neo-Mendelian Genetics After re-discovery, Mendel’s postulates were applied to many genetic...

neo-Mendelian Genetics

• After re-discovery, Mendel’s postulates were applied to many genetic traits,

• However, some genetic data did not conform to the

expected results,

Continuous Variation

vs.

Discontinuous Variation

Alleles

• Alleles are alternate forms of the same gene,

• Wild-type allele: the allele that occurs most frequently in the population,

– ‘normal’,– usually dominant.

Wild-type vs. ?

• wild-type alleles are responsible for the most common phenotype,

• mutant alleles: contain modified genetic information, compared to wild-type,

• mutant alleles are responsible for mutant phenotypes.

Dominance(not always complete)

xcomplete

xincomplete

xcodominant

phenotypes

A1 dom. A2A2 rec. A1

A2 dom. A1A1 rec. A2

xcomplete

A2 A2 A1 A2 hybridsA1 A1

A1 A1 A2 A2

to each other

to each other

Incomplete Dominance

…expression of heterozygote phenotype resulting in offspring that do not resemble either parent,

– often, offspring phenotype is intermediate between those of the parents.

xincomplete

A2 A2 A1 A2 hybridsA1 A1

A1 and A2 are incompletely dominant in regards to each other.

R1: red R2: white

Genotypes Phenotypes

Phenotypic Ratio is Equal to Genotypic Ratio

Genotypes Phenotypes

R1 R1 R1 R2 R1 R2 R2 R2

Genotype: 1:2:1

Phenotype: 3:1R2 dom R1

Genotype: 1:2:1

Phenotype: 3:1R1 dom R2

Genotype: 1:2:1

Phenotype: 1:2:1incompletelydominant

F2 Possible Ratios

Codominance

…expression of heterozygote phenotype resulting in offspring that resemble both parents,

– both parental traits show up equally and fully in the offspring.

xcodominant

A2 A2 A1 A2 hybridsA1 A1

A1 and A2 are codominant to each other.

CS spotted CD dotted

CS CS CD CD

P x

CS CD

F1

CS CS CD CDCS CD CS CD

F2

codominantg: 1:2:1

p: 1:2:1

g: 1:2:1

p: 3:1 CS dom CD

CS CS CD CDCS CD CS CD

g: 1:2:1

p: 1:2:1incompletedominance

F2 Possible Ratios

Fig. 2-20

Dominance?Incomplete Dominance?Co-Dominance?

Think about this.

Lethal Alleles

• Essential alleles that if not expressed in a sufficient amount, result in lethality,

– recessive lethal allele: homozygous recessive

individuals die, heterozygous individuals live,

– dominant lethal allele: homozygous recessive

individuals die, heterozygous individuals die.

Recessive Lethal Alleles

A a

A

a

AA Aa

Aa aa

– recessive lethal allele: homozygous recessive

individuals die, heterozygous individuals live,

Modifies Ratio:

2:1 Genotypic Ratio

all wild-type

Lethality Definitions

• Lethal phenotype: doesn’t reproduce*,

– *late onset lethal phenotypes,

• Lethal allele: expression, or lack of expression causes death.

t: no tail

T: wild-type

TT: tailed cat Tt: no tail tt: lethal

recessive lethal?

t: Manx

T: wild-type

TT: tail cat Tt: no tail tt: lethal

Lack of T results in death, t is recessive……t does not result in death when T is present.

what about lethality?

Dominant Lethal Alleles

A a

A

a

AA Aa

Aa aa

– dominant lethal allele: homozygous recessive

individuals die, heterozygous individuals die,

The dominant allele is not lethal!

The recessive allele is the lethal, it acts as a dominant lethal in the heterozygote.

Huntington’s Disease

It is spoken of by those in whose veins the seeds of the disease are know to exist, with a kind of horror, and not at all alluded to except through dire necessity.

- George Huntington, 1872

Huntington’s

• Neurological and movement disorder with typical onset at about age 40,

H: wild-type h: Huntington

• On March 23, 1993, the Huntington's disease gene was discovered near the tip of chromosome 4. Discovery of the gene has led to direct, genetic testing for the disease.

• Gene therapy and other programs are underway and are highly encouraging.

HH: wild-type Hh: late onset lethal

hh: lethal

Dominant Lethal Alleles

H h

H

h

HH Hh

Hh hh

– dominant lethal allele: dominant in regards to

lethality,

H: normal

h: Huntington’s

lethality is dominant.

Gamete Lethality1:1 ratio

• How could this happen, how would you test your hypothesis?

Tt x Tt

1/4 TT 1/4 Tt 1/4 Tt 1/4 tt

Reciprocal Crosses

pollen lethal?

aha3-1 x wt

TT Tt

TT Tt

T t

T

T

ovule lethal?

aha3-1 x wt

TT TT

Tt Tt

T T

T

t

YES NO

wildtype Aha3-1

Alexander’s Stain

Pollen

Aha3

More than Two Alleles?

Antigens and Antibodies

Antibody: protein with the ability to bind to specific molecules...

Antigen: substance that stimulates an immune response, especially the production of antibodies. Antigens are usually proteins and/or polysaccharides.

Cell membrane

ABO and Allelic Interactions

• ABO blood groups,

– A and B antigens are on the surface of red blood cells,

• if you add an A-antibody to blood with type A antigens, the blood co-aggulates,

• if you add a B-antibody to blood with type B antigens, the blood co-aggulates,

• There are four recognizable phenotypes,

A B AB O

Antigens, Antibodies and Coagulation

...once the antibody binds, the molecules coagulate, or clump together.

I = Isoagglutinogen

...a gene with three alleles,

...codes for proteins that modify plasma membrane bound, glycosylated proteins in red blood cells.

A B O

IA

IA codes for a protein that specifically adds a N- acetylgalactosamine

IB

IB codes for a protein that adds a galactose

i (ii)

no carbohydrate

O

ii

3 Alleles(4 phenotypes)

A

IA IA

IAi

B

IB IB

IBi

AB

IA IB

O

ii

IA and IB are Codominant IA and IB are Dominant to i

A

IA IA

IAi

B

IB IB

IBi

AB

IA IB

IA and IB are Codominant IA and IB are Dominant to i

Know Genotype/Phenotype

Bombay Phenotype

How can this be?

An entire H substance must be present to permit the I gene product to bind a sugar.

H Substance

H gene product catalyzes this bond.

A B O

IA

H_

ii

H_

IA

H_

No Antigenicity

Genotype hh

IA IA

IAi

IB IB

IBi

IA IB ii

Bombay Phenotype

How can this be?

Epistasis

…a gene interaction in which the effects of one gene hides the effects of another gene,

– epistatic: gene A genotype hides gene B phenotype,

– hypostatic: gene B phenotype is hidden by gene A genoype.

ABO and H Alleles

• epistatic: hh genotype hides AB phenotypes, – h gene is epistatic to I gene,

• hypostatic: AB phenotypes are hidden by hh genotypes,– I gene is hypostatic to h gene.

Epistasis

“Classes” are masked, or “underrepresented”.

Study this chart.

Genetics: …in the News

Penetrance

…the frequency at which individuals with a given genotype manifest a specific phenotype.

• 4 of 6 dogs, or 66% of the population shows the phenotype, at some level,

• penetrance is usually referred to as a percentage.

all the same genotype

Penetrance

Expressivity

…the degree, or range in which a phenotype of a specific genotype is expressed.

• range of phenotypes

• expressivity may be referred to as a percentage, or another quantifiable measure.

all the same genotype

Expressivity

Pentrance? Expressivity?

Pentrance? Expressivity?

Pentrance? Expressivity?

Pentrance? Expressivity?

Complementation

• process by which an allele of each of two mutant genes makes up for the defect in the other gene.

You Find Two Mutants With a Similar Phenotype

Are they the Same Genotype?

Possible Physiology

Enzyme A

Enzyme B

Enzyme A

Enzyme B

Enzyme A

Enzyme B

Complement

a

|

|

B

a

|

|

B

A

|

|

b

A

|

|

b

x

A

|

|

b

a

|

|

B

Two genes

Fail to Complement

A

|

|

b

A

|

|

b

A

|

|

b

A

|

|

b

x

A

|

|

b

A

|

|

b

1 gene

a

b

c

de

f

Assignments

• Read from Chapter 3, 3.6 (pp. 100-106),

• Master Problems…3.12, 3.15, 3.20,

• Read Chapter 4, 4- 4.4,

• Chapter 4, Problems 1, 2,

• Questions 4.1 - 4.4, 4.6, 4.7, 4.9, 4.11 -4.14, 4.19 - 4.20 a,b,c,d.