Transcript Human Genetics and Pedigrees

Incomplete Vs. Co-dominance
• Codominance - A form of inheritance in which
both alleles are equally shown.
• Incomplete dominance - A form of inheritance
in which the heterozygous alleles are both
expressed, resulting in a combined
phenotype.
– Most commonly found in plants.
• A red and a white allele gives pink. If it were
codominance, you would see the red and
white colors.
Test Cross
• Used to determine an organisms genotype.
– Either Bb or BB
• Always a dominant unknown mated with pure
recessive
– B? X bb
Human Genetics: Karyotypes
46 TOTAL
46 TOTAL
Chromosomes
23
homologous
pairs
23
homologous
pairs
What is the difference between an Autosome
and a Sex-chromosome?
• Autosomes are the first 22
homologous pairs of human
chromosomes that do not
influence the sex of an
individual.
• Sex Chromosomes are the 23rd
pair of chromosomes that
determine the sex of an
individual.
Autosomal Traits
• Genes located on Autosomes control
Autosomal traits and disorders.
2 Types of Traits:
• Autosomal Dominant
• Autosomal Recessive
Autosomal Recessive Traits
• In order to express the trait, two recessive alleles
must be present.
• What would be the genotype of an individual with an
autosomal recessive trait? (A = dominant)
– aa
• What would be the genotype of an individual
without the autosomal recessive trait?
– AA or Aa
– Aa – called a Carrier because they carry the
recessive allele and can pass it on to offspring, but
they do not express the trait.
Albinism
Defect of melanin production that results in little or
no color in the skin, hair, and eyes
Albinism
Albinism
How does
it
happen?
Affected
Genotype:
aa
Cystic Fibrosis
Disease that causes the
body to produce unusually
thick, sticky mucus that:
•Clogs the lungs and leads
to lung infections
• Obstructs the pancreas
• Stops natural enzymes
from helping the body
break down and absorb
food
How does
it
happen?
Affected
Genotype:
cc
Sickle Cell Anemia
Caused by an abnormal
hemoglobin shape which
causes the red blood
cells to have a crescent
shape.
Red blood cells carry oxygen.
How does
it
happen?
Affected
Genotype:
ss
Tay–Sachs disease
• Symptoms:
– a build up of lipids in the brain
– Seizures
– blindness
• Mainly occurs in Jewish people
Tay-Sachs Disease
PKU (phenylketournia)
• symptoms;
– cannot break down the specific amino acid
(phenylalanine found in foods like milk)
– results in brain damage
• Mainly occurs in people of European descent
Autosomal Dominant Traits
• If dominant allele is present on the autosome, then
the individual will express the trait.
• What would be the genotype of an individual with an
autosomal dominant trait?
– AA and Aa (Heterozygotes are affected)
• What would be the genotype of an individual
without the autosomal dominant trait?
– aa
Huntington’s Disease
Causes the break down of
brain cells, (neurons) in
certain areas of the brain.
Causes uncontrolled
movements, loss of
intellectual faculties, and
emotional disturbance.
How does
it
happen?
Affected
Genotype:
HH or Hh
Progeria
• Drastic premature aging, rare, die by age 13.
Symptoms include limited growth, alopecia,
small face and jaw, wrinkled skin,
atherosclerosis, and cardiovascular problems
but mental development not affected.
Sex-Linked Traits
• Sex-linked traits are produced by genes only on the X
chromosome.
– They can be Dominant or Recessive.
• What would be the genotypes of a male and female that have a
Sex-linked Dominant trait and do not express the trait?
• Expresses Trait:
Male - XA Y
Female - XA XA or XA Xa
• No Expression:
Male - Xa Y
Female - Xa Xa
• What would be the genotypes of a male and female that have a
Sex-linked Recessive trait and do not express the trait?
• Expresses Trait:
Male - Xa Y
Female - Xa Xa
• No Expression:
Male - XA Y
Female - XA XA or XA Xa
(Carrier)
• Most Sex-linked traits are Recessive!
Color Blindness
Inability to see colors in the normal way
How does it
happen?
Affected
Genotypes:
XbXb
XbY
Hemophilia
Inability of the blood to clot properly
How does it
happen?
Affected
Genotypes:
XhXh
XhY
Pedigree Analysis
• A pedigree shows the relationship between parents
and children over the generations and how a trait is
passed down from one generation to the next.
How to Construct a Pedigree?
• A Pedigree is a visual showing the pattern of
inheritance for a trait. (Family tree)
•
•
•
•
Symbols and Rules:
Male =
Female =
Affected =
Unaffected =
Carrier =
Link parents together with a line and then
make a vertical line to connect to offspring.
Autosomal Dominant Pedigree
• Draw a Pedigree showing a cross between
Heterozygous parents that have 2 boys and 2
girls. (Show all possibilities)
Genotypes of Affected and Unaffected:
• AA and Aa = Affected aa = Unaffected
Aa
aa
Aa
Aa
Aa
AA
Autosomal Recessive Pedigree
• Draw a Pedigree showing a cross between
Heterozygous parents that have 2 boys and 2
girls. (Show all possibilities)
Genotypes of Affected and Unaffected:
• AA=Unaffected Aa=Carrier, Unaffected
aa=Affected
Aa
aa
Aa
Aa
Aa
AA
Sex-Linked Recessive Pedigree
• Draw a Pedigree showing a cross between a normal
male and a Carrier Female.
• Genotypes of Parents:
• Male = Xh Y Female = XH Xh
XRY
XRY
XR
Xr
X rY
XRXR
XRXr
Characteristics of Autosomal Dominant, Autosomal
Recessive, and Sex-linked Recessive Traits
• In groups, analyze your notes on each type of
disorder and examine the pedigrees.
• Come up with rules/characteristics for each
type of Trait.
Types of Pedigrees: Recessive
Affected Genotypes: bb
Unaffected Genotypes: BB or Bb
HINT: Recessive Disorders skip
generations
Is the Pedigree below showing
Recessive Inheritance?
Recessive Inheritance?
Recessive Inheritance?
Types of Pedigrees: Sex-linked
Affected Genotypes:
XbXb or XbY
Unaffected Genotypes:
XBXB or XBXb and XBY
HINT: Mainly males are affected
Is the Pedigree below showing SexLinked Inheritance?
Sex-linked Inheritance?
Sex-linked Inheritance?
Types of Pedigrees: Dominant
Affected Genotypes: BB or Bb
Unaffected Genotypes: bb
Is the Pedigree below showing
Dominant Inheritance?
Dominant Inheritance?
Dominant Inheritance?
What
is genotype
of Individual IHow
many
generations?
What type of Inheritance?
1?
What
is genotype
of Individual IHow
many
generations?
What type of Inheritance?
1?
Pedigrees and Genetic Disorders
Mutations
Gene Mutations
1. Caused by a change in the amino acid sequence of a
protein
2. Impacts of mutations: lethal, neutral, or beneficial
3. Gene mutation are caused by a change to one or more
bases in nucleotide sequence of DNA
A. mutations are rare because cells have proofreading and correction
enzymes
B. these chance events (mutations) are caused by mutagens
Ex. viruses, UV light, chemicals like mustard gas
Mutations
Chromosomal Mutations
1. Caused by a change in structure or number of
chromosomes
2. Detected by KARYOTYPING which matches
homologous chromosomes in a diploid (2N) cell
by:
1. Size of chromosome
2. Length of chromatid arms
3. Centromere location
Karyotype
Karyotype of a normal
1
2
3
female
4
5
Karyotype of a normal
1
2
3
male
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Chromosomal Mutations
Theoretically Normal Chromos ome Structure
note : ea ch letter or seg men t o n a chro m oso me rep resen ts a gen e in pro per lo cus
A
B
C
D
E
F
and
G
H
I
J
K
Structure
a. Deletion - loss of part of a chromosome AC DEF
b. Duplication - segment is repeated ABBC DEF
c. Inversion - orientation is reverse of normal AED CBF
(twisting)
d. Translocation - parts are broken off and added to another
chromosome
Ex. ABC DEF and GH IJK is changed to ABC JK and GH IDEF
Chromosomal Mutations
Nondisjunction deals with whole chromosomes or sets
of chromosomes "not coming apart.”
During meiosis a cell gets both copies of a chromosome
and the other cell is missing one chromosome
because sister chromatids didn’t separate
I.
Monosomy is the condition of having only 1 chromosome of a
homologous pair
Turner Syndrome= monosomy of 23rd pair
II. Trisomy is the condition of having 3 chromosomes of a
homologous pair
Down syndrome (21st pair), Klinefelter Syndrome (23rd pair), XYY
syndrome (23rd pair)
Down Syndrome
Cystic fibrosis
• Caused by a recessive allele; ff
• Symptoms:
– organs produce a thick mucus causing congestion
in the lungs
– digestive tract problems
– pneumonia like symptoms
• Mainly occurs in Caucasians
Albinism
• Caused by a recessive allele; aa
• Symptoms:
– no melanin in the skin
• resulting in an albino:
– white skin
– pink to red eyes
Huntington disease
• Caused by a dominant allele; HH or Hh
• Symptoms:
– breaks down the nervous system, fatal
Sickle Cell Anemia
• Caused by a co-dominant allele (A’) which codes for
abnormal hemoglobin
– hemoglobin is found on the red blood cells and carries
oxygen
• Symptoms:
– sickle shape red blood cells, clotting, extensive pain, can
be fatal
• Genotypes:
– AA = normal
– AA’ = normal but a carrier
– A’A’ = diseased
• Mainly African people
Color blindness
• Sex-linked disorder caused by a recessive
allele only found on the X sex chromosome:
– XC XC = normal female; XC Xc= normal, but a carrier
– Xc Xc= color blind female
– XC Y = normal male; XcY = color blind male
• Symptoms:
– cannot distinguish red from green
Color Blindness
Hemophilia
• Sex-linked disorder caused a recessive allele
only found on the X sex chromosome
– normal female = XH XH= normal, but a carrier XH Xh
– hemophiliac female = XhXh
– normal male = XHY; XhY = hemophiliac male
• Symptoms:
– excessive bleeding from a minor injury, fatal
Down syndrome (trisomy)
• Cause by nondisjunction
– too many chromosomes: 3 chromosomes for the
21st pair of homologous chromosomes; resulting
in 47 total chromosomes
• Symptoms:
– Almond shape eyes
– Enlarged tongues
– Some can be mentally and physically challenged
Down syndrome (trisomy)
Klinefelter syndrome
• Cause by nondisjunction
– too many chromosomes: 3 sex chromosomes =
XXY; the sex is male; resulting in 47 total
chromosomes
• Symptoms:
– Underdeveloped male sex organs
– Sterility
– May have feminine body parts
Turner Syndrome
• Cause by nondisjunction
– not enough chromosomes; 1 sex chromosome =
XO the sex is female; resulting in 45 total
chromosomes
• Symptoms:
– Females are usually short
– Sex organs may not develop
– Sterility
Turner Syndrome
Pedigree Analysis
• In a pedigree chart, certain shapes indicate gender and colors signify
whether or not they carry the trait or show the trait
• A circle represents a female.
• A square represents a male.
• A horizontal line between 2 people indicates marriage.
• A vertical line extending from a marriage line indicates the offspring from
the couple.
• A solid shaded shape represents a person who shows the trait in their
phenotype.
• A half shaded shape represents a person who is a carrier of the trait but
does not show the trait. NOTE: some pedigrees don’t indicate carriers
Pedigree Analysis
Pedigree Analysis
Generations are indicated with Roman numerals (I, II, III) and
individuals within generations are marked with arabic
numbers (1, 2, 3, 4).
Pedigree Questions: this pedigree doesn’t indicate carriers
1. What sex is individual I-2?
2. How many children are in the 2nd generation
from the union of I-1 and I-2?
3. What are their sexes?
4. Which individual was married in generation 2?
5. How many daughters are in generation 3?
6. How many sons are in generation 4?
7. List the 3 individuals who were afflicted with
sickle cell anemia?
8. Were individuals I-1 and I-2 carriers of sickle cell?
9. How do you know? (Explain your answer to #8)
10. List another carrier of sickle cell anemia.
= sickle cell
anemia
Karyotype Practice
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Down Syndrome Male
Karyotype Practice
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Klinefelter Male
Karyotype Practice
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Turner Syndrome Female
Karyotype Practice
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XYY Syndrome Male
Unit 9, Part 4 Notes
Pedigrees and Genetic Disorders
• Definition: a graphic
representation of genetic
inheritance used by geneticists
to map genetic traits
Affected
What is a pedigree?
What does a pedigree
look like?
• Generations in separate
rows indicated by Roman
numerals (I, II, III…)
• Individuals within one
generation indicated by
Arabic numerals (1, 2, 3…)
• Parents connected by
horizontal lines
• Offspring connected by
vertical lines
Dead
• Occurs in people of Jewish
descent
• Enzyme that breaks down
lipids in the brain is
defective. Lipid buildup
kills brain cells.
• Always results in death,
usually by age 5
• Caused by a recessive
allele
Let’s look at
an example…
Tay Sachs
disease
Pedigree for Tay Sachs disease
Carrier
Carrier
• Caused by a rare dominant
allele
• Doesn’t show up till age 3050
• Breaks down areas of the
brain, loss of control of all
body functions
• No treatment
Huntington’s
Disease
Pedigree for Huntington’s
Disease
normal
carrier
What if the trait is sex-linked?
How can you tell?
Answer: Most affected
individuals are males
Let’s try one…Is this sex-linked or not?
Answer: Yes
More practice
with pedigrees…
• Interactive pedigree
activity
• Pedigree quiz
• Punnett Square and
Pedigree problems
Sex Chromosomes
• 2 sex chromosomes
• Typical Female = XX
• Typical Male = XY
Autosomes
Autosomes:
Any
chromosome
that’s not a sex
chromosome
•44 Autosomes
•22 pairs of
Autosomes
Autosomal Recessive Traits
• Heterozygotes are Carriers with a normal phenotype.
• Most affected children have normal parents. (Aa x Aa)
• Two affected parents will always produce an affected child.
(aa x aa)
• Two unaffected parents will not produce affected children
unless both are Carriers. (AA x AA, AA x Aa)
• Affected individuals with homozygous unaffected mates will
have unaffected children. (aa x AA)
• Close relatives who reproduce are more likely to have affected
children.
• Both males and females are affected with equal frequency.
• Pedigrees show both male and female carriers.
Examples of Autosomal Recessive Disorders
•
•
•
•
•
Congenital Deafness
Diabetes Mellitus
Sickle Cell anemia
Albinism
Phenylketoneuria (PKU) – Inability to break down
the amino acid phenylalanine. Requires
elimination of this amino acid from the diet or
results in serious mental retardation.
•
Galactosemia – enlarged liver, kidney failure,
brain and eye damage because can’t digest milk
sugar
Cystic Fibrosis – affects mucus and sweat glands,
thick mucus in lungs and digestive tract that
interferes with gas exchange, lethal.
Tay Sachs Disease – Nervous system destruction
due to lack of enzyme needed to break down
lipids necessary for normal brain function. Early
onset and common in Ashkenazi Jews; results in
blindness, seizures, paralysis, and early death.
•
•
Autosomal Dominant Traits
• Heterozygotes are affected
• Affected children usually have affected parents.
• Two affected parents can produce an unaffected
child. (Aa x Aa)
• Two unaffected parents will not produce affected
children. (aa x aa)
• Both males and females are affected with equal
frequency.
• Pedigrees show no Carriers.
Examples of Autosomal Dominant Disorders
•
•
•
•
Dwarfism
Polydactyly and Syndactyly
Hypertension
Hereditary Edema
•
Chronic Simple Glaucoma – Drainage system for fluid in the eye does not work and pressure
builds up, leading to damage of the optic nerve which can result in blindness.
Huntington’s Disease – Nervous system degeneration resulting in certain and early death.
Onset in middle age.
Neurofibromatosis – Benign tumors in skin or deeper
Familial Hypercholesterolemia – High blood cholesterol and propensity for heart disease
Progeria – Drastic premature aging, rare, die by age 13. Symptoms include limited growth,
alopecia, small face and jaw, wrinkled skin, atherosclerosis, and cardiovascular problems but
mental development not affected.
•
•
•
•
Examples of Sex-Linked Recessive Disorders
• Red/Green Colorblindness – Difficulty perceiving differences between
colors (red or green, blue or yellow).
• Hemophilia – Absence of one or more proteins necessary for normal
blood clotting.
• Deafness
• Cataracts – opacity in the lens that can lead to blindness
• Night blindness – (Nyctalopia) rods do not work so that can not see in the
dark
• Glaucoma – pressure in the eye that can lead to optic nerve damage and
blindness
• Duchenne Muscular Dystrophy – progressive weakness and degeneration
of skeletal muscles that control movement due to absence of dystrophin
(protein that maintains muscle integrity). Mainly in boys, onset 3-5 yrs, by
12 years can’t walk, and later needs respirator.
Sex-Linked Disorder
Linked to sex chromosomes
Recessive Disorders – caused
by recessive alleles
Sex-Linked Recessive Traits
• More males than females are affected.
• An affected son can have parents who have the
normal phenotype. (XAY x XAXa)
• For a daughter to have the trait, her father must also
have it. Her mother must have it or be a carrier.
(XaY, XaXa, XAXa)
• The trait often skips a generation from the
grandfather to the grandson.
• If a woman has the trait (XaXa), all of her sons will be
affected.
• Pedigrees show only female carriers but no male
carriers.
Genetic Counselor Activity
• Imagine that you are a Genetic
Counselor assigned to family to
discuss with them the possibility
of their child inheriting a genetic
disorder.
• You are given the family history and
whether or not the disorder is
Autosomal Dominant or Autosomal
Recessive.
• Draw Punnett Squares to determine
odds of children inheriting the disease
and answer the questions on the
worksheet.
What is a Pedigree???
Diagram showing a family tree and patterns of
inheritance.