Download Mendelian Genetics

Mendelian Genetics
Pre-Mendel Theory
• Blending theory
– A permanent blend of each parent
– Blend of hereditary material inseparable from that
point forward
• Problems
– If blending is true, then individuals will reach a
uniform appearance
– Some inheritable traits skip generations and reappear
in the next generation.
Particulate Theory
• Parents transmit to their offspring discrete
inheritable factors (genes) that remain separate
factors from one generation to the next.
• Mendel influenced by:
– Doppler (physicist): quantitative experimental
approach to study of natural phenomena
– Unger (botanist): interested Mendel in inheritable
variations in plants
Mendel’s peas
and methods
Genetics terms review
• Character = inheritable feature
• Trait = variant of an inheritable feature
• True-breeding = always same traits in offspring as
parents when parents are self-fertilized
• P, F1, F2 generations (progeny)
• Three generations of crosses reveal:
– Law of segregation
– Law of independent assortment
Law of dominance
revealed
(Dominant:recessive)
Alleles = alternative variations of same gene
• Each locus represented twice in diploid organisms:
- equal homologous loci as in true-breeding organisms or two
different alleles as in hybrids
Law of Segregation
2 classes
Punnett square
More helpful
vocabulary
Testcross = breeding
of unknown genotype
with homozygous
recessive
Law of independent assortment
Independence of alleles
occurs during metaphase I
when chromosomes are
separated
Segregation and assortment reflect
Laws of Probability
• Probability scale ranges from:
– 1 = event certain to occur
– 0 = event certain not to occur
• Random events are independent of
one another
– Rule of multiplication = probability
that independent events will occur
simultaneously is product of
individual probabilities. (e.g.
probability of two hybrids producing a
homozygous recessive offspring)
– Rule of addition = probability of an
event that can occur in two or more
independent ways is the sum of the
separate probabilities of the different
ways. (e.g. probability of being a
heterozygote)
Using probability in solving genetic problems
• Trihybrid cross: what is probability that two
organisms of AaBbCc will produce an offspring
with aabbcc?
– Treat as 3 monohybrid crosses
• Aa x Aa: probability of aa = 1/4
• Bb x Bb: probability of bb = 1/4
• Cc x Cc: probability of cc = 1/4
– Simultaneous probability for these individual
probabilties = 1/4 x 1/4 x 1/4 = 1/64
Another trihybrid question
Character
Flower color
Seed color
Seed shape
Trait & Genotype
Purple: PP. Pp
White: pp
Yellow: YY, Yy
Green: yy
Round: RR, Rr
Wrinkled: rr
• If PpYyRr x Ppyyrr, what are chances that
offspring will show at recessive phenotypes for at
least two of the three traits?
Character
Flower color
Seed color
Seed shape
Trait & Genotype
Purple: PP. Pp
White: pp
Yellow: YY, Yy
Green: yy
Round: RR, Rr
Wrinkled: rr
Known genotypes which meet conditions
ppyyRr
1/4 x 1/2 x 1/2
ppYyrr
1/4 x 1/2 x 1/2
Ppyyrr
1/2 x 1/2 x 1/2
PPyyrr
1/4 x 1/2 x 1/2
ppyyrr
1/4 x 1/2 x 1/2
PpYyRr x Ppyyrr
=
=
=
=
=
Probability
1/16
1/16
2/16
1/16
1/16
6/16 or
3/8 chance
of two recessive
traits
Using probabilities as predictors
• Punnett square results or probability expressions
do not guarantee that a F2 flower from a
monohybrid cross will grow out to be white (pp),
only that there is a 1/4 chance.
• In a large sample, there will be a 25% chance of
white flowers
• The larger the sample size, the closer the results
will conform to predictions.
Other patterns of
inheritance
• Incomplete
dominance produces
an intermediate
phenotype between
dominance and
recessiveness
• Segregation and
independent
assortment still
apply
Relationships between alleles
• Dominance/recessiveness vary along a continuum
Complete dominance
(A is dominant)
AA and Aa have the
same phenotype
Incomplete dominance
(A is incompletely
dominant)
Aa = Intermediate
phenotype between
two homozygotes:
AA and aa
Codominance
(no dominance)
Aa = Both alleles
are equally
expressed in
phenotype
Levels of gene expression
• Codominance: MN blood groups
– Blood Type
–
M
–
N
–
MN
Genotype
MM
NN
MN
• MN blood type expresses both M and N glycoproteins on red
blood cell surface
Tay-Sachs Disease
• Recessively-inherited disorder (requires both recessive
alleles)
– One of several “storage disorders”: lipids accumulate in brain
because dysfunctional enzymes are produced by recessive genes
• Organismal level: heterozygotes are symptom-free
– Appears that dominant allele is completely dominant
• Biochemical level: intermediate enzyme level occurs half-way
between no activity and complete activity
– Seems to be a case of incomplete dominance
• Molecular level: heterozygotes produce equal quantities of normal
and dysfunctional enzymes; they don’t have disease because there
is sufficient normal activity to metabolize lipids in the brain.
Dominant/recessive relationships
• A consequence of mechanisms which determine
phenotype expression
• Are not a result of quantity of alleles in a
population; dominant alleles are not necessarily to
most abundant in the population
– Polydactyly (extra fingers/toes) is dominant, but only
occurs in 1 out of 400 births
Molecular basis of blood types
Multiple alleles
Codominant
alleles
Pleiotropy
• Ability of a single gene to have multiple
phenotypic effects
– Single defective gene gives rise to a complex set of
symptoms -- e.g. sickle-cell anemia
– Tigers and Siamese cats: gene for fur pigmentation
also influences connection between eyes and brain
• Defective gene causes abnormal pigmentation and cross-eye
condition
Epistasis
• Interaction between two nonallelic genes in which
one modifies the expression of the other
– If one gene suppresses expression of a 2nd gene then
the first gene is said to be epistatic to the 2nd gene
– A dihybrid cross involving epistasis will not yield the
typical 9:3:3:1 ratio
Rodent fur pigment genes
C = pigment deposition
is epistatic to:
B = melanin production
Black = dominant
Brown = recessive
Albino = no pigment
Polygenic inheritance
• Quantitative character which varies on a
continuum within a population
– Caused by additive effects of two or more genes
expressed in a single phenotype
• e.g. human skin coloration
– AABBCC = very dark skin
– aabbcc = very light skin
– AaBbCc = intermediate-colored skin
» AABbcc also expresses as intermediate since alleles are additive
• [summarized on next slide]
“Doses” of
pigmentation
Role of environment in expression
• Single genotype may have a range of phenotypes
called the norm of reaction for the genotype
– Hydrangea flowers, tanning of skin, blood cell count
(varies with altitude, activity, infection)
– Broadest norms occur with polygenic traits (including
behaviors)
– Himalayan rabbit fur pigmentation
Ice bag
Human genetics
• Pedigree: device used to
study humans
– Human generation time
about 20 years
– Experiments are impossible
– Must deduce genetics from
family histories
• Recall pedigree analysis
–
–
–
–
–
Squares =
Circles
=
Horizontal lines =
Vertical lines =
Filled symbol =
Recessively inherited disorders
• Defective allele usually codes for malfunctional protein
or no protein at all.
• Heterozygotes are usually phenotypically normal
– Can act as a carrier (transmit gene to next generation)
• Range in severity from nonlethal traits (albinism) to lethal
traits (cystic fibrosis)
• Not usually distributed equally among all racial groups -different genetic histories of world’s people
• 1/4 probability of disorder occurring from 2 heterozygote
parents (Aa x Aa); 2/3 probability that child will be a
heterozygote (carrier)
• Increased chance of inheriting recessive disorders if
parents are closely related -- consanguinity; most cultures
have laws to prevent this.
Cystic fibrosis
• 1/2,500 Caucasians (rarer in other races); most
common lethal disorder in U.S.
• 4% of Caucasians are carriers
• Caused by defective (or absent) chloride channel
proteins in membranes of lungs, pancreas, and
intestines; allows accumulation of extra thick
mucous -- favors bacterial infections
• To clear lungs person must be “pounded”
regularly to loosen mucous clots
Tay sachs
• 1/3,600 births; 100X higher incidence in
Ashkenazic (central European) Jews than among
Sephardic (Mediterranean) Jews and non-Jews.
• Lipid accumulation in brain; death after few years
• Heterozygotes function normally with half of
normal enzyme present
Sickle-cell disease
• 1/400 African Americans in US;
• Single amino acid substitution in hemoglobin
due to point mutation
• Normal hemoglobin gene = A
• Sickled hemoglobin gene = S
– AS = mild disorder; resistance to malaria (important in equatorial regions of
Africa); sickle-cell trait
– SS = sickle-cell disease; Hb crystallizes under acidic conditions (when
levels of CO2 rise during exercise); impaired circulation causes severe pains
in abdomen, back, head, and extremities; heart enlargement, atrophy of brain
cells (about 0.2% African Americans)
• Heterozygotes (carriers; 9% African Americans; 45% African blacks) have a
survival advantage and this tends to keep the sickle-cell gene present in the
population
• Pleiotropic inheritance is demonstrated in the multiple symptoms of the disorder
Phenylketonuria (PKU)
• Failure to metabolize amino acid phenylalanine;
phenylketones appear in urine (-uria)
• Results in poor brain development during infancy
– Severe mental retardation
– Rarely lives more than 30 years
• Sensitive to all foods containing phenylalanine
– These foods carry warning labels on them
• WARNING PHENYLKETONURICS: This product contains
phenylalanine
• When caught early in infancy, disorder can be treated
nutritionally and normal brain development occurs.
Adults are not as sensitive to phenylalanine as infants
because their brains are finished being developed.
• All newborns in US hospitals are screened for PKU
Dominantly inherited disorders
• Achondroplasia: type of dwarfism; affects
1/10,000 who are heterozygous (Aa); spontaneous
mutation in a normal parent’s gamete; 99.9% of
population is pure recessive (aa); pure dominant
(AA) embryos usually abort spontaneously
Late-acting lethal dominants
• Express too late in life to be eliminated -- children
already adults and produced own children
• Huntington’s disease: degeneration of nervous
system; appears between 35-40 years; irreversible
and lethal.
– Children of affected parents (Hh) have 50% chance of
developing the disorder in adulthood.
– New blood test can detect allele for the disorder before
symptoms appear; still not curable
Multifactorial disorders
• Disease has a genetic (predisposition) and
environmental component
–
–
–
–
–
Heart disease
Diabetes
Cancer
Alcoholism
Some mental illnesses
• Education helps people avoid environments and
behaviors which contribute to these disorders
Tests for carriers
• Tay-Sachs
• Cystic fibrosis
• Sickle-cell disease
• Information from tests should be combined with
help from genetics counselor (usually in hospitals)
to decide course of action
Fetal testing
Consumes time
Ultrasound and fetoscopy
(1% risk of bleeding/fetal death)
End