Transcript Chapter 7: Human Genetics - Father Michael McGivney

Chapter 7: Human Genetics
Autosomal Dominant Inheritance
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Autosomal dominant
inheritance occurs when
one copy of an allele is
sufficient for expression
of a trait and the gene is
located on one of the 22
autosomes.
Each affected person has at least one affected parent. An
affected person has a 50% chance of passing the trait to a
child.
Males and females are equally likely to be affected. Two
affected people can have an unaffected child.
Autosomal Dominant Disorders
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Progeria: characterized by an appearance of
accelerated aging in children, affects 1 in 8
million newborns
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Huntington’s Disease: degenerative brain
disorder, slowly diminishes the affected
individual’s ability to walk, think, talk and reason
 dementia
Autosomal Recessive Inheritance
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Autosomal recessive
inheritance occurs when two
copies of an altered gene
located on one of the
autosomes must be present for
an individual to be affected
with the trait or condition
determined by that gene.
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An affected individual (homozygote) has two parents who are
unaffected but each parent carries the altered gene
(heterozygote).
Males and females are at equal risk for being affected.
Two affected individuals usually produce children all of whom
are affected as well.
Autosomal Recessive Disorders
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Tay-Sachs Disease: individuals lack an enzyme in the
lysosomes of their brain cells needed to break down
lipids. The undigested lipids enlarge and eventually
destroy the brain cells that house them.
Phenylketonuria (PKU): individuals lack an enzyme
that converts Phe to Tyr. Failure of the conversion to
take place results in a buildup of Phe. Through a
mechanism that is not well understood, the excess Phe
is toxic to the central nervous system. This results in
mental retardation and other neurological problems if
not detected early.
Albinism
X-Linked Inheritance
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Most individuals who are affected with the trait or condition in
questions are males.
Mothers of the affected males are carriers and the sisters of
affected males may be either carriers or not carry the gene al all.
The basis for X-linked inheritance is that females have two X
chromosomes and males have only one X chromosome.
Affected males are hemizygous (their one X chromosome has the
mutant allele)
Affected females are homozygous (both X chromosomes have the
mutant allele)
Affected males transmit the gene to all daughters, but not to any of
their sons
The daughters of an affected male will usually be a carrier
(heterozygote) and thus not show the trait (masked)
Sons of heterozygous females have a 50% chance of receiving the
gene and thus expressing the trait or condition
X-linked Disorders
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Colour Blindness
In red-green colour vision deficiency, the
visible spectrum is divided into two parts;
a red segment and a blue segment, separated
by grey or indistinct areas. The amount of grey
or indistinct areas varies according to the severity of the
deficiency.
 Men are mainly affected
 For a woman to be colour deficient, her father must be
colour-blind and her mother must be a carrier
 A defective male always inherits his deficiency from his
mother who usually has normal colour vision is
therefore a carrier of the defect.
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Duchenne Muscular Dystrophy
Involves the wasting away of muscle tissue
 Muscle cells become engorged with fat and they
eventually waste away most individuals suffer from
respiratory failure in their early twenties.
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Human Pedigrees: Working out Inheritance Patterns
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Pedigrees are a convention for keeping track of human genetic traits used to
infer genotype.
Pedigrees are the human equivalent of test crosses.
In a visualization of a pedigree:
males are designated with square symbols.
females with round symbols
lines are drawn to indicated matings, parent-offspring relationships, and
relationships between siblings.
Factors to Consider in Pedigrees
Is the trait located on a sex chromosome or an autosome?
Autosomal – not on a sex chromosome
Sex Linkage – located on one of the sex chromosomes
Y-linked - only males carry the trait.
X-linked (recessive) - sons inherit the disease from normal
parents
How is the trait expressed?
Dominant - the trait is expressed in every generation.
Recessive - expression of the trait may skip generations.
Pedigree
Diagrams: I
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Basic Symbols
Pedigree
Diagrams: II
Basic Symbols for offspring and
the expression of a trait.
The offspring are depicted
below the parents.
Filling the symbol with black
indicates the expression of
the studied trait.
Note that the symbols for non-identical twins and
for identical twins differ by whether they descend
from a common vertical before bifurcating
Pedigrees
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Generations are numbered
from the top of the pedigree
in uppercase Roman
numerals, I, II, III etc.
Individuals in each
generation are numbered
from the left in arab
numberals as subscripts, III1
, III2, III3 etc. For example,
here is a typical autosomal
dominant pedigree with
numbered generations and
individuals.
Marfan’s Syndrome: An Example
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Expressed in both sexes.
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Thus, autosomal.
Expressed in every generation.
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Thus, dominant.
Marfan’s: Genotype the Normal
Individuals
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Assign codes for the alleles.
Code “m” for the recessive normal allele.
 Code “M” for the dominant allele for Marfan’s
syndrome.
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Normal individuals must be “mm.”
Marfan’s: Genotype the Affected
Individuals
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Affected individuals must have at least one
“M.”
Marfan’s: Parent-Offspring Relationships
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Possibilities for #1 and #2: Heterozygote (Mm) or
homozygous for “M?”
If “MM,” all offspring from a normal mate should be
affected.
Therefore, both must be heterozygotes.
Marfan’s: Parental Genotypes Known
“M” must have come from the mother.
 The father can contribute only “m.”
 Thus, the remaining genotypes are “Mm.”
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Albinism: An Example
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Expressed in both sexes at
approximately equal frequency.
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Thus, autosomal.
Not expressed in every
generation.
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Thus, recessive.
Albinism: Genotype the Affected
Individuals
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Assign codes for the alleles.
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Code “A” for the dominant normal allele.
Code “a” for the recessive allele for albinism.
Affected individuals must be homozygous for “a.”
First generation parents must be “Aa” because they
have normal phenotypes, but affected offspring.
Albinism: Genotype the Normal
Individuals
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Normal individuals must have at least one
“A.”
Albinism: Parent-Offspring Relationships
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#1 must transmit “a” to each offspring.
The “A” in the offspring must come from the father.
Normal father could be either heterozygous or
homozygous for an “A.”
Albinism: Parental Genotypes are Known
Both parents are heterozygous.
 Normal offspring could have received an
“A” from either parent, or from both.
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Albinism: One Parental Genotype is Known
Only the genotype of the offspring
expressing albinism are known.
 Normal offspring must have received an
“a” from their affected father.
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Hairy Ears: An Example
Only males are affected.
 All sons of an affected father have hairy
ears.
 Thus, hairy ears is Y-linked.
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Hairy Ears: Female Sex Determination
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All females are XX
Hairy Ears: Male Sex Determination
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All males are XY.
Hairy Ears: Gene on the Y Chromosome
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Code “H” indicates the allele on the Y
chromosome for hairy ears
Hairy Ears: Wild-Type Allele for
Normal Ears
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Code “+” indicates the allele on the Y
chromosome for normal ears.
Hemophilia: An Example
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In this pedigree, only males are affected, and sons do
not share the phenotypes of their fathers.
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Thus, hemophilia is linked to a sex chromosome–the X.
Expression of hemophilia skips generations.
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Thus, it is recessive.
Extensive bruising
of the left forearm
and hand in a
patient with
hemophilia.
Hemophilia:
Expression of the Female Sex Chromosomes
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All females are XX
Hemophilia:
Expression of Male Sex Chromosomes
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All males are XY.
Hemophilia: Genotype the Affected
Individuals
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Assign codes for the alleles.
 Code “H” for the recessive hemophilia allele.
 Code “+” for the wild-type normal allele.
Affected individuals must have an “H” on an X chromosome.
Hemophilia: Father-Daughter
Relationship
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All daughters of an affected father receive
an X chromosome with the “H” allele.
Hemophilia: Genotyping the Normal
Individuals
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Normal individuals must have at least one
X chromosome with the wild-type allele,
“+.”
Hemophilia: Homozygous or
Heterozygous?
Only males affected
 Not Y-linked
 Skips a generation: recessive
 X-linked
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Try It!
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Let us begin by drawing the pedigree described
below (which is not necessarily an autosomal
dominant condition and which contains
extraneous information).
The Scenario
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Alice and Bob have a two year old son, Charles, who is
showing mental retardation, short stature, micropenis,
and cryptorchidism. Alice has two living, unaffected,
brothers but her eldest brother died at age 9 and a
second brother died aged 10 months. Both had similar
problems to Charles. Alice's father, David, who was
symptomless, has a sister, Ethel, who has an unaffected
boy and girl, and a brother, Fred, who also has two
unaffected children. Alice's mother, Gertrude, has two
living sisters and had a brother who had died in
childhood and who, she remembers, had been mentally
retarded. Bob has two brothers, Henry and Ignatius,
who are still unmarried. His parents, John and Kate,
had tragic lives, both were adopted and never knew
their biological parents and both died as the result of a
road accident.
Step 1
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Begin with Alice, Bob
and Charles.
Here are three possible
drawings of this nuclear
family.
Correct Solution
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Alice and Bob are connected by a horizontal line
to show that this is a mating. Charles is
connected to that horizontal line to show that he
is a product of that mating.
Step 2
•Now add Alice's
siblings and parents to
the pedigree.
Choose One…
Correct Solution was Possiblilty 3
Alice and her four brothers are
connected vertically to a
horizontal line which is, in turn,
connected to the line drawn
between her parents David and
Gertrude. Her two dead brothers
(whom we presume died of the
same genetic disease - though
this can sometimes be a foolish
assumption without medical
evidence) are shaded in (to show
that they suffered from the
disease) and are crossed through
(to show that they are dead).
Step 3
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Now add Gertrude's siblings to the pedigree.
And David's siblings and his nephews and nieces
Finally add Bob's side of the family
Try Drawing it!!!
Correct Drawing!