Download Mode of Inheritance

Mode of Inheritance
Genotype and Phenotype
Dominant/Recessive Traits
Polygenic Traits
Multiple Allelic Traits
Dominance Has Degrees
Sex-Linked Traits
HUMAN INHERITANCE
All human phenotypic characters
require the interaction of many loci
Possible modes of inheritance:
Mendelian inheritance
 Polygenic (Quantitative) inherit

Mendelian inheritance

Particular genotype at one locus is both
necessary and sufficient for the character
to be expressed
TERMS:
locus: the location of a gene on a
chromosome
Allele: Different forms of the same
gene, at the same locus on a pair of
homologous chromosomes
Dominant alleles are given capital
(uppercase) letters e.g. A,H.B etc.
 Recessive alleles are given small (lower
case) letters e.g. a,h,b etc

Number of traits with simple modes of
inheritance
HOW MANY LOCI?
HUMAN HAPLOID GENOME




~ 3 billion basepairs
20-25,000 genes in human genome
> 100,000 BP PER GENE?
average protein ~ 500-1000 a.a.

THEREFORE: lots of non-coding material
ALLELIC VARIATION
MUTANT = "abnormal" or "defective" allele

[“mutant” should correctly be applied to a new
allele arising by mutation]
VARIANT = alternative rare alleles
POLYMORPHISM = two or more alleles at
“significant” frequency

(second allele with frequency greater than 0.01)
Genotype
Genotype: the genes present in an individual for a given trait
or characteristic (or represents the actual genes of an individual)
We have two copies of every gene (one maternal allele, one
paternal allele)

if the two alleles of a gene are the same the individual is said to
be homozygous



if both alleles are recessive alleles the individual is homozygous
recessive
if both alleles are dominant the individual is homozygous dominant
if the two alleles are different (i.e. one dominant and one recessive
allele) the individual is heterozygous
Phenotype
Phenotype:
The physical appearance of the
individual or physical trait (e.g., red
hair).



Individuals with the homozygous
dominant genotype have a dominant
phenotype
Individuals with the homozygous
recessive genotype have a recessive
phenotype
Individuals with the heterogeneous
genotype have a dominant phenotype
Dominant/Recessive Traits
Forming the Gametes

During oogenesis and spermatogenesis
(collectively, gametogenesis), chromosome
number is reduced to half, and each gene pair
for a trait is separated, so that the offspring
receives one gene for each trait from each
parent.
Figuring the Odds


A parent who is homozygous dominant or
homozygous recessive for a trait can pass on
only one type of gamete in each case.
Heterozygous parents can pass on either the
dominant or the recessive gene for a given trait.
A Punnett square is useful for determining the
possible outcomes of a genetic cross.
EXAMPLE Ear lobes
E dominant allele for unattached ear lobes
e Recessive allele for attached ear lobes
(in any example always say what the letters represent)
genotype EE dominant phenotype unattached ear lobes
genotype ee
recessive phenotype attached ear lobes
genotype Ee dominant phenotype unattached ear lobes
A Punnett square
Example 1
Heterozygous - by Heterozygous cross
Egg
E
Sperm
e
E
EE Ee
e
Ee ee
Phenotypic Ratio 3:1
Phenotypes
Unattached earlobes
Attached earlobes
A cross of the gametes of two heterozygotes
results in a
25% chance that the offspring will be
homozygous recessive, a
50% chance that the offspring will be
heterozygous, and a
25% chance that the offspring will be
homozygous dominant.
Each offspring has a 25% chance of being
homozygous recessive or of being
homozygous dominant.
Genotypic ratio:
1:2:1
1 EE: 2Ee :
1ee
Mother
E
e
Father E
EE
Ee
e
Ee
ee
Example 2
Heterozygous - by
homozygous recessive cross
Mother
Father
E
e
e
e
Ee
Ee
ee
ee
Give phenotypes of parents
Give genotype of parents
State gametes produced
Make punnet square
Genotypic Ratio 1:1
1 Ee : 1 ee
Phenotypic Ratio 1:1
1 Unattached ear lobes : 1 attached ear lobes
1 dominant phenotype: 1 recessive phenotype

A cross of the gametes of two individuals
who are both homozygous for a trait results
in a …………..of having an offspring who is
homozygous for the trait.
100% chance
Inherited genetic diseases
Autosomal dominant diseases
Autosomal recessive diseases
X-linked recessive diseases
Autosomal dominant
inheritance
All affected individuals should have an affected parent
Both sexes should be equally affected
Roughly 50% of the offspring of an affected individual
should also be affected
Huntington’s disease and Neurofibromatosis.
Chromosome 17
Neurofibromatosis




Neurofibromatosis is inherited as an autosomal
dominant.
People with this condition develop benign
neurofibromas under the skin and in various
organs.
The effects can range from mild to severe, and
some neurological impairment if possible.
The gene for this trait is a nested gene on
chromosome 17
Chromosome 4
Huntington Disease



Huntington disease is also inherited as an autosomal
dominant and is characterized by progressive neurological
degeneration of brain cells,
Further, it is a late acting gene, and often is diagnosed after
the person has reproduced
The gene causing Huntington disease was cloned in 1993,
and a marker is now available

The gene is a nucleotide triplet repeat (to over 100 times), and
the degree of the repeat appears to be related to severity and
age of onset of symptoms No treatment exists, and death
occurs a decade or so after the symptoms appear.


Most genetic diseases are inherited
as autosomal recessive traits
Inborn errors of metabolism typically
result in prenatal or early death
Autosomal Recessive
Inheritance
Usually there is no previous family history
The most likely place to find a second
affected child is a sibling of the first
Autosomal recessive
Inbreeding increases the chance of observing
an autosomal recessive condition
E.g. Cystic fibrosis, sickle cell disease, Tay
Sachs disease and PKU.
Tay-Sachs Disease




Tay-Sachs disease is inherited as an autosomal
recessive.
A lysosomal enzyme is missing, which results in
improper lipid metabolism in cells, particularly those
of the nervous system
Between four and six months of age, an affected
infant shows neurological impairment. The child
gradually becomes blind, helpless, and paralyzed,
and usually dies by age four.
Tay-Sachs gene is located on chromosome 15. This
disease is most prevalent in Jewish people from
central and eastern European descent.
Chromosome 7
Cystic Fibrosis
It is the most common lethal genetic
disease among Caucasians.
 Mucus in the lungs and digestive tract is
thick and viscous, making breathing and
digestion difficult
 The cystic fibrosis gene is located on
chromosome 7

Chromosome 12
Phenylketonuria (PKU)
It is the most commonly inherited metabolic
disorder to affect nervous system
development .
 The PKU gene is located on chromosome
12

Polygenic Traits
Polygenic traits are those governed by
more than one gene pair. Several pairs
of genes may be involved in
determining phenotype.
Skin Color: The inheritance of skin
color, determined by an unknown
number of gene pairs, is a classic
example of polygenic inheritance.
Polygenic Disorders

Many human traits, like allergies,
schizophrenia, and cleft lip, appear to be
inherited as polygenic traits. The
expression of some genes is subject to
environmental influences (e.g., a child
allergic to ragweed will never express that
trait while living in the Arctic).
Multiple Allelic Traits
In multiple alleles, more than two
alternative types exist for a gene pair.
ABO blood grouping is an example.
ABO Blood Types


The ABO blood grouping represents
surface marker proteins on red blood cells.
A person can have a gene for an A marker
or a B marker, which are codominant, or
lack an A or B marker, designated type O,
which is recessive.
Human ABO blood types can then be type
A (which can be AA or AO), type B (BB or
BO), type AB (AB), or type O (OO).
Blood Types
There are three different alleles
for human blood type:
Blood types For simplicity,
we call these
IA
A
IB
B
i
O






The ABO blood group is a multiple allele at a single
locus
Persons with type A blood have the allele IA which
codes for the synthesis of a glycoprotein (antigen
A) on the surface of the red blood cells
Persons with the allele IB produce antigen B;
persons with both alleles produce both antigens
(AB)
Persons with the allele io do not produce either
antigen; this allele is recessive to both A and B
Other blood "types" are inherited independently
Use of blood types can only disprove paternity

Today, DNA fingerprinting and tissue typing are more
accurate tests
Since there are three different alleles, there are a total of six
different genotypes at the human ABO genetic locus.
Allele from Allele from Genotype of Blood types of
the mother the father
offspring
offspring
A
A
AA
A
A
A
B
B
O
A
AB*
AO
AB*
AB
A
AB
B
B
B
O
BB
BO
B
B
O
O
OO
O
Rh alleles control the expression of
other red blood cell antigens
The Rh allele is named for the rhesus monkey
The Rh system includes about 8 antigens; antigen D is
the most important
The majority of persons of western European descent
are Rh positive (possessing antigen D on their red blood
cells)
Rh positive persons are homozygous dominant or
heterozygous
Rh incompatibility may occur when a woman is Rh
negative and the fetus is Rh positive

Erythroblastosis fetalis results from a sensitized pregnant
woman’s antibodies passing into the fetal blood, and may
cause fetal death
After a first childbirth, women at risk are now given a
RhoGAM shot to prevent sensitization
Exceptions to clear cut
Mendelian inheritance
Lethal alleles
Incomplete dominance
Codominance
Silent alleles
Dominance Has Degrees
Patterns of dominance often go beyond
simple dominant or recessive traits.
a. Codominance means that both alleles
are expressed (type AB blood).
 b. Incomplete dominance is exhibited when
the heterozygote shows not the dominant
trait but an intermediate phenotype,
representing a sort of blending of traits
(e.g., skin color or hair type).

Sickle-Cell Disease
Sickle-cell disease is an example of
incomplete dominance. An individual with
two genes for normal hemoglobin has
normal hemoglobin.
 A heterozygote has a normal gene and a
gene for sickled hemoglobin.
 An individual with two sickling genes has
sickle-cell disease.
 What may have maintained this apparently
detrimental gene in equatorial Africa is that
heterozygotes for this trait have a marked
resistance to the malarial parasite
prevalent in the region.

Sex-Linked Traits
Sex-linked traits are genes (traits) carried
most frequently on the X chromosome. (The
Y chromosome is too small.)
X-Linked Alleles

In X-linked traits, the gene is carried on the X
chromosome. Since males have only one copy of
the X chromosome, they show the phenotype for
the allele they possess and are thus much more
likely than females to show a recessive trait.

A female must have two copies of a
recessive trait (one on each X
chromosome) to display it. If a female has
only one copy of a recessive gene, she is
said to be a carrier and will pass the trait
on to 50% of her sons, on average.
Some Disorders Are X-Linked
A. Color Blindness
 Three types of cones are in the retina:
those that detect red, those that detect
green, and those that detect blue. Genes
for blue cones are autosomal; those for red
and green cones are on the X
chromosome.
 Males are much more likely to have
red/green colorblindness than are females.
B. Muscular Dystrophy
 Duchenne muscular dystrophy is X-linked
and is characterized by progressive muscle
deterioration during childhood. .
C. Hemophilia




Hemophilia (bleeder's disease) can be traced to Queen
Victoria of England and is characterized by the absence or
minimal presence of one of two different clotting factors.
Again, males are much more prone to this trait than females
and often require blood transfusions.
Hemophilia A is the most common form of hemophilia
Hemophilia A was common among the royal families in
Europe
Currently, hemophiliacs have a high HIV infection rate due to
the previous treatment by blood transfusions and injections
of Factor VIII
Some Traits Are Sex-Influenced

Some traits carried on autosomes such as
male-pattern baldness, can be influenced
by gender. In this instance, the male
hormone testosterone is the culprit.
Some genetic diseases are inherited
as X-linked recessive diseases
Hemophilia A is an X-linked recessive
disorder that affects blood clotting




Hemophilia A is the most common form of
hemophilia
Hemophilia A was common among the royal
families in Europe
Currently, hemophiliacs have a high HIV infection
rate due to the previous treatment by blood
transfusions and injections of Factor VIII
Genetic counselling
Genetic counselors educate
people about genetic diseases


Genetic counselors can only give the
probability of a certain condition
occurring in the offspring
The probabilities remain constant
with each sequential pregnancy
Pedigree Charts

Pedigree charts are a way of making a family
tree and indicate which individuals are affected
by a trait. Since recessive and dominant traits
exhibit different patterns of inheritance, pattern
of inheritance can be partially determined by
examining a pedigree chart.

Genetic counselors use pedigree charts
and a variety of other means to predict the
likelihood of two parents producing an
offspring with a genetic disorder. Some
tests can be run during pregnancy.
Both genetic and environmental
factors cause birth defects
Birth defects are those that are
present at birth, and may be genetic
or not


Maternal rubella and alcohol
consumption may cause non-genetic
birth defects
Some birth defects can be detected
before birth


Amniocentesis

Amniocentesis involves sampling the fluid of
the amniotic sac, which contains shed
epidermal cells of the fetus

Chorionic villus sampling (CVS) samples fetal
cells of the placenta and can be done earlier in
pregnancy
Amniocentesis

Amniocentesis involves sampling the fluid of the
amniotic sac, which contains shed epidermal cells of the
fetus






Positioning of the needle is done via ultrasound imaging
After several weeks of laboratory culture, cells of the fetus
can be visualized
Karyotyping can indicate Down syndrome and other
aneuploidies
The amniotic fluid may also be chemically analyzed to
detect disorders such as Tay-Sachs disease and spina
bifida
Other tests require the use of genetic engineering methods
The main drawback of amniocentesis is that it detects
mostly incurable defects and can be done relatively late in
the pregnancy
Gene replacement therapy is being
developed for several genetic diseases
One strategy involves introduction of a normal
gene into a fertilized egg
Another strategy is to introduce the normal
gene into body cells of a diseased person

This is the focus of most current research, and
viruses are often used as vectors
The first gene replacement therapy was for
persons with severe combined immune
deficiency syndrome (SCIDS), and has been
relatively successful
Much natural variation exists in the
human population



Humans have several genetically
determined blood groups
Quantitative traits are controlled by
polygenes
Many common physical
characteristics are inherited
The Human Genome Project is
studying all human genes
The Human Genome Project began in
the late 1980s
The goal is to sequence the 3 billion
base pairs in the human haploid
genome



It was initially hoped to be completed by
the year 2003, but that is unlikely