 in 3600 Jews of central and eastern European descentdescent

Slowed development, blind, seizures, paralysis.Slowed development, blind, seizures, paralysis.

Most die by age of 3-4Most die by age of 3-4

Lack of hexoaminidase (Hex A) results in buildup Lack of hexoaminidase (Hex A) results in buildup of fatty substance in brain.of fatty substance in brain.

Sickle-Cell Disease

• 1 in 400 African-Americans• Defective hemoglobin (single aa substitution)

– Homozygotes have sickle-cell. (Example of pleiotropy)

– Heterozygotes: sickle cell trait; appear normal, but are resistant to malaria.

Sickle Cell and Malaria

Sickle-Cell DiseaseSickle-Cell Disease

PhenylketonuriaPhenylketonuria

1 in 10,000 – 15,000 births in U.S.1 in 10,000 – 15,000 births in U.S. Missing enzyme for normal metabolism of Missing enzyme for normal metabolism of

phenylalanine.phenylalanine. Abnormal product (phenylpyruvate) Abnormal product (phenylpyruvate)

accumulates in urineaccumulates in urine

Dominantly Inherited DisordersDominantly Inherited Disorders

AchondroplasiaAchondroplasia Huntington’s DiseaseHuntington’s Disease NeurofibromatosisNeurofibromatosis

• Less common

• Recessive alleles perpetuated by heterozygotes

• Dominant alleles (lethal) not passes on

AchondrplasiaAchondrplasia

1 in 25,0001 in 25,000

Huntington’s DiseaseHuntington’s Disease

1 in 20,0001 in 20,000 Progressive degeneration of brain cellsProgressive degeneration of brain cells Typically appears in middle age (problem!)Typically appears in middle age (problem!) Gene located on chromosome 4Gene located on chromosome 4

– Many repeats of CAG tripletMany repeats of CAG triplet Normal 11-34Normal 11-34 Disease 42>120Disease 42>120

Autosomal DominantAutosomal Dominant

NeurofibromatosisNeurofibromatosis– 1 in 3,0001 in 3,000

Multifactorial DisordersMultifactorial Disorders

Heart diseaseHeart disease DiabetesDiabetes CancerCancer AlcoholismAlcoholism Certain Mental IllnessesCertain Mental Illnesses

Genetic Counseling

• Identifies parents at risk of producing children with genetic defects.

– couples with recessive alleles– mothers older than 35

• Based on Mendelian Genetics and Probability Rules

Genetic Testing

• Assesses the state of early embryos.– ultrasound– amniocentesis– chorionic villi sampling

• Genomic analysis– Couples with recessive alleles– Huntington’s– BRCA1 & BRCA2 gene identification

Genetic Counseling

• Counselors can look for three things in cell cultures in search of genetic disorders:

– aneuploidy or gross alterations– proper enzyme functioning– association with known genetic markers