Transcript inheritance and Mendelian genetics

inheritance and
Mendelian genetics
biology 1
• Mendel provided the experimental basis
for modern genetics
– Law of Segregation
– Law of independent assortment
• Use of probability in genetics
• Relationships between genotype and
phenotype
• Some human genetic disorders
Pre-mendelian beliefs
• Blending theory; traits blend like liquids,
heritable features become irreversibly
inseparable
– CON: individuals would eventually blend to a
uniform appearance between individuals
– CON: traits would not be able to re-appear once
blended
• Thus the blending theory was replaced by
the particulate theory of heredity in 1860s
Mendel
• Particulate theory of heredity:
– Parents transmit to their offspring discrete
inheritable factors (now called genes) that
remain as separate factors from one
generation to the next)
• Mendel demonstrated his theory by
breeding pea plants with specific
variants of trait contributing towards a
character
Definitions of Mendelian experimentation
• Parental (P) generation
• F1 generation - hybrid offspring of parental
generation
• F2 generation - offspring resulting from selfpollination of F1
• True breeding: always produces plants with
the same traits as parental generationr
• This experimentation resulted in Mendel
Laws - the law of segregation, and the law
of independent assortment
The Law of Segregation
• Each trait corresponds to an allele.
When breeding, each allele is packaged
into a gamete (ie., genes are not
blended)
– For example, true-breeding purple flower
crossed with true-breeding white flower
results in all-purple flower F1
– When F1 is self-pollinated, white flower
trait reappears in ratio of:
Purple:white = 3:1
• Mendel proposed that
– Alternative forms of genes are responsible for variation
in inherited characters (eg., for flower color gene, two
alleles - purple trait and white trait
– for each character, an organism inherits two alleles, one
from each parent (eg., homologous chromosones)
– If the two alleles differ, one is fully expressed (dominant
allele, denoted in upper case, eg., Purple = P), and one
is completely masked (recessive allele, denoted in lower
case, eg., white = p)
– The two alleles segregate during gamete production
(meiosis), thus gametes of true-breeders will carry the
same alleles to the offspring. BUT, if different alleles are
present in the parent, then there is a 50:50 chance of
which allele is passed on
• Thus Mendel’s Law of Segregation states
that allele pairs from homologous
chromosomes segregate during gamete
formation (meiosis), and the paired
condition is restored by the random fusion
of gametes at fertilization
– This law predicts a 3:1 ratio of phenotype in
the F2 of a monohybrid cross
– Simple mendelian problems such as this can
be calculated using Punnett squares
More vocabulary
• Homozygous - identical alleles in
homologous chromosomes (ie, PP, or pp) such organisms are true-breeding
• Heterozygous - different alleles in
homologous chromosomes (ie, Pp) - such
organisms are not true-breeding
• Phenotype - an organism’s expressed traits
• Genotype - an organism’s genetic makeup
The test-cross
• If some alleles are dominant over others,
there may be no way to determine genotype
from phenotype (e.g. PP vs Pp?)
• Use a test-cross to determine such questions
– Cross unknown with homozygous recessive
• If unknown is Homozygous dominant, then offspring
should all demonstrate dominant phenotype
• If unknown is heterozygous, the offspring should be
50:50 dominant trait to recessive trait
The Law of independent assortment
• Each pair of alleles segregates into gametes
independently
• To demonstrate this, consider the dihybrid cross
(this examines two characteristics simultaneously)
• Mendel bred true breeding plants with yellow round
seeds (YYRR, gamete = YR) against green
wrinkled seeds (yyrr, gamete = yr)
– Dihybrid F1 is heterozygous for both traits (YyRr)
– Under two models
• F2 progeny demonstrates non-independent assortment ratio of
3:1
• F2 progeny demonstrates independent assortment ratio of
9:3:3:1
Using probability in Mendelian genetics
• Segregation and random assortment are random
events, and can thus be characterized by
probability
• The two rules of probability state that:
• The probability of an outcome ranges from 0 to 1
• The probabilities of all possible outcomes for an
event sum to 1
• The outcome of a random event is unaffected by
the outcome of previous events
• If you cross Pp with itself, what is the probability of pp?
– For pp to occur, the two gametes that fuse must be p and p
– Probability of a Pp plant giving rise to a p gamete is 0.5
– Law of multiplication states that
p(pp) = p(p) x p(p) = 0.5 x 0.5 = 0.25
• In a dihybrid cross (YyRr x YyRr), what is the probability of
YYRR?
– For YYRR to occur, the two gametes that fuse must be YR
and YR
– Probability of a YyRr plant giving rise to a YR gamete is 0.25
– Law of multiplication states that
p(YYRR) = p(YR) x p(YR) = 0.25 x 0.25 = 0.0625
• Probability’s Law of addition can also be
used:
• In a monohybrid cross of heterozygotes,
what is the probability of a heterozygote
offspring?
• Dominant sperm fuses with recessive egg:
p(P) x p(p) = 0.5 x 0.5 = 0.25
• Recessive sperm fuses with dominant egg
p(p) x p(P) = 0.5 x 0.5 = 0.25
• p(Pp) = p(Pp) + p(pP) = 0.25 + 0.25 = 0.5
The relationship between
genotype and phenotype
• Mendel was fortunate to select for his subject
material a simple system
• Dominance does not imply abundance
• Dominance relationships vary on a continuum
from
– Complete dominance (AA and Aa have the same
phenotype)
– Incomplete dominance (Aa is an intermediate
phenotype)
– Codominance (Aa = both alleles expressed
simultaneously)
Multiple Alleles
• More than two alleles possible for a
gene - for example, blood; IA, IB, i
Blood type
Possible
genotypes
Antigens on
red blood cell
Antibodies in
the serum
A
IAIA
IAi
A
Anti-B
B
IBIB
IBi
B
Anti-A
AB
IAIB
A, B
-
O
ii
-
Anti-A
Anti-B
Pleiotropy
• The ability of a single gene to have
multiple phenotypic effects
• e.g., sickle cell anemia causes multiple
symptoms, only one of which is the
actual sickle celled condition
Epistasis
• A condition in which a gene at one locus
can effect the phenotypic expression of
a second gene
• Epistasis between two nonallelic genes
causes deviation from the predicted
9:3:3:1 Mendelian ratio
• For example, in mice, fur color
controlled by two genes - C (melanin
deposition, and B (Black versus brown)
Polygenic inheritance
• A mode of inheritance in which the additive
effect of two or more genes determines a
single phenotypic character
• For example, skin pigmentation is controlled
by at least 3 genes, A B and C
– AABBCC results in darkest shade
– aabbcc results in lightest shade
• Each gene contributes equally
AaBbCc = AABbcc
• Environmental factors may also effect shade
Human Genetic Disorders
• Recessive alleles that cause human
disorders are usually defective versions of
normal alleles
– Defective alleles usually code for a
malfunctioning or no protein at all (some
heterozygote protection)
• Recessive inherited traits range from nonlethal
(albinism) to lethal (cystic fibrosis)
• These traits are only active in the case of
homozygous recessive
• Heterozygotes are carriers
• Cystic fibrosis occurs 1/2500 in caucasian populations. 4%
of caucasians are carriers. Dominant allele codes for
production of membrane protein that controls intake/outake
of chloride. Homozygous recessive individuals unable to
control chloride passage. Disease symptoms result form
build up of fluid in lungs and pancreas
• Tay Sachs disease occurs 1/3600 (incidence is higher in a
particular group of jewish people). Brain cells are unable to
breakdown a vital lipid that interferes in the CNS.
Accumulation of lipid causes seizures, blindness and
deterioration of motor performance
• Sickle cell anemia effects 1/400 african-americans.
Caused by a single amino acid substitution in hemoglobin.
Sickle cells clog arteries. Approx. 1/10 african-americans
are heterozygous carriers. Codominance of allele means
heterozygotes can survive effects of disease (also helps
battle malaria)
• Dominantly inherited disorders are rarer,
since their presence cannot be hidden
in a heterozygote
– include Huntingdon’s disease, a
deterioration of the nervous system
• Multifactorial disorders are diseases
that have both an environmental and
genetic basis, including
– Heart disease, diabetes, cancer,
alcoholism, and some forms of mental
illness