Ch 15 Genetics Part II
Non-mendelian Inheritance and Chromosomal
Abnormalities
Non-Mendelian Inheritance
When a heritable phenotype is NOT controlled
by one gene with two alleles, only
Examples?
1. When alleles are not completely dominant or recessive
Incomplete dominance
Codominance
2.When a gene has more than two alleles
Multiple alleles
3. When a gene produces multiple phenotypes
Pleiotropic
The Spectrum of Dominance
Complete dominance:
- when heterozygous and dominant homozygous
phenotypes are identical
Incomplete dominance:
- phenotype of F1 hybrids is between phenotypes of
parental varieties
Codominance:
- when two dominant alleles affect the phenotype in
separate, distinguishable ways
LE 14-10
Incomplete
dominance
P Generation
Red
CRCR
White
CWCW
CR
Gametes
CW
Pink
CRCW
F1 Generation
Gametes
1
1
F2 Generation
2
CR
2
CR
1
2
1
CW
Sperm
2
CW
Eggs
1
1
2
2
CR
CRCR
CRCW
CRCW
CWCW
CW
Carry out
an F1 cross
an a Punnett
square.
What causes these phenotypes?
C gene: encodes an enzyme that catalyzes the
formation of red pigment
CR allele: normal activity
CW allele: mutant gene that encodes non-functional enzyme
Explain red, white and pink
Example of both: and Multiple alleles and codominance
codominance
Explanation of blood cell type
I gene: encodes enzyme that adds certain carbohydrates to the
exterior surface of RBCs
IA: adds “A” carbohydrates
IB: adds “B” carbohydrates
IO: defective enzyme; no carbohydrates added
Pleiotropy
•
When one gene has multiple phenotypic effects
•
For example, pleiotropic alleles are responsible for the multiple
symptoms of certain hereditary diseases, such as sickle-cell
disease
What are symptoms (phenotypes) of sickle-cell disease?
Epistasis
• When a gene at one locus alters the phenotypic expression
of a gene at a second locus
LE 14-11
Epistasis
BbCc
BbCc
Sperm
1
1
4
BC
1
4
bC
1
4
1
Bc
4
bc
4
BC
BBCC
BbCC
BBCc
BbCc
4
bC
BbCC
bbCC
BbCc
bbCc
4
Bc
BBCc
BbCc
BBcc
Bbcc
4
bc
BbCc
bbCc
Bbcc
bbcc
B=black
b=brown
1
C=pigment deposition
c=no pigment deposition
1
1
9
C/c is epistatic to B/b.
16
3
16
4
16
Polygenic Inheritance
When two or more genes affect a single phenotype
Examples
Often quantitative traits such as height and skin color
Trait varies in a bell shape curve in a population
LE 14-12
Polygenic effect
AaBbCc
What correlation
exists between
the alleles and
skin color?
AaBbCc
aabbcc Aabbcc AaBbcc AaBbCc AABbCc AABBCc AABBCC
20/64
More dominant alleles
Fraction of progeny
15/64
6/64
Darker skin
1/64
Additive effect
Increasing skin darkness
Environmental Impact
• Phenotype is influenced by environmental factors.
• For example, what environmental factors influence skin color
Norm of reaction
the range of phenotypes from a genotype in any given
environment.
Nature and Nurture
Hydrangea: a flowering woody shrub
Grown in acidic soil
Grown in alkaline soil
• Multifactorial effects
influenced by many genes and environmental
factors
What diseases might be considered multifactorial?
Heart disease, high blood pressure,
diabetes, cancer
Human traits: determining mode of inheritance and frequency
Disadvantages as genetic model system
Unethical as an experimental model
system
Slow generation time
Low numbers of offspring
Advantages
Oral and written histories, medical records
Ability to construct retrospective pedigrees
Abiltiy to predict future probability of inheritance
LE 14-14a
Ww
ww
ww
Ww ww ww Ww
WW
or
Ww
Widow’s peak (WW
Ww
Ww
ww
Dominant trait (widow’s peak)
Second generation
(parents plus aunts
and uncles)
Third
generation
(two sisters)
ww
or Ww)
First generation
(grandparents)
No widow’s peak
(ww)
Pedigree
Problems
Female
Male
LE 14-14b
First generation
(grandparents)
Second generation
(parents plus aunts
and uncles)
Third
generation
(two sisters)
Attached earlobe
Recessive trait (attached earlobe)
Free earlobe
LE 14-14b
First generation
(grandparents)
Second generation
(parents plus aunts
and uncles)
Ff
FF or Ff ff
Third
generation
(two sisters)
Attached earlobe
Recessive trait (attached earlobe)
Ff
ff
ff
Ff
Ff
ff
FF
or
Ff
Ff
ff
Free earlobe
Recessive Autosomal Inherited Disorders
• Detectable in individuals homozygous for the allele
• Heterozygous individuals are phenotypically normal;
carry one recessive allele; called carriers
Example: Cystic Fibrosis
Cystic Fibrosis
• Frequency
– One out of every 2,500 people of European descent
Most frequent genetic disease in US (carrier frequency 1 in 20)
• Mutation in cystic fibrosis allele
• - gene encodes CF transmembrane transporter
– Causes defective or absent chloride transport channels in
plasma membranes--> high Na+ & Cl- excretion
• Symptoms
–
–
–
–
Mucus buildup in some internal organs
abnormal absorption of nutrients in the small intestine
prone to infections
lethal
Do some crosses
Most defective alleles are recessive.
Why?
Is there a practical
reason?
If defective dominant allele:
- Immediate decrease in fitness
-Individuals who have the defective dominant allele
likely won’t survive or pass on this allele.
Recessive alleles
Favored
No detrimental effect in heterozygous state
Individuals homozygous for the recessive mutant CF
allele tend to die before childbearing age.
What effect will that have on the frequency of
the mutant allele in the population?
Should go down because it reduces
fitness(ability to reproduce) and eventually
disappear.
Why is the mutant CF still so prevalent?
Hypothesis: correlates with distribution of tuberculosis.
CF carriers may have been more resistant to TB infection due
to elevated of levels of lung mucous.
Mating of Close Relatives
• Consanguineous matings (Inbreeding)
Increased likelihood of genetic disorders
Why?
Higher probability of two recessive alleles
occurring in homozygous state
Laws forbid marriage between first cousins or closer.
Dominant-Autosomal Inherited Disorders
• Achondroplasia
– Form of dwarfism, arrested growth of long bones
– Dominant
– Lethal when homozygous
• Huntington’s disease (dominant autosomal)
–
Degenerative disease of the nervous system
–
No obvious phenotypic effects until about 35 to 40 years of
age
Implications: not selected against
phenotype appears after child bearing years
allele remains in population
Genetic Counseling & Screening:
Under what circumstances might it be of value to
undergo genetic testing?
Abnormal Chromosome Number
Can produce distinctive phenotype
Mechanism
• Meiotic Nondisjunction:
– Tetrads or chromatid sisters fail to separate during
anaphase I or II
LE 15-12
Meiosis I
Nondisjunction
Meiosis II
Nondisjunction
Gametes
n+1
n+1
n–1
n–1
n+1
n–1
n
Number of chromosomes
Nondisjunction of homologous
chromosomes in meiosis I
Nondisjunction of sister
chromatids in meiosis I
n
Abnormal Chromosome Number
Result of Nondisjunction
• Aneuploidy
- Some gametes receives too many chromosomes
- Others not enough
- At fertilization, zygote has abnormal chromosome
number
Analyze karyotype
Sex?
Other?
Down Syndrome
• Aneuploid condition --> three copies of
chromosome 21
•One out of every 700 children born in US
•Frequency of Down syndrome increases with
mother’s age
• Trisomic zygote:
– three copies of a particular chromosome
• Monosomic zygote:
– one copy of a particular chromosome
Polyploidy
– condition in which an organism has more than two
complete sets of chromosomes
Polyploid rodent: tetraploid
T. barrerae
LE 15-14
Other abnormalities: Chromosome breakage:
A deletion removes a chromosomal
segment.
A duplication repeats a segment.
An inversion reverses a segment
within a chromosome.
A translocation moves a segment
from one chromosome to another,
nonhomologous one.
Deletion
Duplication
Inversion
Reciprocal
translocation
Fetal Testing
• Amniocentesis
– the liquid that bathes the fetus is removed and
tested
•Chorionic villus sampling (CVS)
– a sample of the placenta is removed and tested
•Other techniques
– ultrasound and fetoscopy, allow fetal health to be
assessed visually in utero
LE 14-17a
Amniocentesis
Amniotic
fluid
withdrawn
Fetus
A sample of
amniotic fluid can
be taken starting at
the 14th to 16th
week of pregnancy.
Centrifugation
Placenta
Uterus
Cervix
Fluid
Fetal
cells
Biochemical tests can be
performed immediately on
the amniotic fluid or later
on the cultured cells.
Fetal cells must be cultured
for several weeks to obtain
sufficient numbers for
karyotyping.
Biochemical
tests
Several
weeks
Karyotyping
LE 14-17b
Chorionic villus sampling (CVS)
A sample of chorionic villus
tissue can be taken as early
as the 8th to 10th week of
pregnancy.
Fetus
Suction tube
inserted through
cervix
Placenta Chorionic villi
Fetal
cells
Biochemical
tests
Several
hours
Karyotyping
Karyotyping and biochemical
tests can be performed on
the fetal cells immediately,
providing results within a day
or so.
Newborn Screening
Simple genetic tests routinely performed in most
hospitals in the United States
Example
•Metabolic disorders such a phenylketonuria (PKU)
-Autosomal recessive (Chromosome 12)
-non-functional enzyme (phenylalanine hydroxylase)
Inability to break-down essential amino acid phenylalanine-->
•build-up in blood causes mental retardation
–Controlled by diet if caught early