Chapter 4: Modification of

Mendelian RatiosHonors Genetics 2012-2013

MENDEL’S POSTULATES

#1: Unit factors come in pairs.#2: Unit factors have either a dominant or recessive form.#3: Unit factors segregate/ separate during gamete formation.#4: Unit factors assort independently from one another.

Chapter 3 Lessons

#1: Chromosomes come in pairs.#2: GENES have either a dominant or recessive form.#3: Chromosomes segregate/ separate during gamete formation.#4: Chromosomes assort independently from one another.

• Mendel’s postulates for OTHER INHERITANCE PATTERNS do NOT hold true in all respectsThese both hold TRUE for other types of inheritance.

• #3: Unit factors segregate/ separate during gamete formation.

• #4: Multiple unit factors assort independently from one another.

These postulates DO NOT.• #1: Unit factors come in pairs. • #2: Unit factors have either a dominant or recessive form.

Chapter 3 Lessons

• Alleles are alternative forms of the same gene.• Wild-Type Allele

• Appears most frequently in a population• Arbitrary designation of NORMAL• Often DOMINANT• Used as the standard which all alterations/mutations are

compared.• Mutant Allele

• Contains modified genetic information.• Specifies an altered gene product.

• Loss-of-Function• Mutation that results in reduced function of a protein

• Null Allele• Mutation that results in COMPLETE loss of function in

proteins• Gain-of-Function

• Mutation that results in increased function of a protein

4.1: Alleles Alter Phenotypes in Different Ways

4.2: Geneticists Use a Variety of Symbols for Alleles

• Mendel Abbreviations• Dominant allele = capital letter of trait of interest• Recessive allele = lowercase letter of trait of

interest• Work with Drosophila melanogaster (fruit fly)

• Mutant allele = lowercase letter if recessive; capital letter if dominant.

• Wild type allele = uses same letter designation with superscript +

• A slash (/) between the letters designates the location of the allele on homologous chromosomes.

• Cross between parents with contrasting traits may produce offspring with intermediate phenotypes.

• Occurs when the phenotype is controlled by a single gene with two alleles, neither of which is dominant.

• Because there is no dominant trait, abbreviations can vary:• Red = R1 / White = R2 R = Red• White = W1 / Red = W2 W = White• Red = CR / White = CW C = Color

4.3: Neither Allele is Dominant in Incomplete (Partial) Dominance

Snapdragons:Red + White = Pink

Red = CR / White = CW

Incomplete/Partial Dominance

Incomplete/Partial Dominance

Human Example:•NORMAL have 100% activity of the affected enzyme.•CARRIERS have 50% activity of the affected enzyme.•AFFECTED have 0% activity of the affected enzyme.

QUESTION #1, PAGE 87

IN SHORTHORN CATTLE, COAT COLOR MAY BE RED, WHITE, OR ROAN. ROAN IS AN INTERMEDIATE PHENOTYPE EXPRESSED AS A MIXTURE OF RED AND WHITE HAIRS. THE FOLLOWING DATA ARE OBTAINED FROM VARIOUS CROSSES:

RED X RED = ALL REDWHITE X WHITE = ALL WHITERED X WHITE = ALL ROANROAN X ROAN = ¼ RED; ½ ROAN, ¼ WHITE

HOW IS COAT COLOR INHERITED? WHAT ARE THE GENOTYPES OF PARENTS AND OFFSPRING FOR EACH CROSS?

RED X RED = ALL REDCR/CR X CR/CR = CR/CR

WHITE X WHITE = ALL WHITECW/CW X CW/CW = CW/CW

RED X WHITE = ALL ROANCR/CR X CW/CW = CR/CW

ROAN X ROAN = ¼ RED; ½ ROAN, ¼ WHITECR/CW X CR/CW = CR/CR, CR/CW, CW/CW

CR CR

CW CWCR CWCR

CW CWCR CWCR

CR CW

CR CRCR CWCR

CW CRCW CWCW

Incomplete:•Phenotype expression different than either parent.•MIXTURE

Codominance:•Phenotype expression that is equal to BOTH parent’s phenotypes.

Incomplete/Partial vs. Codominance

4.4: Codominance and MN Blood Groups• Joint expression of BOTH alleles.• In humans, 2 forms/alleles for the

glycoprotein are present on the red blood cell surface, M and N

• The gene for the glycoprotein is located on chromosome #4.

• The 2 alleles are designated LM and LN

Genotype Phenotype

LMLM M

LMLN MN

LNLN N

4.5: ABO Blood Groups: Multiple Alleles• Identified by Landsteiner in 1901.• The alleles for ABO blood groups are located on

chromosome 9.

4.5: ABO Blood Groups• 3 alleles• I = isoagglutinogen; agglutination means to

clump.• IA = A antigens; B antibodies• IB = B antigens; A antibodies• IO = NO antigens; A and B antibodies

Genotype Antigen Phenotype

IAIA AA

IAIO/IAi A

IBIB BB

IBIO/IBi B

IAIB A and B AB

IOIO/ii NO antigens O

Bombay Phenotype

• Rare cases of incomplete formation of carbohydrates that form the A and B antigens, called the H substance.

• Results in an O phenotype, although they do not have O blood; they will still have A and/or B antigens on their red cell surface.

• Issues arise at the time of transfusion; if they test RBC’s only in the patient, they could receive incompatible blood and will suffer a transfusion reaction.

• See pedigree, Page 64

Rh Factor• Rh inheritance (+/-) follows traditional

Mendelian Dominant/Recessive inheritance patterns.

• Rh + is Dominant• Rh – is Recessive• Rh pos can be homozygous dominant or

heterozygous (+/+ or +/-)• Rh neg must be homozygous recessive (-/-)

• Referenced as the D antigen• Rh + = D• Rh - = d

A man is suing his wife for divorce on the grounds of infidelity. Their first child and second child, whom they both claim, are blood groups O and AB, respectively. The third child, whom the man disclaims, is blood type B.

(a)Can this information be used to support the man's case?

MN/ABO Practice

(a)Can this information be used to support the man's case? Child #1: IOIO

Child #2: IAIB

Child #3: IBIB or IBIO

MOTHER’S GENOTYPE: IAIO

FATHER’S GENOTYPE: IBIO

A man is suing his wife for divorce on the grounds of infidelity. Their first child and second child, whom they both claim, are blood groups O and AB, respectively. The third child, whom the man disclaims, is blood type B.

(b) Another test was made using the M-N blood group system. The third child was group M, the man was group N. Can this information be used to support the man's case?

MN/ABO Practice

(b) Another test was made using the M-N blood group system. The third child was group M, the man was group N. Can this information be used to support the man's case?

Child 3: LMLM

Father: LNLN

Impossible for the man to be the child’s father due to the difference in M and N antigen on the red cell surface.

4.6: Lethal Alleles Represent Essential Genes• Mutations resulting in the production of

a gene product that is nonfunctional can often be tolerated in the heterozygous form.• Behaves as a recessive allele

• If present in the homozygous condition it is considered LETHAL and the organism will not survive.

• The time of death is dependent on when the product is needed.

• Example: Huntington’s Disease• Gradual nervous and motor degeneration• Late-onset

Phenotypes are Often Affected by More Than One Gene

• Gene interaction is when several genes influence a particular characteristic.

• It doesn’t necessarily mean that genes directly interact with each other but that the cell products of gene expression influence a common phenotype.

• Often described as a CASCADE event.• Epigenesis is the increased complexity in

the development of an organ/system and is under the control of one or more genes.• Example: Insect eyes and mammalian ears• A mistake in the CASCADE of events can lead to

mutations and poor development, leading to blindness or deafness.

Epistasis• Expression of one gene/gene pair masks or

modifies the expression of another gene/gene pair.

• Can be antagonistic or complementary• #1: RECESSIVE EPISTASIS:

Epistatic/Hypostatic• Homozygous presence of a recessive allele

prevents/masks the expression of other alleles at a second location.

• The alleles at the first locus are epistatic to the alleles at the second locus.

• The alleles at the second locus are hypostatic to the alleles at the first locus.

• EXAMPLE: Bombay phenotype • The FUT1 gene overrides the expression of the IA and IB

alleles.

Epistasis• #2: DOMINANT EPISTASIS:

• A single Dominant allele at locus 1 influences the expression of the alleles at locus 2.

• EXAMPLE: Squash color; the presence of the dominant A allele for white squash is expressed regardless of what is coded for at the second location. Absence of the A allele will produce either yellow (BB, Bb) or green (bb).

• #3: COMPLEMENTARY GENE INTERACTION:• Two gene pairs COMPLEMENT one another so that at

least one dominant allele must be present from each pair of genes to express a particular phenotype.

• EXAMPLE: Pea flower color; 2 proposed locations/genes for flower color; the presence of at least one dominant allele at either location allows for expression of allele.

EPIGENETICS

•The study of how the genome is influenced by outside factors.

EPIGENESIS•Cascade of events that leads to development of complex structure.•Gene interaction is essential.

EPISTASIS•Expression of one gene or gene pair masks, modifies, or complements the expression of another gene or gene pair.

4-10: Expression of a Single Gene May Have Multiple Effects

• PLEIOTROPY: expression of a SINGLE gene has multiple phenotype effects.

• Marfan Syndrome: • Mutation of fibrillin protein, a necessary

connective tissue protein that provides structural integrity for many body tissues.

• Single m]gene mutation = multiple effects.• Porphyria variegata:

• Mutation in enzyme that breaks down porphyrin, a component of hemoglobin.

• Porphyrins build up in body tissues, causing a wide range of symptoms.

4.11: X-linkage• Covered with Chapter 3 pedigree

Practice.• Refers to genes located ONLY on the X

chromosome.• Female carry 2 copies• Males have only 1 copy• Remember the rules

• In X-linked RECESSIVE pedigrees, affected mothers will have 100% affected sons.

• In X-linked DOMINANT pedigrees, affected fathers will have 100 % affected daughters.

For Quiz:

1) Correct and Review Chapter 4 Quiz2) Review Powerpoints, focus on Vocabulary

#1: Chapter 4#2: Epigenetics

3) Practice Punnett Squares and Pedigrees for Sex-linked (X-linked) traits.4) MN/ABO/Rh Blood Group Practice

Still to finish…• 4.12 Sex-influenced inheritance• 4.13 Environmental Affect of

phenotype expression• 4.14 Extranuclear inheritance