Science of
HEREDITY
Key Concepts*
studies how the
form
[morphology]
and appearance [phenotype] of an organism
are established by its
genes as influenced by the
environment.
essence of heredity...
from the millions of different species,
each reproduces itself, faithfully,
yielding progeny that belong to the
SAME species, i.e., the parent organism
hands
down information specifying, in exacting
detail, the characteristics of its offspring;
this phenomena of
Heredity is central to the
definition of Life...
ability of a cell to faithfully copy its DNA instructions into
identical progeny cells.
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a genetic pedigree |
Two aspects to heredity...
Mendelian Genetics -
Quantitative analysis of inheritance
of morphological characters in organisms....
experiments which established the basic principles &
laws
that
predict the pattern of inheritance from generation to generation
a genetic pedigree*
Molecular Genetics -
physical properties of molecules (DNA &
RNA)
as they effect patterns of inheritance
Central Dogma of Molecular Biology
DNA -->
transcription -->
RNA --
translation -->
Protein
MENDELIAN
GENETICS...
Mendel Museum
Gregor Mendel
was an Augustinian monk (later abbot) at the Abbey of St. Thomas
in Brno (today part of the Czech Republic)
bred
sweet pea
flowers* to produce progeny
via self
pollination*
&
cross
pollination*
Mendel made crosses between
true breeding parents
for a single genetic character (morphological
trait)
with 2 different
phenotypes (appearances)
Mendel's 7
true breeding traits in pea plant genetic crosses*
Concept Activity 14.2-
Gregor's Garden
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MENDELIAN EXPERIMENTAL MONOHYBRID CROSS... |
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generation
experimental genetic cross
Parental round seed x wrinkled seed
F1 round seed
[ x themselves]
F2
3
round* seed
to 1
wrinkled*
seed |
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Concept Activity - 14.1 - Mendel's Experiments :
Monohybrid Cross |
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another example using
flower color in peas* |
Particulate Inheritance
Physical inheritance is discernible as
"particles" or "factors",
which are
- discrete entities w own integrity (no blending of traits)
- trait is preserved through
inheritance
(over
generations)
- occur within the individual in
PAIRS (diploid)
- some particles
mask expression of others (round masks
wrinkled)
Law of Mendelian Segregation...
when gametes are formed
- 2 particles of
inheritance in an individual segregate from each other
- each gamete receives 1 particle from each parent
Modern Interpretation of Mendel's Hypothesis...
- particles are
GENES...
entities
definable in molecular terms
[DNA segment]
- referred to by alphabetic taxonomy =
A
& a, B
& b, C
& c, etc...
- trait may occur in different
morphological forms... called
ALLELES
allele - a gene which codes for different forms
(round, wrinkled,
square)
of a similar protein, that governs
that phenotype
alleles occur on chromosomes at
a specific GENE
LOCUS* -
- some traits mask expression of others -
dominant & recessive allele
traits
recessive - trait that
disappears in the F1 generation
dominant - trait that does not disappear in the F1
-
each individual possess 2 alleles for a specific trait,
thus
RR - homozygous dominant
Rr -
heterozygous
rr - homozygous recessive
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Mendelian
Monohybrid Genetic Cross |
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parental |
RR |
x |
rr |
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TRUE BREEDING |
round |
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wrinkled |
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gametes (4) |
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meiosis |
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haploid |
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F1* |
Rr |
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diploid |
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F2* |
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Punnett Square |
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flowers* |
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Results of Monohybrid Cross
PHENOTYPE (APPEARANCE)
3 round to 1 wrinkled
ratios*
GENOTYPE (ALLELE
MAKEUP) 1
(RR) to 2 (Rr) to 1 (rr) numbers*
Mendel's hypothesis
is scientifically testable
- his premise [a testable hypothesis]
predicts that F1 is a heterozygote [Aa]
- testable experiment - do a
Testcross/Backcross*
cross of
unknown genotype
to
homozygous recessive
| predict 1:1 ratio |
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r |
r |
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if
heterozygote |
R |
Rr |
Rr |
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r |
rr |
rr |
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| predict all the same |
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r |
r |
| if
homozygote |
R |
RR |
RR |
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R |
Rr |
Rr |
Link between GENOTYPE - PHENOTYPE
| genotype |
RR |
Rr |
rr |
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phenotype
seeds |
round |
round |
wrinkled |
| starch content |
high |
median |
low |
| starch grains |
numerous |
median |
few |
| reducing sugar |
low |
median |
high |
UDP-glucose
phosphorylase |
high |
median |
low |
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starch +
G1P
--> starch (n+1) |
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thus : dominant allele
R
of the seed shape gene codes for the enzyme
UDP-glucose (glycogen) phosphorylase
which makes starch,
which is hygroscopic and absorbs water,
 making the seed appear
round in the dry seed state.
Molecular Basis of
some of Mendel's
Traits...
in 1990 - the gene for wrinkled seed was
determined to be due to
the starch branching enzyme UDP-glucose (glycogen) phosphorylase
the
recessive was
caused by a
transposon-like insertion
[glossary]*
into the
starch branching enzyme's coding region
___________
in
1997 - in the pea plant (& in the plant
Arabidopsis)
gene called
Le
which controls stem length (mutants are shorter)
was identified
the gene codes for the enzyme: GA3b-hydroxylase,
which converts
two precursors of
Gibberellic Acid into active
GA3b,
GA3b is a plant hormone that promotes stem growth & fruit set.
Incomplete Dominance -
figure*
vs.
Blended
Inheritance
can it still be explained by Mendel's Law's?
-
yes. neither gene is dominant,
i.e., both contribute to expression of the trait
Mendel's
Law of Independent Assortment
a dihybrid cross
demonstrates Independent Assortment
dihybrid cross involves 2 characters or traits
-
new combinations of traits, not exhibited by either parent,
are seen
parentals - progeny look like parents
non-parentals
- progeny don't look like either parent
DOMINANT
RECESSIVE
flower color W = red
w =
white
seed color G = green
g = yellow
 P1
WWGG
x
wwgg
true breeding
F1
WwGg
(x WwGg
self cross)
what's the phenotype?
F2
phenotypes
flower color seed color
ratio
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parental |
red |
green |
9 of 16 |
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non-parental |
white |
green |
3 of 16
9:3:3:1 |
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non-parental |
red |
yellow |
3 of 16 |
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parental |
white |
yellow |
1 of 16 |
Each trait alone
red (3) = 12 of 16
white
(1) = 4 of 16
3:1
green (3) = 12 of 16 yellow (1) = 4 of 16
Chromosomal Theory of Inheritance*
Walter
Sutton
& Theodor
Boveri (1902-1903)
looked at
spematogenesis and oogenesis,
especially in grasshopper & sea urchins
described
chromosomes &
observed MEIOSIS & suggested...
- hereditary traits are carried in sperm & egg cells
- on
chromosomes
- chromosomes obey Mendel's laws
> chromosomes occur in pairs, as do "particles"
(homologs)
> chromosomes segregate at meiosis, as do "particles"
via Mendel's
Law of Segregation (homologs/chromatids
separate)
>
chromosomes sort
independently of each other
via Mendel's Law of Independent Assortment
-
fig 15.2 (laws)*
Golden Age of Genetics:
CHROMOSOMAL LINKAGE
Thomas Hunt Morgan ... Univ. of Columbia geneticist -
fruit fly*
[calvin
bridges]
sex
determination & genes & their traits are linked to specific
loci on chromosomes
2 types of
CHROMOSOMES -
1.
AUTOSOMES - the non-sex chromosomes
(everything else: 44 +
2)
KARYOTYPE* - photographic map of a species chromosomes
2.
SEX
chromosomes
(X and Y) - show a different
structural morphology
pic*
sex determination* -->
heterogametic sex (xy) &
homogametic sex (xx)
Y-chromosome
-
determines maleness &
holds Short Tandem Repeats
SEX LINKED Recessives* when
a
trait's gene is carried only on an X chromosome.
Xa
Xa vs. Xa Y
No Y trait thus... HEMIZYGOUS (males) figure*
ex:
red green
colorblindness (males = 8% and
females 1%)
others: hemophilia, albanism, myopia, Duchenes' M.D.
Sample Genetics Problems*
end material for
test #2
Autosomal Linkage...
(crossing
over
&
maps)
-
two
traits are carried on a single chromosome
___R__y__
-
do not sort independently
µ - crossing over will allow us to map position of genes
mapping - frequency of cross over exchange is
proportional
to relative distance between 2 genes.
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generation |
genotype |
phenotype |
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parental |
RRYY x rryy |
round/yellow wrinkled/green |
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F1 |
RYry |
round/yellow |
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Testcross |
RYry
x
ryry |
round/yellow wrinkled/green |
| ¥* |
if linked |
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if not linked |
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ry |
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ry |
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RY |
RYry |
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RY |
RYry (RrYy) |
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ry |
ryry |
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Ry |
Ryry (Rryy) |
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rY |
rYry (rrYy) |
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ry |
ryry (rryy) |
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1 : 1 |
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1 : 1 : 1 : 1 |
Mapping......
we do an actual F1 testcross of linked genes;
predicts 50:50
progeny.
BUT; get following
results... NOT
1 : 1 [RYry
&
ryry], but rather we get...
round & yellow
41.5% R_Y_ parental
phenotype
wrinkled & green 41.5% rryy
parental phenotype
round & green
8.5% R_yy non-parental
phenotype
wrinkled & yellow 8.5% rrY_ non-parental phenotype
(17% non parentals)
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HOW COME ??? because of
CROSSING OVER...
or homologous recombination... the process by which
two
non-sister chromatids, paired up during prophase 1 of
meiosis,
exchange equal distal portion of their chromosomal
DNA |
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A
B C |
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a
b
c |
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Frequency of crossover exchange...
exchange of chromatids
pieces of a homologous pair
during synapsis at a chiasma... |
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is GREATER the
FARTHER apart 2 genes are
is proportional to
relative distance
between 2 linked genes
Relative
distance is measured as...
1% crossover frequency =
1 map unit of map distance
above CO Freq = 8.5% + 8.5%
= 17%
1% CrossOver Freq
= 1 centiMorgan
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Let's determine
the map for the genes R [shape]
&
Y [color]
1.
Genes
R
&
Y
revealed 17% CO frequency of exchange (above)
thus genes
R and
Y are 17 map units (centiMorgans) apart
2.
now, genes R and X reveal
5% crossover frequency ???
3.
thus, genes
Y and X could reveal either
a 12% or 22% CO
frequency???
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X 5cm
. 5cm
X
RRXX x
rrxx --> RXrx
-> testcross |
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R
17cm Y
but 5% are R_xx &
rrX_ |
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R 5cm
X 12cm Y |
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X 5cm
R
17cm Y
YYXX
x yyxx -->
YXyx = % ? |
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µ
genes are
linear &
occur at specific loci
a mapping example* |
Gene Interactions...
and Mendelian
ratio
anomalies
Complementary Genes -
2 genes are
mutually dependent to show phenotype
Purple flower color requires
a color protein &
a protein complement
P
PPCC x ppcc
both required for phenotype
F1
PpCc
F2
9 P_C_ purple
3 ppC_
white
a
9
:
7 ratio
3 P_cc
white not 9:3:3:1
¥
1 ppcc
white
Epistasis* - works in similar fashion: often involves
B =
melanin gene;
where a gene at one locus
modifies the phenotype (C
= deposits pigment) of gene
at a second locus (Black or brown)
and results in an altered dihybrid ratio.
9 B_C_ 3
bbC_
3 B_cc 1 bbcc
9:3:7
black brown
white
Polygenic
[Quantitative Trait]
Inheritance
2 or more genes affect 1 phenotype
usually with quantitative characters,
with a continuous scale of measurement...
-
height, weight,
color* (and
a
polygenic*model), etc...
Pleiotropy
1 gene influences many
phenotypic traits...
- a mutant defect in collagen gene = multiple
morphological deformities...
as the main component of cartilage, ligaments,
tendons, bone and teeth.
-
sickle
cell gene results in many physiological disorders due to key
metabolic role that gene plays in physiology of blood
Classical Human Genetics
Some Examples of Human Genetic Traits...
-
Widow's peak* &
free ear lobes*, + finger hair
&
freckles,
-
Blood Groups*
- 4 phenotypes O, A, B, and AB
due to RBC surface carbohydrates
- Sex linkage - trait carried on X-chromosome
red-green colorblindness,
hemophilia* [
genealogy ]
-
Mistakes of Meiosis - abnormal chromosome structure
Downs Syndrome* -
Trisomy 21 - due to chromosome non-disjunction
& examples via non-disjunction in sex chromosomes
-
Inborn Errors of Metabolism -
defective enzymes due to recessive mutations
Inborn Errors of Metabolism -
non-functional
enzymes
[genes
& diseases]
PHENYLKETONURIA
- [PKU]
pp
1/10,000 births
disfunctional phenylalanine hydroxylase
on chromosome 12
PHE --x-->
tyrosine --> -->
degraded & excreted
accumulates - blood/brain barrier = mental retardation
ALKAPTONURIA
aa A. Garrod
in 1908 1/200,000
homogentisic acid oxidase --x-->
ALKAPTON*
[urine oxidizes black & ochronosis]
1st suggestion that effect of genes was to make proteins
and disease
is due to a defective enzyme/protein.
TAY SACHS
tt
1/300,000 births
defective (hexosaminidase-A) enzyme =
high ganglioside fats in nerves --> death
Ashkenazic Jewish
ancestry show 1/ 3,600
births & 1 / 30
is Tt
SICKLE CELL s ss 1/6,000 births
defective beta polypeptide of
Hb
improper folding of
Hb --> clogs capillaries
[umbilical cord blood stem cell transplant of
Keone
Penn
update]
How many recessive
alleles are there in a given population?
It is easy to
determine how many recessives there are in a
population -
Just
Count them, but...
[phenotype = aa &
shows strait]
but, How do we know
how many
Heterozygous Carriers there are in a population?
We can determine
the number of carriers for a recessive gene by
using...
Hardy-Weinberg
Equilibrium*
Chromosomal Abberations
- Mistakes of Meiosis
Aneuploidy -
Variation in chromosome #
monosomy - 1 less than normal
disomy - normal (diploid)
trisomy - 1 more than normal
via non-disjunction*
(trisomy 21
- Down Syndrome -
frequency vs. age*]
Aneuploidy of SEX chromosomes in the gametes:
(non-disjunction of XX)
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X X |
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0 |
+ |
XX |
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X0
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X
or Y |
Y0
XXX |
X or
Y |
XXY |
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Turner syndrome
1/5000 births
90% abort -
appears female
often sterile
TSS |
dies
triple X syndrome
1/1000 births
no visible symptoms
may be sterile
some developmental issues |
Kleinfelter
1/2000 births
appears male
sterile
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