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Exceptions to the Rules
Ch. 14 and 15
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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
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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
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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
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Multiple alleles:
• more than 2 possible alleles for a gene. Ex: human blood types
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Pleiotropy:• genes with multiple
phenotypic effect.
• one gene affects more than one phenotypic character
• Ex: sickle-cell anemia
•Normal and sickle red blood cells
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Pleiotropy • Most genes are pleiotropic – one gene affects more than one phenotypic
character• 1 gene affects more than 1 trait• dwarfism (achondroplasia) • gigantism (acromegaly)
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Aa x aa
Inheritance pattern of Achondroplasia
a a
A
a
A a
A
a
Aa x Aa
Aa
aa aa
Aa
50% dwarf:50% normal or 1:1
AA
aa
Aa
67% dwarf:33% normal or 2:1
Aa
lethal
dominantinheritance
dwarf dwarf
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Epistasis
B_C_B_C_
bbC_bbC_
_ _cc_ _cc
• One gene completely masks another gene– coat color in mice = 2 separate genes• 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
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Epistasis in Labrador retrievers• 2 genes: (E,e) & (B,b)– pigment (E) or no pigment (e)– pigment concentration: black (B) to brown (b)
E–B–E–bbeeB–eebb
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Polygenic inheritance• Some phenotypes determined by additive
effects of 2 or more genes on a single character– phenotypes on a continuum– human traits• skin color• height• weight• intelligence• behaviors
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Pedigrees
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Examples of 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.
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Examples of 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.
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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
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Heterozygote crosses
Aa x Aa
A amale / sperm
A
afem
ale
/ eg
gs
AA
Aa aa
Aa
Aa
A
a
Aa
A
a
AA
Aa aa
Aa
• Heterozygotes as carriers of recessive alleles
carrier
carrier disease
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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
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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.
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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
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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
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Hemophilia
Hh x HHXHYXHXh
XHXh
XH
Xh
XHYY
XH
sex-linked recessive
XH Ymale / sperm
XH
Xh
fem
ale
/ eg
gs XHXH
XHXh
XHY
XhY
XHXH XHY
XHXh XhY
carrier disease
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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”
XH
Xh
XHXh
patches of black
patches of orange
tricolor catscan only befemale
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Human sex-linkage
• X-inactivation: 2nd X chromosome in females condenses into a Barr body (e.g., tortoiseshell gene gene in cats)
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2006-2007
Errors of MeiosisChromosomal Abnormalities
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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
n
n-1
n+1
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Alteration of chromosome number
all with incorrect number 1/2 with incorrect number
error in Meiosis 1
error in Meiosis 2
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trisomy2n+1
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
monosomy2n-1
n-1 n
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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
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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
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Sex chromosomes abnormalities• Human development more tolerant of wrong
numbers in sex chromosome• But produces a variety of distinct syndromes
in humans– XXY = Klinefelter’s syndrome male – XXX = Trisomy X female– XYY = Jacob’s syndrome male– XO = Turner syndrome female
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• 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
Klinefelter’s syndrome
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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
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Trisomy X• XXX– 1 in every 2000 live births– produces healthy females• Why?• Barr bodies
– all but one X chromosome is inactivated
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Turner syndrome• Monosomy X or X0– 1 in every 5000 births– varied degree of effects – webbed neck– short stature– sterile
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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
erro
r of
repl
icati
oner
ror o
fcr
ossi
ng o
ver
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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.
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Human disorders
• Testing:•amniocentesis•chorionic
villus sampling (CVS)• Examination of the fetus
with ultrasound is another helpful technique
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Pre-Implantation Genetic Diagnosis (PGD)
Removing a cell for diagnosis from a human embryo.
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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• albinism• cystic fibrosis• Tay sachs• sickle cell anemia• PKU
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PRACTICE
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Chicken Feathers- A black chicken crossed with a white rooster has offspring with
black and white feathers.
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Karyotype Practice
1 2 3 4 5
6 7 8 9 10
11 12 13 14 15
16 17 18 19 20
21 22 23
Down Syndrome Male
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Karyotype Practice
Klinefelter Male
1 2 3 4 5
6 7 8 9 10
11 12 13 14 15
16 17 18 19 20
21 22 23
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Karyotype Practice
Turner Syndrome Female
1 2 3 4 5
6 7 8 9 10
11 12 13 14 15
16 17 18 19 20
21 22 23
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Karyotype Practice
XYY Syndrome Male
1 2 3 4 5
6 7 8 9 10
11 12 13 14 15
16 17 18 19 20
21 22 23