Chapter 14 Mendel and the Gene Idea

Genetic Theories

1. Blending Theory - traits were like paints and mixed evenly from both parents.

2. Incubation Theory - only one parent controlled the traits of the children.

Ex: Spermists and Ovists 3. Particulate Model - parents pass on traits

as discrete units that retain their identities

in the offspring.

Gregor Mendel

• Father of Modern Genetics.

• Mendel’s paper was published in 1866, but was not recognized by Science until the early 1900’s.

Reasons for Mendel's Success

• Used an experimental approach.

• Applied mathematics to the study of natural phenomena.

• Kept good records.

• Mendel was a pea picker!

• He used peas as his study organism.

Why Use Peas?

• Short life span.

• Bisexual.

• Many traits known.

• Cross- and self-pollinating.

• (You can eat the failures).

Cross-pollination

• Two parents.

• Results in hybrid offspring where the offspring may be different than the parents.

Self-pollination

• One flower as both parents.

• Natural event in peas.

• Results in pure-bred offspring where the offspring are identical to the parents.

Mendel's Work

• Used seven characters, each with two expressions or traits.

• Example:

– Character - height

– Traits - tall or short.

Monohybrid or Mendelian Crosses

• Crosses that work with a single character at a time.

Example - Tall X short

P Generation

• The Parental generation or the first two individuals used in a cross.

Example - Tall X short

• Mendel used reciprocal crosses, where the parents alternated for the trait.

Offspring

• F1 - first filial generation.

• F2 - second filial generation, bred by crossing two F1 plants together or allowing a F1 to self-pollinate.

Results - Summary

• In all crosses, the F1 generation showed only one of the traits regardless of which was male or female.

• The other trait reappeared in the F2 at ~25% (3:1 ratio).

Mendel's Hypothesis

1. Genes can have alternate versions called alleles.

2. Each offspring inherits two alleles, one from each parent.

Mendel's Hypothesis

3. If the two alleles differ, the dominant allele is expressed. The recessive allele remains hidden unless the dominant allele is absent.

Comment - do not use the term “strongest” to describe the dominant allele.

Mendel's Hypothesis

4. The two alleles for each trait separate during gamete formation. This now called: Mendel's Law of Segregation

When does this occur?

Law of Segregation

Mendel’s Experiments

• Showed that the Particulate Model best fit the results.

Vocabulary

• Phenotype - the physical appearance of the organism.

• Genotype - the genetic makeup of the organism, usually shown in a code. – T = tall

– t = short

Helpful Vocabulary

• Homozygous - When the two alleles are the same (TT/tt).

• Heterozygous- When the two alleles are different (Tt).

6 Mendelian Crosses are Possible

Cross Genotype Phenotype

TT X tt all Tt all Dom

Tt X Tt 1TT:2Tt:1tt 3 Dom: 1 Res

TT X TT all TT all Dom

tt X tt all tt all Res

TT X Tt 1TT:1Tt all Dom

Tt X tt 1Tt:1tt 1 Dom: 1 Res

Test Cross

• Cross of a suspected heterozygote with a homozygous recessive.

– Ex: T_ X tt

If TT - all dominant

If Tt - 1 Dominant: 1 Recessive

Dihybrid Cross

• Cross with two genetic traits.

• Need 4 letters to code for the cross.

– Ex: TtRr

• Each Gamete - Must get 1 letter for each trait.

– Ex. TR, Tr, etc.

Number of Kinds of Gametes

• Critical to calculating the results of higher level crosses.

• Look for the number of heterozygous traits.

Equation

The formula 2n can be used, where “n” = the number of heterozygous traits.

Ex: TtRr, n=2

22 or 4 different kinds of gametes are possible.

TR, tR, Tr, tr

Dihybrid Cross

TtRr X TtRr

Each parent can produce 4 types of gametes.

TR, Tr, tR, tr

Cross is a 4 X 4 with 16 possible offspring.

Results

• 9 Tall, Red flowered

• 3 Tall, white flowered

• 3 short, Red flowered

• 1 short, white flowered

Or: 9:3:3:1

Law of Independent Assortment

• The inheritance of 1st genetic trait is NOT dependent on the inheritance of the 2nd trait.

• Inheritance of height is independent of the inheritance of flower color.

Comment

• Ratio of Tall to short is 3:1

• Ratio of Red to white is 3:1

• The cross is really a product of the ratio of each trait multiplied together. (3:1) X (3:1)

Probability

• Genetics is a specific application of the rules of probability.

• Probability - the chance that an event will occur out of the total number of possible events.

Genetic Ratios

• The monohybrid “ratios” are actually the “probabilities” of the results of random fertilization.

Ex: 3:1

75% chance of the dominant 25% chance of the recessive

Rule of Multiplication or Product Rule

• The probability that two alleles will come together at fertilization, is equal to the product of their separate probabilities.

Example: TtRr X TtRr

• The probability of getting a tall offspring is ¾.

• The probability of getting a red offspring is ¾.

• The probability of getting a tall red offspring is ¾ x ¾ = 9/16

Comment

• Use the Product Rule to calculate the results of complex crosses rather than work out the Punnett Squares.

Rule of Addition

• Rule of Addition—the probability of an event that can occur in two or more different ways

– Yy x Yy

• What is the chance of a heterozygous offspring?

–¼ + ¼ = 1/2

PpYyRr x Ppyyrr (trihybrid cross)

• What is the chance that an offspring will have at least 2 recessive traits? – ppyyRr =

• ¼ x ½ x ½ = 1/16 (Rule of Multiplication) – ppYyrr =

• ¼ x ½ x ½ = 1/16 – Ppyyrr =

• ½ x ½ x ½ = 2/16 – PPyyrr =

• ¼ x ½ x ½ = 1/16 – ppyyrr =

• ¼ x ½ x ½ = 1/16 Total = 6/16 = 3/8 (Rule of Addition)

Variations on Mendel

1. Incomplete Dominance

2. Codominance

3. Multiple Alleles

4. Epistasis

5. Polygenic Inheritance

Incomplete Dominance

• When the F1 hybrids show a phenotype somewhere between the phenotypes of the two parents.

• Often a “dose” effect

Ex. Red X White snapdragons

F1 = all pink

F2 = 1 red: 2 pink: 1 white

Result

• No hidden Recessive.

• 3 phenotypes and 3 genotypes (Hint! – often a “dose” effect)

– Red = CR CR

– Pink = CRCW

– White = CWCW

Another example

Codominance

• Both alleles are expressed equally in the phenotype.

• Ex. MN blood group

– MM

– MN

– NN

Result

• No hidden Recessive.

• 3 phenotypes and 3 genotypes (but not a “dose” effect)

Multiple Alleles

• When there are more than 2 alleles for a trait.

• Ex. ABO blood group

– IA - A type antigen

– IB - B type antigen

– i - no antigen

Result

• Multiple genotypes and phenotypes.

• Very common event in many traits.

Alleles and Blood Types

Type Genotypes

A IA IA or IAi B IB IB or IBi

AB IAIB

O ii

Comment

• Rh blood factor is a separate factor from the ABO blood group.

• Rh+ = dominant

• Rh- = recessive

• A+ blood = dihybrid trait

Epistasis

• When 1 gene locus alters the expression of a second locus.

• Ex: – 1st gene: C = color, c = albino

– 2nd gene: B = Brown, b = black

Gerbils

In Gerbils

CcBb X CcBb

Brown X Brown

F1 = 9 brown (C_B_)

3 black (C_bb)

4 albino (cc__)

Result

• Ratios often altered from the expected.

• One trait may act as a recessive because it is “hidden” by the second trait.

Epistasis in Mice

Problem

• Wife is type A

• Husband is type AB

• Child is type O

Question - Is this possible?

Comment - Wife’s boss is type O

Bombay Effect

• Epistatic Gene on ABO group.

• Alters the expected ABO outcome.

• H = dominant, normal ABO

• h = recessive, no A,B, reads as type O blood.

Genotypes

• Wife: type A (IA IA , Hh)

• Husband: type AB (IAIB, Hh)

• Child: type O (IA IA , hh)

Therefore, the child is the offspring of the wife and her husband (and not the boss).

Bombay - Detection

• When ABO blood type inheritance patterns are altered from expected.

Polygenic Inheritance

• Factors that are expressed as continuous variation.

• Lack clear boundaries between the phenotype classes.

• Ex: skin color, height

Genetic Basis

• Several genes govern the inheritance of the trait.

• Ex: Skin color is likely controlled by at least 4 genes. Each dominant gives a darker skin.

Result

• Mendelian ratios fail.

• Traits tend to "run" in families.

• Offspring often intermediate between the parental types.

• Trait shows a “bell-curve” or continuous variation.

Genetic Studies in Humans

• Often done by Pedigree charts.

• Why?

– Can’t do controlled breeding studies in humans.

– Small number of offspring.

– Long life span.

Pedigree Chart Symbols

Male

Female

Person with trait

Sample Pedigree

Dominant Trait Recessive Trait

Human Recessive Disorders

• Several thousand known:

– Albinism

– Sickle Cell Anemia

– Tay-Sachs Disease

– Cystic Fibrosis

– PKU

Sickle-cell Disease

• Most common inherited disease among African-Americans.

• Single amino acid substitution results in malformed hemoglobin.

• Reduced O2 carrying capacity.

• Codominant inheritance.

Tay-Sachs

• Eastern European Jews.

• Brain cells unable to metabolize type of lipid, accumulation of causes brain damage.

• Death in infancy or early childhood.

Cystic Fibrosis

• Most common lethal genetic disease in the U.S.

• Most frequent in Caucasian populations (1/20 a carrier).

• Produces defective chloride channels in membranes.

Recessive Pattern Diseases

• Usually rare.

• Skips generations.

• Occurrence increases with consaguineous matings.

• Often an enzyme defect.

Human Dominant Disorders

• Less common then recessives.

• Ex:

– Huntington’s disease

– Achondroplasia

– Familial Hypercholsterolemia

Inheritance Pattern

• Each affected individual had one affected parent.

• Doesn’t skip generations.

• Homozygous cases show worse phenotype symptoms.

• May have post-maturity onset of symptoms.

Genetic Screening

• Risk assessment for an individual inheriting a trait.

• Uses probability to calculate the risk.

General Formula

R = F X M X D

R = risk

F = probability that the female carries the gene.

M = probability that the male carries the gene.

D = Disease risk under best conditions.

Example

• Wife has an albino parent.

• Husband has no albinism in his pedigree.

• Risk for an albino child?

Risk Calculation

• Wife = probability is 1.0 that she has the allele.

• Husband = with no family record, probability is near 0.

• Disease = this is a recessive trait, so risk is Aa X Aa = .25

• R = 1 X 0 X .25

• R = 0

Risk Calculation

• Assume husband is a carrier, then the risk is:

R = 1 X 1 X .25

R = .25

There is a .25 chance that any child will be albino.

Common Mistake

• If risk is .25, then as long as we don’t have 4 kids, we won’t get any with the trait.

• Risk is .25 for each child. It is not dependent on what happens to other children.

Carrier Recognition

• Fetal Testing

– Amniocentesis

– Chorionic villi sampling

• Newborn Screening

Fetal Testing

• Biochemical Tests

• Chromosome Analysis

Amniocentesis

• Administered between 11 - 14 weeks.

• Extract amnionic fluid = cells and fluid.

• Biochemical tests and karyotype.

• Requires culture time for cells.

Chorionic Villi Sampling

• Administered between 8 - 10 weeks.

• Extract tissue from chorion (placenta).

• Slightly greater risk but no culture time required.

Newborn Screening

• Blood tests for recessive conditions that can have the phenotypes treated to avoid damage. Genotypes are NOT changed.

• Ex. Phenylketonuria (PKU)

Newborn Screening

• Required by law in all states.

• Tests 1 - 6 conditions.

• Required of “home” births too.

Multifactorial Diseases

• Where Genetic and Environment Factors interact to cause the Disease.

• Becoming more widely recognized in medicine.

Ex. Heart Disease

• Genetic

• Diet

• Exercise

• Bacterial Infection

Genes & Environment

Summary

• Know the Mendelian crosses and their patterns.

• Be able to work genetic problems (practice!).

• Watch genetic vocabulary.

• Be able to read pedigree charts.

• Be able to recognize and work with some of the “common” human trait examples.