Transcript Exceptions to the Rules

Exceptions to the Rules
Ch. 14 and 15
Extending Mendelian genetics
• Mendel worked with a simple system
– peas are genetically simple
– most traits are controlled by a single gene
– each gene has only 2 alleles, 1 of which
is completely dominant to the other
• The relationship between
genotype & phenotype
is rarely that simple
Incomplete dominance
• appearance between
the phenotypes of the 2
parents. Ex: carnations
• Heterozygote
shows an
intermediate,
blended
phenotype
– example:
• RR = red flowers
• rr = white flowers
• Rr = pink flowers
– make 50% less
color
•Incomplete dominance in carnations:
red, pink, white
Co-dominance
• 2 alleles affect the phenotype equally &
separately
– not blended phenotype
– human ABO blood groups
– 3 alleles
• IA, IB, i
• IA & IB alleles are co-dominant
– glycoprotein antigens on RBC
– IAIB = both antigens are produced
• i allele recessive to both
Multiple alleles:
• more than 2 possible alleles for a gene.
human blood types
Ex:
Pleiotropy:
•
genes with multiple
phenotypic effect.
• one gene affects
more than one
phenotypic
character
• Ex: sickle-cell
anemia
•Normal and sickle red blood cells
Pleiotropy
• Most genes are pleiotropic
– one gene affects more than one phenotypic
character
• 1 gene affects more than 1 trait
• dwarfism (achondroplasia)
• gigantism (acromegaly)
Inheritance pattern of Achondroplasia
Aa x aa
Aa x Aa
dominant
inheritance
A
a
a
Aa
Aa
dwarf
a
aa
A
dwarf
aa
50% dwarf:50% normal or 1:1
A
a
AA
Aa
lethal
a
Aa
aa
67% dwarf:33% normal or 2:1
Epistasis
• One gene completely masks another gene
– coat color in mice = 2 separate genes
B_C_
bbC_
_ _cc
• C,c:
pigment (C) or
no pigment (c)
• B,b:
more pigment (black=B)
or less (brown=b)
• cc = albino,
no matter B allele
• 9:3:3:1 becomes 9:3:4
Epistasis in Labrador retrievers
• 2 genes: (E,e) & (B,b)
– pigment (E) or no pigment (e)
– pigment concentration: black (B) to brown (b)
eebb
eeB–
E–bb
E–B–
Polygenic inheritance
• Some phenotypes determined by additive
effects of 2 or more genes on a single
character
– phenotypes on a continuum
– human traits
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skin color
height
weight
intelligence
behaviors
Pedigrees
Examples of Dominant Disorders
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Dwarfism
Polydactyly and Syndactyly
Hypertension
Hereditary Edema
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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.
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Examples of Recessive Disorders
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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.
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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.
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Recessive diseases
• The diseases are recessive because the allele
codes for either a malfunctioning protein or
no protein at all
– Heterozygotes (Aa)
• carriers
• have a normal phenotype because one “normal” allele
produces enough of the required protein
Heterozygote crosses
• Heterozygotes as carriers of recessive alleles
Aa x Aa
A
female / eggs
male / sperm
A
a
A
a
AA
AA
Aa
Aa
Aa
a
carrier
Aa
Aa
aa
carrier
disease
A
Aa
a
Genetic recombination
• Crossing over Genes that DO
NOT assort independently of each
other
• Genetic maps The further apart
2 genes are, the higher the
probability that a crossover will
occur between them and
therefore the higher the
recombination frequency
• Linkage maps Genetic map
based on recombination
frequencies
Karyotypes
• Maps of
chromosomes
• 22 homologous pairs
of human
chromosomes
• Sex Chromosomes are
the 23rd pair of
chromosomes that
determine the sex of
an individual.
Genes on sex chromosomes
• Y chromosome
– few genes other than SRY
• sex-determining region
• master regulator for maleness
• turns on genes for production of male hormones
– many effects = pleiotropy!
• X chromosome
– other genes/traits beyond sex determination
• mutations:
– hemophilia
– Duchenne muscular dystrophy
– color-blindness
Human sex-linkage
• SRY gene: gene on Y chromosome that triggers the development of
testes
• Fathers= pass X-linked alleles to all daughters only (but not to sons)
• Mothers= pass X-linked alleles to both sons & daughters
• Sex-Linked Disorders: Color-blindness; Duchenne muscular
dystropy (MD); hemophilia
sex-linked recessive
Hemophilia
XHHh
Xh x HH
XHY
XH
female / eggs
male / sperm
XH
XH
Y
XHXH
XHY
XHXh
Xh
XH
Xh
XHXh
carrier
Xh Y
disease
XHY
Y
X-inactivation
• Female mammals inherit 2 X chromosomes
– one X becomes inactivated during embryonic
development
• condenses into compact object = Barr body
• which X becomes Barr body is random
– patchwork trait = “mosaic”
patches of black
XH
XHXh
tricolor cats
can only be
female
Xh
patches of orange
Human sex-linkage
• X-inactivation: 2nd X chromosome in females condenses
into a Barr body (e.g., tortoiseshell gene gene in cats)
Errors of Meiosis
Chromosomal Abnormalities
2006-2007
Nondisjunction
• Problems with meiotic spindle cause errors in daughter
cells
– homologous chromosomes do not separate properly during
Meiosis 1
– sister chromatids fail to separate during Meiosis 2
– too many or too few chromosomes
2n
n-1
n
n+1
n
Alteration of chromosome number
error in Meiosis 1
error in Meiosis 2
all with incorrect number
1/2 with incorrect number
Nondisjunction
• Baby has wrong chromosome number~
aneuploidy
– trisomy
• cells have 3 copies of a chromosome
– monosomy
• cells have only 1 copy of a chromosome
n+1
n-1
n
n
trisomy
monosomy
2n+1
2n-1
Human chromosome disorders
• High frequency in humans
– most embryos are spontaneously aborted
– alterations are too disastrous
– developmental problems result from biochemical imbalance
• imbalance in regulatory molecules?
– hormones?
– transcription factors?
• Certain conditions are tolerated
– upset the balance less = survivable
– but characteristic set of symptoms = syndrome
Down syndrome
• Trisomy 21
– 3 copies of chromosome 21
– 1 in 700 children born in U.S.
• Chromosome 21 is the
smallest human chromosome
– but still severe effects
• Frequency of Down
syndrome correlates
with the age of the mother
Sex chromosomes abnormalities
• Human development more tolerant of wrong
numbers in sex chromosome
• But produces a variety of distinct syndromes
in humans
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XXY = Klinefelter’s syndrome male
XXX = Trisomy X female
XYY = Jacob’s syndrome male
XO = Turner syndrome female
Klinefelter’s syndrome
• XXY male
– one in every 2000 live births
– have male sex organs, but are
sterile
– feminine characteristics
• some breast development
• lack of facial hair
– tall
– normal intelligence
Jacob’s syndrome male
• XYY Males
– 1 in 1000 live male
births
– extra Y chromosome
– slightly taller than
average
– more active
– normal intelligence, slight learning disabilities
– delayed emotional maturity
– normal sexual development
Trisomy X
• XXX
– 1 in every 2000 live births
– produces healthy females
• Why?
• Barr bodies
– all but one X chromosome is inactivated
Turner syndrome
• Monosomy X or X0
– 1 in every 5000 births
– varied degree of effects
– webbed neck
– short stature
– sterile
error of
crossing over
error of
replication
Changes in chromosome structure
• deletion
– loss of a chromosomal segment
• duplication
– repeat a segment
• inversion
– reverses a segment
• translocation
– move segment from one chromosome to
another
Genomic imprinting
• Def: a parental effect on
gene expression
• Identical alleles may have
different effects on
offspring, depending on
whether they arrive in the
zygote via the ovum or via
the sperm.
Human disorders
• Testing:
•amniocentesis
•chorionic villus
sampling (CVS)
• Examination of the fetus
with ultrasound is another
helpful technique
Pre-Implantation Genetic Diagnosis (PGD)
Removing a cell for
diagnosis from a human
embryo.
Genetic counseling
• Genetics and pedigrees can help us
understand the past & predict the future
• Thousands of genetic disorders are inherited
as simple recessive traits
– from benign conditions to deadly diseases
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albinism
cystic fibrosis
Tay sachs
sickle cell anemia
PKU
PRACTICE
Wavy hair—a person that
is homozygous dominant
has curly hair. Homozygous
recessive genotype has
straight hair. A person who
is heterozygous has wavy
hair.
Red-green colorblindness—the gene that codes for
colorblindness is located on the x chromosome and is
inherited at the same time as the x chromosome.
Females are in luck because the gene is recessive.
Females need two copies of the gene to be
colorblind. Males only get one copy of the x
chromosome so if they get one copy of the gene they
are colorblind.
PKU—there are several alleles involved in coding for
enzyme that breaks down phenylalanine.
Phenylketonuria (PKU) is a disease in which the one
of the alleles is mutated so a person cannot
metabolize phenylalanine. The phenylalanine can
build up in the person’s brain cells causing severe
damage.
Skin color—the number of genes
that contribute to skin color in
humans is still being studied.
There are definitely more than
four genes that contribute to skin
color.
Cystic Fibrosis—this is a disease caused by
one of several hundred alleles within the
population. The phenotypes from this
disease range widely from susceptibility of
bronchitis to sterility.
Eye Color—the general eye color in
humans is determined by two different
genes. The eye color can also be affected
by several other genes.
Tay-Sacs Disease—the normal human has homozygous alleles for
producing LDL receptors. The LDL receptors help lower
cholesterol. The homozygous genotype for not producing LDL
receptors would not be able to survive. The heterozygous
genotype referred to as Tay-Sacs
Disease) has one allele
that produces LDL
receptors and one
allele that does not.
A person with this
genotype has about
half the LDL receptors
of a normal person
which can lead to high
cholesterol levels.
Chicken Feathers- A black chicken crossed
with a white rooster has offspring with
black and white feathers.
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