1. List 4 components of Mendel's hypothesis that led him to deduce the Law of Segregation
2. Distinguish between genotype and phenotype, heterozygous and homozygous, and dominant and recessive
3. State the Law of Independent Assortment
4. Distinguish between parental and recombinant phenotypes
5. Explain why a recessive sex-linked gene is always expressed in human males
MENDEL'S PRINCIPLES OF INHERITANCE
LAW OF SEGREGATION--The two genes that determine a particular trait separate
during the formation of gametes (gametes carry only one gene per trait)
. LAW OF DOMINANCE--when an individual possesses both alleles or a given trait (Aa),
the allele which is expressed is called DOMINANT and the allele which is masked
is called RECESSIVE. (recessive traits are expressed if -aa- or XaY)
LAW OF INDEPENDENT ASSORTMENT--Homologous chromosomes separate independently
from each other during the formation of gametes; therefore genes on different
chromosomes separate independently. (exception: linked genes).
PROBABILITY
the number of times an even is expected to happen /the number of opportunities
for it
to happen or number of trials
PRODUCT RULE-- the probability of two independent events occurring
simultaneously is the PRODUCT of their respective probabilities
SUM RULE -- the probability of EITHER one OR the other of two mutually exclusive
events occurring is the sum of their individual probabilities.
.
LARGE NUMBER RULE---probabilities are evident when observed in a large number of
occurrences or events. The larger the sample, the closer to the predicted
probability.
CHANCE HAS NO MEMORY!
Genetics
•Gene - unit of heredity.
•Genetics - the science of heredity (genes).
•Term coined at beginning of twentieth century (replaced previous studies of
“generation”, “inheritance”, “heredity”).
•In 1920’s classical genetics was often referred to as “Mendeliasm” and was a
relatively new (and controversial) area of biology.
•By 1950’s genetics recognized as unifying principle at core of the life
sciences.
Why study genetics?
•Understanding genetic processes is fundamental to comprehension of life itself.
Genetic function - cellular function, external appearance, linkage between
generations.
•Modern society depends on genetics. Breeding programs led to crops, livestock.
Biotechnology produces drugs, etc. Forensic science relies on DNA
identification.
•Genetics is a key component in medicine. Estimated at least 30% of pediatric
hospital admissions have direct genetic component.
Before Mendel
•Plant and animal breeding part of human history.
•Between 8000-1000 B.C., domestication of horses, camels, oxen, dogs.
•Primitive cereal plants (e.g. maize, wheat, rice) thought to have been
developed ~5000 B.C.
•Early attempts of human manipulation of heredity, awareness of genetic traits?
Greek thinking
•In Golden Age of Greek Culture, attention given to study of reproduction,
heredity.
•Hippocrates argued that both parents contributed traits to offspring, while
Aristotle believed that the male provided the form for the embryo, while the
female provided matter only, serving as an incubator.
The Dawn of Modern Biology (1600-1850)
•Preformation - Sex cells contain miniature adult homunculus.
•Theory of pangenesis - Darwin advocated idea of “gemmules” - units representing
each body part, gathered by blood into semen.
•Theory of epigenesis - an organism is derived from substances present in the
egg which must first be assembled and which differentiate during embryonic
development.
Blending inheritance
•As Mendel began his work, the idea of blending inheritance was popular.
•Idea put forward to account for fact that offspring show characteristics
similar to both parents.
.. In the mid-1800s, a monk named Gregor Mendel, working in Brno in the Czech
Republic, carried out an amazing piece of scientific detective work. Mendel
observed that the offspring of certain plants had physical characteristics
similar to the physical characteristics of the plants' parents or ancestors.
Gregor Mendel wondered why related organisms, both plant and animal, tended to
resemble one another and how familial resemblances might be explained.
.. Gregor Mendel reasoned that close observation of inheritance might provide
him with the answer for which he searched. He therefore set out to examine and
quantify the physical traits in pea plants (because of their speedy reproductive
cycles) in an attempt to predict the traits that would occur in future
generations.
During years of painstaking work, Mendel counted many thousands of instances of
seven different traits, including plant height, flower color and position, seed
color and shape, and pod color and shape.
.. Mendel concluded that certain particles or "factors" were being transmitted
from parent to offspring and so on, thus providing a connection from one
generation to the next. Mendel suggested that these factors were directly
responsible for physical traits. His interpretation of the experimental data
further suggested that each individual had not one, but two factors for each
trait, and that these factors interacted to produce the final physical
characteristics of the individual. Both the location and the identity of
Mendel's factors remained unknown for years .
.. Mendel suspected that heredity depends on contributions from both parents,
and that specific characteristics from each parent are passed on rather than
being blended together in the offspring.
Character, trait
•Character = heritable feature, a specific property of an organism.
– E.g. Flower colour
•Trait = each variant for a character.
– E.g. White flower
•Each pair of Mendel’s plant lines demonstrated a character difference.
Pea breeding
•Peas can be self-pollinated or cross-pollinated.
•Self-pollination - pollen from plant’s male organs (stamens) fertilizes same
plant’s female organs (carpel). Usual event in nature.
•Cross-pollination - fertilization between different plants. Must remove
immature stamens from plant (emasculation), apply pollen from another plant.
•Mendel used pure lines (true-breeding) - i.e. when self-fertilized, progeny
showed same trait as parent.
Pea as experimental organism
•Peas also:
– Cheap
– Easy to obtain
– Take up little space
– Have relatively short generation time
– Produce many offspring
Punnet square
•Device for predicting result of genetic cross.
•Conventions: Use capital letter for dominant allele, lower-case for recessive.
– E.g. Yellow vs. green pea:
• YY, Yy = yellow
• yy = green
Mendel’s experiments
•Typical experiment involved genetic cross.
– E.g. Mate plant bearning purple flowers with one having white flowers.
•Hybridization - mating of 2 pure lines.
•Parents = P (parental) generation.
•Hybrid offspring = F1 (first filial) generation.
•Progeny of self-pollinated F1 plants = F2 (second filial) generation.
•Mendel followed experiments across at least 3 generations: P, F1, F2.
Reciprocal crosses
•Phenotype = (Greek: “the form that is shown”)
– The physical and physiological traits of an organism.
•Mendel performed reciprocal crosses.
Blending vs. particulate inheritance
•If blending model of inheritance correct, a cross of purple-flowered plants and
plants with white flowers should yield progeny with in-between colour (Pale
purple?).
•Instead, F1 generation all had purple flowers!
•White flowers appeared in F2 generation - i.e. white flower contribution was
not lost.
Quantitative experimentation
•Note: Mendel counted the numbers of plants with each phenotype.
•Such procedure rarely (if ever!) used in inheritance studies prior to Mendel’s
work.
•Mendel was painstaking in his observations, and counted large numbers of
samples.
•Results:
F2 generation: 705 purple flower plants; 224 white flower plants. Ratio of 3.1:1
(almost 3:1).
Why didn’t F1 show white flowers?
•Mendel coined terms: dominant, recessive.
•Purple flowers are a dominant trait.
•White flowers are a recessive trait.
•The F1 generation of a cross between pure lines shows which phenotype is
dominant.
Next generation
•Mendel also selfed some F2 plants.
•166 yellow F2 plants yielded yellow peas only, 353 yellow F2 plants had mixture
of yellow & green peas (in 3:1 ratio).
•Selfed green F2 peas only bore green peas!
Mendel deduced …
•There are hereditary determinants of a particulate nature. (We use “gene” to
refer to these determinants.) Alternative versions of genes (different alleles)
account for variations in inherited characters.
•Each adult pea plant has 2 genes (gene pair) for each character studied. For
each character, an organism inherits 2 alleles, one from each parent.
Deductions …
•If the two alleles differ, the dominant allele is fully expressed in the
organism’s appearance while the recessive allele has no noticeable effect.
•Members of the gene pairs (alleles) segregate (separate) equally in the
gametes.
•Union of parental gametes is random.
Mendel’s “Laws”
•Mendel’s First Law:
– The two members of a gene pair segregate from each other into the gametes, so
that half the gametes carry one member of the pair, and the other half of
gametes carry the other member of the pair.
Punnet square
•Device for predicting result of genetic cross.
•Conventions: Use capital letter for dominant allele, lower-case for recessive.
– E.g. Yellow vs. green pea:
• YY, Yy = yellow
• yy = green
Terms
•Homozygous - organism with a pair of identical alleles for a character. E.g. a
pea plant with 2 alleles for white flowers is homozygous for the recessive
flower colour (pp); a purple one carrying both dominant alleles (PP) is
homozygous for the dominant flower colour.
•Heterozygous - organism having 2 different alleles for a character. E.g. Purple
flower plants of genotype Pp.
Terms
•Phenotype - organism’s physical and physiological traits.
•Genotype - organism’s genetic makeup.
Plants of different genotypes PP and Pp display same phenotype (purple flowers).
Mendel’s “Laws”
•Mendel’s Second Law:
– During gamete formation, the segregation of the alleles of one gene is
independent of the segregation of the alleles of another gene. *
Extending Mendelian genetics
•Characters Mendel studied in peas almost deceptively simple and
straight-forward.
•The relationship between genotype and phenotype may be more complex in many
traits.
Incomplete dominance
•Pea flowers in Mendel’s experiments were always one of two colours (purple or
white).
•Some flowers, like carnations and snapdragons have three different
possibilities: red, white, and pink.
•Snapdragons display incomplete dominance in flower colour.
•Incomplete dominance - F1 hybrids display intermediate phenotype.
Mendel’s laws still apply
•Pink colour results from heterozygotes having less pigment than red parent,
more pigment than white parent.
•Segregation of alleles for snapdragon flower colour demonstrates particulate
inheritance is still occurring.
Codominance
•Complete dominance - phenotype of heterozygote and dominant homozygote are
indistinguishable. (E.g. Pea flower colour, pea seed shape, etc.)
•Codominance - 2 alleles affect phenotype in separate and distinguishable ways.
Codominance example
Review of dominance types
Dominance - One allele (dominant) dictates the phenotype, while the other allele
(recessive) contributes nothing to the phenotype.
Incomplete dominance - The two alleles are equally expressed but they together
produce an intermediate phenotype.
Codominance - The two alleles are equally expressed and each produces its own
phenotype.
Dominance/recessiveness relationships
• Range from complete dominance through various degrees of incomplete dominance,
to codominance.
• Reflect the mechanisms by which specific alleles are expressed in the
phenotype and do not involve the ability of one allele to “subdue” another at
DNA level.
• Do not determine or correlate with relative abundance of alleles in a
population.
Mendel’s “Laws”
•Mendel’s Second Law:
– During gamete formation, the segregation of the alleles of one gene is
independent of the segregation of the alleles of another gene. *
Plants differing in 2 characters
•We talked about pure line breeding with one character.
– Resulting F1 is monohybrid (e.g. Aa).
– Monohybrid cross - self-pollination of F1 heterozygotes to produce F2
(yielding 3:1 ratios for trait),
•Peas have several different characters, and Mendel also crossed lines that
differed in 2 characters.
– F1 is dihybrid (e.g. AaBb)
– Dihybrid crosses - self pollination of dihybrid F1 plants.
Mendel’s “Laws”
•Mendel’s Second Law:
– During gamete formation, the segregation of the alleles of one gene is
independent of the segregation of the alleles of another gene. *
Probability
•Mendel’s laws reflect same rules of probability as seen with tossing a coin, or
throwing dice.
•Probability scale: 0 to 1.
1 = certain to occur.
0 = no likelihood of occurring.
•Tossing coin: 2 sides, chance of getting heads = 1/2, chance of tails = 1/2.
•Dice: 6 sides, chance of getting a given number is 1/6.
•All possibilities must add up to 1.
Independent events
•Outcome of a given coin toss or dice throw is not affected by previous results.
Each throw is independent.
•Mendel’s second law states the same thing, but for combinations of different
genes (in gametes).
Calculating genetic ratios
•Punnett squares are helpful for small numbers of characters … not feasible for
more complex predictions.
•Branch diagrams are easier.
Calculating genetic ratios - product rule
•Product rule = the probability of independent events occurring together is the
product of the probabilities of the individual events.
•E.g.
– Probability of getting a 4 when rolling dice = 1/6.
– Probability of getting a 4 when rolling 2 dice =
1/6 x 1/6 = 1/36.
Calculating genetic ratios - sum rule
•Sum rule = the probability of either of two mutually exclusive events occurring
is the sum of the probabilities of the individual events.
•E.g.
– Probability of rolling two 4’s OR two 5’s?
– p (two 4’s) = 1/36; p (two 5’s) = 1/36.
1/36 + 1/36 = 1/18
Rule of thumb
AND Þ Multiply
OR Þ Add
Example
•Trihybrid, heterozygous for flower colour, seed colour, seed shape, crossed
with plant heterozygous for flower colour, homozygous recessive for seed colour
and shape.
P = PpYyRr x Ppyyrr
Incomplete dominance vs. codominance
•Heterozygote displays an intermediate phenotype.
– Usually uniform.
– If you didn’t know about the homozygous phenotypes, you might not know 2
alleles at work.
•Heterozygote displays a phenotype expressing both alleles distinctly.
– Generally NOT uniform.
– Traits from both parents can be seen.
Not black and white …
•Once you get down to a molecular level, what appeared to be incomplete
dominance may be revealed as codominance on a much smaller scale!
Problem-solving
•In sheep, lustrous fleece (L) results from an allele that is dominant over an
allele for normal fleece (l). A ewe (adult female) with lustrous fleece is mated
with a ram (adult male) with normal fleece. The ewe then gives birth to a single
lamb with normal fleece. From this single offspring, is it possible to determine
the genotypes of the two parents? If so, what are the genotypes? If not, why
not?
Answer
•We know the ewe must have at least one copy of L. The fact that she has
lustrous fleece means she could be homozygous (LL) or heterozygous(Ll).The ram
must be homozygous recessive (ll) to have normal fleece.
•The lamb does indicate the genotypes of the parents. The lamb must be genotype
ll, with one copy of l from the ram, and one from the ewe.
•Parent genotypes: Ewe: Ll; Ram: ll
Problem-solving
• How many different types of gametes can be formed by individuals of the
following genotypes? What are the possible gamete genotypes?
– AaBb
– AaBbCc
– AaBBcc
– AaBbcc
Answer
• AaBb - 4 possible combinations:
• 1/2 A x 1/2 B = 1/4 AB
• 1/2 a x 1/2 B = 1/4 aB
• 1/2 A x 1/2 b = 1/4 Ab
• 1/2 a x 1/2 b = 1/4 ab
Answer
• AaBbCc - 8 possible combinations:
• 1/2 A x 1/2 B x 1/2 C = 1/8 ABC
• 1/2 a x 1/2 B x 1/2 C = 1/8 aBC
• 1/2 A x 1/2 b x 1/2 C = 1/8 AbC
• 1/2 a x 1/2 b x 1/2 C = 1/8 abC
• 1/2 A x 1/2 B x 1/2 c = 1/8 ABc
• 1/2 a x 1/2 B x 1/2 c = 1/8 aBc
• 1/2 A x 1/2 b x 1/2 c = 1/8 Abc
• 1/2 a x 1/2 b x 1/2 c = 1/8 abc
Answer
• AaBBcc - 2 possible combinations:
• 1/2 A x 1 B x 1 c = 1/2 ABc
• 1/2 a x 1 B x 1 c = 1/2 aBc
• AaBbcc - 4 possible combinations:
• 1/2 A x 1/2 B x 1 c = 1/4 ABc
• 1/2 a x 1/2 B x 1 c = 1/4 aBc
• 1/2 A x 1/2 b x 1 c = 1/4 Abc
• 1/2 a x 1/2 b x 1 c = 1/4 abc
Problem-solving
• What are the possible genotypes resulting from a mating between individuals of
genotypes AaBbCc and AaBBcc? What frequencies are expected?
Answer
•First … look at each gene pair, and their probabilities of occurring from this
mating.
– E.g. Expect:
1/2 A x 1/2 A = 1/4 AA
1/2 A x 1/2 a = 1/4 Aa
1/2 a x 1/2 A = 1/4 Aa
1/2 a x 1/2 a = 1/4 aa
1 B x 1/2 B = 1/2 BB
1 B x 1/2 b = 1/2 Bb
1c x 1/2 C = 1/2 Cc
1c x 1/2 c = 1/2 cc
Branch diagram - use product rule
Mendelian genetics in humans
•Cannot do controlled crosses!
•In some cases, we can review records (matings, medical conditions in families).
•Pedigree analysis - Scrutiny of a family tree describing the occurrence of
heritable characters in parents and offspring across as many generations as
possible.
Tay-Sachs disease
•Remember from Chapter 7 - lysosomal disorder. Lethal condition - afflicted
children live a few years at most.
•Inherited as recessive allele. Heterozygotes (carriers) do not display
symptoms.
•In general population, frequency very rare, but higher incidence (~ 100 X)
amongst Ashkenazic Jews.
Problem-solving
•Patterns in pedigree analysis can give clues as to type of gene (dominant,
recessive) involved in a disorder.
•We know the probability of an affected person passing on genes to offspring in
either case.
•In autosomal recessive cases, unaffected parents can have affected child. This
is NOT seen with dominant genes.
Known conditions involving Mendelian inheritance
•Huntington’s disease (late-onset, autosomal dominant).
•Some forms of albinism (recessive).
•Some forms of haemophilia (recessive).
•Polydactyly - extra digits (dominant).
Genetic testing, counselling
•Genetic counselling can offer advice to people in families with known genetic
disorders.
•Carrier, fetal, newborn testing possible for some conditions.
•Key ethical issues remain surrounding use of technologies in this area.
P E D I G E E ANALYSIS
(for single locus traits)
1. AUTOSOMAL RECESSIVE (can hide)
a. two affected individuals have 10OX affected children
b. unaffected parents can have affected children
c. recessive alleles can hide from generation to generation d. both sexes
affected
2. AUTOSOMAL DOMINANT (can't hide)
a. trait typically appears in every generation
b. two affected individuals can have unaffected children c. both sexes affected
.. 3. X-LINKED DOMINANT (gene on X, expect more females)
a. unaffected parents cannot have affected children
b. affected father passes trait to all daughters but no sons
c. females affected more than males since two chances or better than one
.. 4. X-LINKED RECESSIVE (gene on X, more males)
a. affected mother always passes condition to sons, affected father never will
b. most coupon mode of transmission is from normal (carrier) female to son (50%
chance)
c. more males affected since males do not mask recessive X-linked alleles
5. Y-LINKED RECESSIVE (only males)
a. all sons of affected fathers will be affected b. females not affected and
cannot be carriers
6. SEX-LIMITED (primary or secondary sex trait)
a. only found in one sex, males have beards females have breasts
7. SEX-INFLUENCED, MALE DOMINANT (think baldness)
a. affected mother will have 100% affected sons
b. daughters must inherit a double dose to be affected (acts recessive) c.
affected father can transmit trait to sons
d. more males than females affected
8. SEX-INFLUENCED, FEMALE DOMINANT (rare)
a. affected fathers always have affected daughters b. two normal parents cannot
have an affected son c. more females than males
. Karyotyping
In 1961 an international meeting was held at the University of Colorado Medical
School in Denver, Colorado to standardize the format for a normal human
karyotype. The format that evolved is known as the "Denver System."
Each chromosome has its own individuality as shown by its size, shape, and
position of its kinetochore. Using the "Denver System," the chromosomes are put
into similar groups designated by letters. Then numbers are used to subdivide
the chromosomes within the groups designated by numbers based on the position of
the kinetochore and the length of the chromatids. The homologous chromosomes are
paired based on their banding.
. The student will obtain a normal male or female karyotype. Next, using
scissors, carefully cut out the individual chromosomes and arrange them on a
blank karyotype form with the kinetochore on the dotted line using the Denver
System Table and the sample karyotype as a guide. It is much easier if done in
the following order-group A, group B, group D, group F, group G, group E, and
group C last. Attach chromosomes to the karyotype form as directed.
After the normal karyotype is completed the student will be given an abnormal
karyotype. First, count the number of chromosomes on the sheet of paper. There
will be either 45, 46, or 47 chromosomes. Knowing the number of chromosomes will
be a big help in identifying the unknown karyotype.
.
Using scissors, cut out the chromosomes and arrange them on a blank karyotype
form with the kinetochore on the dotted line using the Denver System. It is much
easier if done in the following order-group A, group B, group D, group F, group
G, group E, and group C last. Attach chromosomes to the karyotype form as
directed
.