SAN DIEGO MESA COLLEGE
General Biology (BIO107)
LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
Chapter 9: Genetics & Mendel’s principles
G
Geenneettiiccss

Genetics is a relatively young and very dynamic sub-discipline of Biology

Genetics is the scientific study of heredity of living organisms; i.e. the passing on
of characteristics from parents to their offspring
 geneticists study how the smallest units of heredity – the genes –
are passed on from one generation to the other

The science of genetics came a long way in human history
H
Hiissttoorryy ooff ggeenneettiiccss
A
Anncciieenntt G
Grreeeeccee: H
Hiippppooccrraatteess suggested the idea of Pangenesis to explain heredity
 according to this hypothesis, genes travel from one body to the
sperms and eggs of another body
E
Eaarrllyy 1199ttthhh cceennttuurryy: JJeeaann--B
Baappttiissttee P
P.. A
A.. ddee LLaam
maarrcckk (1744-1829) states the so-called
blending hypothesis which dominated the scientific thoughts about heredity
 according to his hypothesis, hereditary traits of each
parent are mixed (= blended) to form a novel trait in the
offspring
 he also stated that acquired characteristics are inherited
E
Eaarrllyy 11886600ss: the Austrian monk G
Grreeggoorr M
Meennddeell observes that certain traits of the
garden pea are inherited by (as he called it by that time) heritable factors in a
predictable way  he writes his famous “Principles of genetics” (1865)
11887766:: H
Hoorrnneerr, a British physician recognizes for the first time red-green color
blindness as a "sex-linked" inherited disease
 he observed in that color blindness is inherited in boys from
mothers whose brothers had the problem
11889922:: A
A.. W
Weeiissm
maannnn proposes that chromosomes play a central role in heredity
A
Abboouutt 11991100:: the American biologist TT.. H
H.. M
Moorrggaann discovers that the genes
responsible for heredity are located on cell structures called chromosomes
 he concluded from crossing experiments with the fruit-fly Drosophila that
genes occasionally cross-over from one chromosome to another
eeaarrllyy 11990000ss: the Dutch botanist H
H.. ddee V
Vrriieess observed and described unexpected
differences in characteristics of offspring which were caused by changes in the genes
 he called these gene changes mutations
1
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General Biology (BIO107)
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Instructor: Elmar Schmid, Ph.D.
eeaarrllyy 11994400ss: the American geneticists G
G.. W
W.. B
Beeaaddllee &
&E
E.. LL.. TTaattuum
m discover that some
genes control the production of enzymes  genetic control of protein expression!
11994400ss: scientists discover that genes are segments of DNA; DNA is recognized as the
blue-print molecule of heredity
11995533:: FF.. C
Crriicckk &
& JJ.. W
Waattssoonn describe the molecular structure of the genetic material;
they state that the hereditary molecule DNA forms double helix, in which the bases are
base-paired
LLaattee 11996600ss:: the scientists S
Stteew
waarrtt LLiinnnn and W
Weerrnneerr A
Arrbbeerr isolate for the first time a
restriction endonuclease, an enzyme responsible for phage growth restriction in
Escherichia coli and which cleaves DNA at a wide variety of locations along the length
of the molecule
11996600ss aanndd 7700ss: scientists discover more enzymes which are able to cut DNA or glue
DNA strands together; they also discover extra-chromosomal DNA, called plasmids, in
bacteria, which soon become successfully exploited as important ‘tools’ in a new
discipline called genetic engineering
 genetic engineering becomes one of the most valuable and exciting
tool in genetic research and ‘biotechnology’
11997700ss:: P
P.. D
Duueessbbeerrgg &
&P
P.. V
Vooggtt discover the first oncogene, a gene which is implicated
in many human cancers.
A
A.. LLeevviinnee,, LL.. C
Crraaw
wffoorrdd &
&D
D.. LLaannee discover p53, the gene most commonly mutated in
human cancers
TTooddaayy:: American and European research teams read the complete sequence of the
human genome (all 3,000,000,000 DNA base pairs in our cell nucleus !!); this
information opens the door to a better understanding and diagnostics of human genetic
disease
 to the scientists surprise, the human genome contains less genes than
expected; only about 40,000 genes
2
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General Biology (BIO107)
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Instructor: Elmar Schmid, Ph.D.
G
Geenneettiicc TTeerrm
miinnoollooggyy

Before going into more details and try to understand the principles and intricate
mechanics of inheritance, we first must make ourselves familiar with the terminology
as it relates to genetics and heredity.

Inheritance, i.e. the passing on of heritable traits in biological organisms, has a lot to
do with genes, alleles, chromosomes, meiosis, breeding, genotype and phenotype
1. Gene:
 an approx. 500 – 1000 base-pair long segment of the DNA molecule that is
responsible for the manufacturing (= synthesis) of a protein ( s. protein
translation)
 the protein may be either become a part of the organisms structure or
become an enzyme responsible for the control of biochemical events in the
cell
 every gene has a unique location (= locus) on a distinct chromosome, which
can be unraveled by a scientist using a process called genetic mapping
 today, the location of many genes on the 46 human chromosomes has been
pin-pointed by geneticists, but gene mapping is an ongoing task in modern
molecular genetics
2. Chromosome
 long DNA fragment as part of the total cellular DNA (=genome) that heavily
folds and coils up into the typical X-shaped and visible chromosome form
during cell division and meiosis
 every biological organisms has its genomic DNA fragmented into a definite
number of chromosomes
 the otherwise non-visible chromosomes are called chromatin (= DNA plus
proteins)
3. Homologous chromosomes
 are the pairs of identical shaped and sized chromosomes in the cells of
more complex, diploid organisms
 they are the result of sexual reproduction after fusion of male and female
haploid gametes, each having only one set of chromosomes, to form a new,
diploid organism
 diploid organisms have two of each kind of chromosomes; they have two
complete sets of homologous chromosomes
 since genes are located on chromosomes, diploid organisms have two of
each kind of genes located on the same loci on the homologous
chromosomes
4. Alleles
 are alternate forms of a particular gene located on the identical locus on
either homologous chromosome in the cells of diploid organisms
 each allele is contributed from a different (maternal or paternal) individual
3
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

LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
allele pairs have the genetic information for the same trait and are located at
the exact same spot on homologous chromosomes
but since each allele originated in a different individual it does not have the
exactly identical gene (sequence); it has slight DNA variations due to
mutation events
5. Genotype
 is the description of the alleles an individual possesses for a particular trait
 usually written as a one-letter code, e.g. YY or AB
 if an organisms has two identical alleles located on its homologous
chromosomes, we call this organisms homozygous for that specific trait, e.g.
AA
 if an organism has two different alleles located on its homologous
chromosomes, we say that it is heterozygous for that trait
6. Phenotype
 the physical (= body/tissue/cell) expression of the genetic information of
the alleles of a biological organism
 since there are different possible combinations of alleles (2 sets in a diploid
organism!), there are alternative possible phenotypes for a particular trait
TThhee rruulleess ooff ggeenneettiiccss ((oorr M
ME
EN
ND
DE
ELL’’S
SP
PR
RIIN
NC
CIIP
PLLE
ES
S))

The beginning of our modern understanding of heredity and inheritance patterns we
owe the tedious and ingenious breeding experiments of Gregor Mendel which he
performed in the 1850s in Brna (located in Czechoslovakia). Around 1857, Mendel
began breeding garden peas to study inheritance.

Mendel chose the common garden pea to conduct his famous breeding experiments
 his experiments led to the discovery of the fundamental principles of genetics
and marked the beginning of the era of modern genetics

The garden pea had a series of favorable features which were largely responsible
for Mendel’s experimental success
1. it is easy to grow and is available in many readily distinguishable varieties
 e.g. blossom color, seed shape, pod color, etc.
2. he could exercise strict control over plant matings by switching between the
natural process of self-fertilization and the experimental procedure of cross
fertilization
 he was able to control the parentage of the new plants
3. he could select from a series of easy-to-follow, heritable plant characteristics
(see graphic)
 Mendel chose seven of these characteristics, i.e. flower color,
4
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flower position, seed color, seed shape, pod shape, pod color
and stem length for his breeding studies
4. he worked with his plants and plant characteristics, until he could be sure to have
so-called true-breeding varieties. A true-breeding variety is a variety for which
self-fertilization produced offspring all identical to the parent
 with his true-breeding varieties he performed his famous
breeding experiments to generate hybrids
 hybrids are the offspring of two different, true-inbreed varieties

The cross fertilization of two true-inbred parental plants (= P generation) to
generate hybrid offspring (= F1 generation) is also called hybridization or a cross

Mendel created first an F1 generation of hybrid offspring after crossing two trueinbreed parental plants which differed in only one variety e.g. flower color or seed
color
E
Eaassyy ddiissttiinngguuiisshhaabbllee hheerriittaabbllee ttrraaiittss iinn tthhee ggaarrddeenn ppeeaa
•
Each pea plant has male, pollen-producing stamens and female, egg-producing
ovaries (located in the carpal) as sexual organs. In nature, many plants have the
capacity to self-fertilize, fertilizing ova with their own sperm, despite the common
observation that most plants are fertilized in nature with pollen grains derived from
another plant of the same species via cross fertilization with the help of a pollinating
animal, such as a honey bee or a cricket.
•
In his famous “mono-hybrid cross” experiments, Mendel transferred pollen from one
pea plant to another pea plant to cross-pollinate in a highly controlled manner.
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Mendel’s cross pollination of true bred garden pea varieties
M
Meennddeell’’ss ccrroossss bbeettw
weeeenn 22 ttrruuee--iinnbbrreedd ppaarreennttaall ppeeaa ppllaannttss
Phenotype
P
P--ggeenneerraattiioonn
Genotype
FF11--ggeenneerraattiioonn
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
Mendel observed that all hybrids in F1 generation had only yellow, round seeds
or purple flowers and no mixed colors or shapes
 this observation strongly spoke against the blending hypothesis which has
been stated earlier by J.B. Lamarck

In the second step he self-fertilized or cross-fertilized this F1 generation and
studied the distribution of his characteristics, e.g. flower color or seed color, in
the next, so-called
F2 generation

By mating the F1 plants Mendel discovered the re-appearance of the green
seed color in ¼ of all F2 plants, while the rest ¾ had yellow seed color again
M
Moonnoohhyybbrriidd ccrroossss eexxppeerriim
meenntt
7
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Heritable trait  Seed color
Cross
Outcome
Plant1
Plant2
(Offspring)

PunnettSquare
Heritable trait  Petal color
Mendel’s Interpretation: Genes or alleles responsible for heritable traits segregate
during gamete formation
 Mendel’s Law of Segregation
8
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
Mendel concluded from this monohybrid crossing experiments, that his pea plants
carried two hereditary factors for the plant characteristic “seed color”; and that the
seed color yellow dominated the expression of the green seed color in the F1
generation

He performed several of these classical so-called monohybrid crosses. In all these
experiments he tracked the inheritance of one single characteristic of two trueinbred parent plants. For example, parent plants with either white or purple flower
color or parent plants with yellow or green seeds

From identical results from other monohybrid cross experiments with different
characteristics, e.g. blossom color or pod shape, Mendel formed 4 hypotheses (=
Mendel’s Principles)
 each of the seven characteristics he studied showed the same
inheritance pattern
9
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General Biology (BIO107)
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M
Meennddeell’’ss pprriinncciipplleess
1. There are alternative forms of genes that determine heritable traits. Alternative
version of genes (different alleles) account for variations in inherited characters.
- Different alleles vary somewhat in the sequence of nucleotides at the
specific locus of a gene.
- The purple-flower allele and white-flower allele are two DNA variations at the
flower-color locus.
2. For each inherited character or trait an organism has two alleles/ genes
 one from each biological parent
 they may be the same allele or may be different
3. Male sperm/pollen or female oocytes (eggs) carry only one allele for each
inherited trait
 Allele pairs segregate from each other during the production of
gametes in meiosis
 after fertilization of egg and sperm each allele contributes to the paired condition
in the offspring
4. When two genes of a pair are different alleles and one is fully expressed while the
other one has no noticeable effect on the organisms appearance, the alleles are
called dominant and recessive alleles, respectively
M
Meennddeell’’ss pprriinncciippllee ((oorr llaaw
w)) ooff sseeggrreeggaattiioonn

In sexually reproducing biological organisms, only the trait information on one gene
(= of one the two alleles) is put into each gamete formed during meiosis. It states
that genes or alleles segregate during gamete formation. Fusion of gametes
during fertilization pairs the genes again.
10
SAN DIEGO MESA COLLEGE
General Biology (BIO107)
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S
Seeggrreeggaattiioonn ooff aalllleellee ppaaiirrss dduurriinngg m
meeiioossiiss iinn tthhee ggoonnaaddss
((ddiippllooiidd))
pre-germ cell

((hhaappllooiidd))
sperm or egg cell

S
Seeggrreeggaattiioonn ooff aalllleellee ppaaiirrss dduurriinngg m
meeiioossiiss
S
S = dominant allele
ss = recessive allele
11
SAN DIEGO MESA COLLEGE
General Biology (BIO107)
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
Mendel’s law of segregation accounts for the 3:1 ratio that he observed in the F2
generation. The F1 hybrids will produce two classes of gametes, half with the purpleflower allele and half with the white-flower allele. During self-pollination and
fertilization, the gametes of these two classes unite randomly. This can produce four
equally likely combinations of sperm and ovum.

If after fertilization, an organism has the genotype, e.g. S
Sss, we call this organism
heterozygous regarding the Allele ‘S’. If after fertilization an organism has the
genotype S
SS
S or ssss, we call this organism dominant or recessive homozygous
regarding the Allele ‘S’ or ‘s’

Homozygous organism
 is a true-breeding organism with a pair of identical alleles for a certain
characteristic or trait
 e.g. Y
YY
Y or yyyy for the seed color of the garden pea

Heterozygous organism
 an organism with two different alleles for a heritable characteristic
 e.g. the F1 hybrids in Mendel’s experiment were all Y
Yyy, with the dominant
allele Y which carries the gene for the yellow seed color
12
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•
LIFE SCIENCES DEPARTMENT
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A Punnett square predicts the outcomes/results of a genetic cross between
individuals of known genotype. A Punnett square analysis of the flower-color
example demonstrates Mendel’s model. One in four F2 offspring will inherit two
white-flower alleles and produce white flowers. Half of the F2 offspring will inherit
one white-flower allele and one purple-flower allele and produce purple flowers. One
in four F2 offspring will inherit two purple-flower alleles and produce purple flowers
too. Mendel’s model accounts for the 3:1 ratio in the F2 generation.
Punnett Square
13
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TTeesstt C
Crroossss
H
Hoow
w ccoouulldd M
Meennddeell bbee ssuurree ttoo hhaavvee ttrruuee--iinnbbrreedd ppeeaa ppllaannttss hhoom
moozzyyggoouuss ffoorr aann
aalllleellee??

It is not possible to predict the genotype of an organism with a dominant phenotype.
The organism must have one dominant allele, but it could be homozygous dominant
or heterozygous.

A solution to this dilemma is a test cross. A test cross is a breeding experiment,
where a (known) homozygous recessive genotype is crossed with a dominant
phenotype with an unknown genotype. A test cross is a helpful tool to determine the
identity of an unknown genotype of a certain species.

Mendel performed many test crosses with his plants to determine the plant's
genotype and to assure himself that he worked with defined genotypes during this
performed breeding experiments.

Generally, in a test cross, an individual with an unknown genotype (e.g. Y
YY
Y or Y
Yyy ) is
crossed with an individual with a known homozygous, recessive genotype. In the
example case above, it would be a true-breeding pea plant with green seeds and
the yyyy genotype.

Suppose you were given a pea plant with the “yellow seed” phenotype. It’s genotype
could be either one of two possibilities: either Y
YY
Y or Y
Yyy

The outcome of a test cross, means the distribution of the phenotype, will tell about
the hidden, second allele of the heterozygous individual. Today, geneticist use the
test cross to determine unknown genotypes in agricultural plants or domestic
animals, such as dogs.
14
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TTeesstt ccrroossss
C
Caassee 11::
U
Unnkknnoow
wnn genotype:
Y
YY
Y

Y
Y
Y
Y
sperm
or
egg cells
Y
Yyy
Y
Yyy
yy
Y
Yyy
Y
Yyy
yy
yy yy
known genotype:
If the genotype of the unknown pea plant was homozygous, dominant (=
YY) regarding the trait seed color, then all of the resulting offspring (=
100%) will have yyeelllloow
w seed color
C
Caassee 22::
U
Unnkknnoow
wnn genotype:
Y
Yyy
Y
Y
yy
sperm
or
egg cells
Y
Yyy
yyyy
yy
yy yy
Y
Yyy
yyyy
known genotype:
yy

If the genotype of the unknown plant was heterozygous (= Yy) regarding
the trait seed color, then the outcome of the cross will be :  50% of all
offspring have yyeelllloow
w seed color; 50% have ggrreeeenn seed color

A so-called Punnett square helps to illustrate the possible combinations of
alleles of F1 gametes in the F2 generation after crossing
 it helps to visualize the genotypic distribution of alleles of one trait
15
SAN DIEGO MESA COLLEGE
LIFE SCIENCES DEPARTMENT
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
Because an organisms appearance does not always reveal its genetic
composition , geneticist distinguish between an organisms phenotype (= its
outer appearance), e.g. yellow or green seed color; blue or brown eyes, and the
genotype (= its collection of genes and alleles), e.g. Y
YY
Y or Y
Yyy or yyyy
TThhee cchhrroom
moossoom
mee tthheeoorryy ooff iinnhheerriittaannccee

Mendel’s principles were not understood until cell biologists discovered and
described the process of mitosis and meiosis in more detail
 especially the observed parallels of the behavior of the
chromosomes in both processes with the behavior of
Mendel’s heritable factors lead to the conclusion, that:
1. The behavior of chromosomes during mitosis and meiosis accounts for the
inheritance pattern of Mendel’s factors
2. Genes are located on chromosomes
 Mendel’s principle of iinnddeeppeennddeenntt aassssoorrttm
meenntt corresponds to Metaphase I of
meiosis, while Mendel’s principle of sseeggrreeggaattiioonn corresponds to M
Meettaapphhaassee IIII of
meiosis
 Alleles (= alternative forms) of a gene reside at the same locus on homologous
chromosomes
 the typical labeled bands on the chromosomes one observes in a Karyogram
represent a few gene loci
 the matching colors on both homologous chromosomes (band pattern)
highlight the fact that homologous chromosomes have genes for the same
characteristics located at the same positions
 but one band is not identical with one allele but rather shows about 10-100
gene
Mendel extended his studies with the garden pea from monohybrid cross experiments
and started to conduct so-called dihybrid cross experiments. In these he crossed
true-bred parental pea varieties which differed in not only one but TWO heritable
characteristics.
16
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D
Diihhyybbrriidd ccrroossss

In his initial breeding experiment, where Mendel followed the inheritance of flower
color or other characters, e.g. seed color, he focused on only a single character via
monohybrid crosses.

But he did not stop there. He also conducted experiments in which he followed the
inheritance of TWO different characters, by performing dihybrid cross experiments.

In one set of these ground breaking experiments, Mendel crossed homozygous
plants with dominant yellow, dominant round seeds (= genotype: Y
YY
YS
SS
S) with
homozygous plants with recessive green, recessive wrinkled seeds (= genotype:
yyyyssss)

His experiments resulted in F1 plants which all (100%) had the round and yellow
phenotype; they therefore had the genotype Y
YyyS
Sss

When he studied the phenotype of the F2 generation his results supported the
hypothesis that the genetic information was not inherited as a “linked package”, but
that each allele for each trait segregates independently during gamete
formation. By performing these experiments he discovered the famous “Principle of
independent assortment”.
M
Meennddeell’’ss pprriinncciippllee ooff iinnddeeppeennddeenntt aassssoorrttm
meenntt
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D
Diihhyybbrriidd ccrroossss w
wiitthh FF11 ppllaannttss

When sperm with four classes of “non-linked” alleles and ova with four classes of
“non-linked” alleles are combined, there would be 16 equally probable ways in which
the alleles can combine in the F2 generation.

These combinations produce four distinct phenotypes in a 9:3:3:1 ratio. This
hypothesis is consistent with Mendel’s results. This finding is also called Mendel’s
principle of independent assortment.

The principle of independent assortment applies also to the inheritance patterns
observed in many other sexually reproducing life forms, such as the inheritance of
feather colors in budgies. In these birds, two genes are involved, each with two
alleles (B and b, C and c). Birds with a B allele have yellow pigment in their feathers,
while birds with a C allele have dark melanin pigment which makes their feathers
18
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blue or darkish colored. Birds with the recessive b or c allele produce no pigment
and are therefore white-feathered.
TThhee rruulleess ooff pprroobbaabbiilliittyy aappppllyy ttoo M
Meennddeell’’ss pprriinncciippllee ooff iinnhheerriittaannccee

Mendel knew, due to his strong background in mathematics and statistics, that he
had to count many offspring from his crosses in order to reliably interpret inheritance
patterns.

Mendel’s laws of segregation and independent assortment reflect the same
(mathematical) laws of probability that apply to tossing coins or rolling dice. The
probability scale ranged from zero (an event with no chance of occurring) to one (an
event that is certain to occur).

To understand the laws of probability, tossing a coin or rolling a dice are good
examples. For example, the probability of tossing heads with a normal coin is ½,
while the probability of rolling a 3 with a six-sided die is 1/6, and the probability of
rolling any other number is 1 - 1/6 = 5/6.

The probability scale ranges from 0 to 1
 an event that certainly occurs has the probability “p” of 1
 an event that is not expected to happen has a probability “p” of 0
 e.g. for coins each toss has a p of ½ for head or tail
 each toss is a so-called independent event, which means
that the outcome of any particular toss is unaffected by the previous one
 p is always ½ for each toss
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 p for two heads after tossing two coins is calculated by applying the rule of
multiplication;
p = ½ x ½ = ¼ for two heads on the table after one toss

The rules of stochastics applied to genetics means, that the probability for any
genotype can be predicted if the genotype of the parents is known. For example,
the probability that 2 alleles come together at fertilization is ½ x ½ = ¼.

The probability of a certain genotype to occur in the F2 generation, which is
heterozygous for a specific allele (Aa), can be calculated by applying the so-called
rule of addition to that statistical problem
 this rule states, that the probability is the sum of the separate probabilities
 the probability for a heterozygous F2 genotype to occur is therefore:
¼ (A) + ¼ (a) = ½ (Aa)

By applying the rules of probability to chromosomal segregation and independent
assortment even complex genetic problems can be solved without the use of an
often arduous to perform Punnett square.

For example, the outcome of a tri-hybrid cross of two F1 individuals with three
different characteristics (= genotype: AaBbCc) can be predicted
 since each allele pair assorts independently this tri-hybrid cross
can be treated as 3 separate monohybrid crosses
 to calculate the probability of the appearance of the recessive homozygote
aabbcc, the so-called rule of multiplication is applied to solve the problem
Aa x Aa 
Bb x Bb 
Cc x Cc 
p of aa
p of bb
p of cc
= ¼
= ¼
= ¼
P (aabbcc) = ¼ aa x ¼ bb x ¼ cc = 1/64
 the same result (with a little more effort!) could be retrieved by
construction of a 64-section Punnett square

Generally, one can combine the rules of multiplication and addition to solve complex
problems in Mendelian genetics. For example, to determine the probability that an
offspring (F1) that is born to parent with the genotype aaBbCc and the genotype
AaBbCc and which has the F1 genotype AaBBcc can be calculated in following
way.

The individual allele probabilities for the F1 genotypes is as following:
p (Aa) = ½; p (BB) = ¼ and p (cc) = ¼
20
SAN DIEGO MESA COLLEGE
General Biology (BIO107)

LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
The probability for an offspring being born with the genotype AaBBcc is then
calculated using the product rule as following:
p (AaBBcc) = ½ x ¼ x ¼ = 1/32

Most of the genetic traits and characteristics of an individual are encoded and
located on autosomes. They are inherited in the typical Mendelian, means,
dominant-recessive pattern.

But many traits in biological organisms, including humans are encoded and laid
down on sex or gender chromosomes. Consequently, they are inherited in a
gender or sex-linked manner (see  X-linked inheritance).
Dominant-Recessive inherited traits in humans (Human Genetics)
Mendel’s principles apply also to the inheritance of many genetic traits in humans

Human cells like the cells of the garden pea have their genetic information encoded
on genes which are packed into chromosomes

Human cells also produce haploid germ cells (= sperm and oocytes) by meiosis and
reproduce by fertilization

Therefore, even though human cells contain many more genes ( around 100,000 !!)
than the garden pea, many heritable traits in humans follows the same Mendelian
principles of inheritance

Many human traits are known, which are determined by simple dominant-recessive
inheritance at one gene locus
R
Reecceessssiivvee oorr ddoom
miinnaanntt ttrraaiittss iinn hhuum
maannss
Trait
eye color
earlobe
freckles
PTC paper
finger number
hairline
Allele
ddoom
miinnaanntt
brown
free lobes
yes
able to taste
six
Widow’s peak
rreecceessssiivvee
blue
attached
no freckles
not able to taste
five
straight line
21
SAN DIEGO MESA COLLEGE
General Biology (BIO107)
LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.

Recessive phenotypes ‘no freckles’, straight hairline, not able to taste the bittertasting chemical PTC, and attached earlobes, require a homozygous, recessive
genotype aa to become visible in an individual.

Human traits of inheritance are much more difficult to analyze because one can only
study the result of matings (‘crosses’) that have already occurred. In this regard it is
important to collect information about the family history of that specific trait (=
genealogy) and to put this information in a so-called family-tree – the family
pedigree.

Many inherited disorders in humans are controlled by a single gene. More than 1000
dominant or recessive traits are known. These traits show therefore simple
inheritance patterns, which can be described and predicted by Mendel’s principles.

With the knowledge of Mendel’s principles and with the help of the laws of
probability, the fraction of offspring affected by a certain trait can be predicted

2 forms of heritable disorders are known in humans
II..
R
Reecceessssiivvee ddiissoorrddeerrss

Recessive disorders are disorders which only appear in individuals who are
homozygous regarding the recessive allele (e.g. people with an aa - genotype)

But many otherwise healthy individuals are so-called carriers of a recessive allele
which is responsible for a certain disease (they have an Aa – genotype). Examples
of recessive human disorders are:
11.. H
Heerreeddiittaarryy ddeeaaffnneessss
22.. C
Cyyssttiicc ffiibbrroossiiss ((C
CFF))
It is the most common lethal genetic disease in the US. The normal allele codes for a
membrane protein that transports Cl- between cells and the environment.
22
SAN DIEGO MESA COLLEGE
General Biology (BIO107)
LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
If these channels are defective or absent, there are abnormally high extracellular levels
of chloride that causes the mucus coats of certain cells to become thicker and stickier
than normal.
This mucus build-up in the pancreas, lungs, digestive tract, and elsewhere favors
bacterial infections.
Without treatment, affected children die before five, but with treatment can live past their
late 20’s.
The responsible allele is differently distributed amongst different ethnic groups. One in
25 whites is a carrier of CF.
Probability p
1/1800
1/17000
1/90000
Caucasian Americans births
African American births
Asian American births
A homozygous individual (= with 2 copies of the defect CF allele) develops the disease.
Some genetic tests can be detected at birth by simple tests, e.g.
combined amniocentesis/karyotyping or FISH, that are now routinely
performed in hospitals.
33.. P
Phheennyyllkkeettoonnuurriiaa ((P
PK
KU
U))
This recessively inherited human disorder, phenyketonuria (PKU) occurs in one in
10,000 to 15,000 births.
Individuals with this disorder have a lack or a dysfunctional enzyme due to a mutation in
the gene coding for this enzyme. As a consequence the amino acid phenylalanine and
its derivative phenypyruvate accumulate in the blood to toxic levels. This leads to
serious mental retardation of the affected new born.
If the disorder is detected, a special diet low in phenyalalanine usually promotes normal
development.
Amniocentesis & Karyotyping
23
SAN DIEGO MESA COLLEGE
General Biology (BIO107)
LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
44.. S
Siicckkllee cceellll aanneem
miiaa
Homozygous persons have sickled red blood cells, which cause serious damage to
many tissues in the body. This disorder affects one out of 500 births of AfricanAmericans; and 1 out of 10 African Americans is a heterozygote carrier of the sickle cell
allele. It is a very rare disease amongst other ethnic groups.
Heterozygous carriers of the sickle cell anemia allele are naturally more resistant
against Plasmodium falciparum infection and do not show the severe symptoms of
Malaria caused by this serious human pathogen.
24
SAN DIEGO MESA COLLEGE
LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
General Biology (BIO107)
44.. A
Allbbiinniissm
m
People or mammals affected by this rare autosomal recessive disorder lack the UV
light absorbing and DNA protecting pigment melanin in their skin, hairs and eyes. Their
skin or fur therefore appears white and the iris of their eyes appears red colored.
Affected persons or mammals (= albinos) are very easily sunburned and have a high
risk of developing forms of skin cancer.
Hypothetical family pedigree showing inheritance of the albino trait
female
male
female
male
I.
Genotype:
1
2
3
4
Aa
Aa
AA
aa
II.
Genotype:
1
AA
2
AA or Aa
3
aa
4
Aa
5
Aa
2
AA or Aa
3
aa
6
Aa
7
Aa
8
AA
III.
1
Genotype AA or Aa
:
Graphic©E.Schmid/2004
4
AA or
Aa
5
AA or Aa
Red = family members with albinism
25
SAN DIEGO MESA COLLEGE
General Biology (BIO107)
LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
M
Maannyy rreeaassoonnss aaccccoouunntt ffoorr tthhee m
maanniiffeessttaattiioonn ooff aa rreecceessssiivvee ggeenneettiicc ddiissoorrddeerr
w
i
t
h
i
n
a
h
u
m
a
n
p
o
p
u
l
a
t
i
o
n
within a human population
1. Prolonged geographic isolation and inbreeding

There is an increased probability that a recessive allele breaks through, i.e. it
becomes dominant in an homozygous individual if close relatives marry and have
children.

The manifestation of recessive disorders can frequently be observed in small
societies which were geographically isolated for extended periods of times (e.g. on
an island, in a hard-to-reach valley, etc.). Hereditary deafness is common amongst
certain families living on Martha’s Vineyard in Massachusetts.
2. Co-evolutionary aspects & Adaptive reasons

The allele for sickle cell anemia manifested itself in a high percentage within the
African American population since it gives its carriers a certain advantage/protection
against malaria infection

Carriers of the sickle cell anemia allele in Africa are less likely affected by malariacausing Plasmodium strains
IIII..
D
Doom
miinnaanntt ddiissoorrddeerrss

Dominant inherited human disorders are serious disorders caused by a dominant
allele. Only one (dominant) allele is required to lead to the expressed phenotype, i.e.
the human health- or wellbeing-affecting disorder
 e.g. extra or webbed fingers or toes are inherited in a
dominant way

Examples of prominent dominant disorders in humans are:
11.. A
Acchhoonnddrrooppllaassiiaa
In this very rare human genetic heterozygote individuals with the defect allele have
shortened arms and legs.
The homozygous dominant genotype leads to premature death of the embryo already
before birth.
It is very rare, since 99.99% of the human population is homozygous for the ‘normal’,
recessive allele.
Because an allele is dominant does not necessarily mean that it is
more common in a population than the recessive allele.
26
SAN DIEGO MESA COLLEGE
General Biology (BIO107)
LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
2. Familial polydactyly
In this dominant inherited human disorder, individuals are born with extra fingers or
toes. It is due to an allele dominant to the recessive allele for five digits per appendage.
However, the recessive allele is far more prevalent than the dominant allele in the
population.
399 individuals out of 400 have five digits per appendage.
3. Alzheimer’s disease (AD)
This dominant inherited neurodegenrative disorder was diagnosed in the former US
president Ronald Reagan.
It leads to mental deterioration and progressive memory loss in affected humans.
It is a late onset disorder which usually strikes late in life.
The cause and the incidence is not known

Dominant in the genetic sense, does not imply that a dominant allele is somehow
better than the corresponding recessive allele nor does it mean that a dominant
allele is more frequent in a population
Dominant … recessive tells only about the destiny of the allele and its genes within the
cells of an organism

Lethal dominant alleles are much less common than lethal recessive alleles. This is
explained by the fact that a lethal dominant allele cannot be carried by a
heterozygous individual for a long time and usually not long enough to reach the
reproductive age which would allow the passing on of the “defective allele”.
 while on the other hand, a lethal recessive allele can be carried by
many heterozygous members of a population without affecting
themselves in a serious way
4. Retinoblastoma
A hereditary form of juvenile eye cancer which is inherited in a dominant fashion.
Affected human individuals develop retinopathies and retinal cancer very early in
their child hood.
27
SAN DIEGO MESA COLLEGE
General Biology (BIO107)
LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
5. Familial (hereditary) forms of breast cancer
A hereditary form of cancer which is caused by a short deletion of the BRCA1 gene.
The BRCA gene codes for a protein which is important for DNA repair and also
plays a role in the regulation of the cell cycle.
This trait is inherited in a dominant fashion, since the presence of only one allele, i.e.
the mutated b allele, is sufficient to lead to the development of either breast or
ovarian cancers in affected females.
Pedigree of a family with hereditary form of breast & ovarian cancer
I.
2
2 Ov 59 3
.
II.
2 72
III.
1 46
3
2
4
Ov 45
Ov 40
5
Br 37
Ov 42
4 Ov 58
3
5
6
Br 54 39
?
III-
II-2
I-2 III-2 II-3 III-3 I-4
II-4
I-5
III-5 III-6
x fragment
Δx fragment
RFLP analysis/Southern Blotting
z fragment
Genotype
BB Bb bb bb BB BB Bb bb Bb Bb
z
y
DNA fragment
z
y – 40bp
*
Normal BRCA-1 gene
(B- allele)
Mutant BRCA-1 gene
(due to 40 bp deletion)
(b- allele)
28
SAN DIEGO MESA COLLEGE
General Biology (BIO107)
LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
D
Diiaaggnnoossiiss ooff hhuum
maann ggeenneettiicc ddiissoorrddeerrss
Many genetic disorders can be detected before birth by fetal testing with the help of
different clinical procedures and modern molecular biological techniques, such as
11.. A
Am
mnniioocceenntteessiiss
 is done between the 14th and 16th week of pregnancy
 a sample (2mL) of the amniotic fluid is withdrawn in a
hospital and biochemical tests as well as karyotyping is performed
 the complication rate is about 1-2%
22.. C
Chhoorriioonniicc vviilllluuss ssaam
mpplliinngg ((C
CV
VS
S))
th
 performed between the 8 and 10th week of pregnancy
 a small amount of embryonic tissue, the so-called
chorionic villi, are taken from the placenta for testing
 this procedure is faster due to the rapid growth of the embryonic cells of the
villi
3. U
Ullttrraassoouunndd iim
maaggiinngg
 sonic waves are used to check for eventual anatomical deformations or simply
to examine the position of the fetus within the womb.
44.. M
Moolleeccuullaarr bbiioollooggiiccaall tteecchhnniiqquueess,, ee..gg.. P
PC
CR
R aanndd R
RFFLLP
P
 the DNA-based methods are more and more used in clinical analysis for the
detection of DNA mutations, such as deletions, translocations and insertions,
which may be the cause for a given hereditary disorder

All these different medical methods are usually reserved for situations in which the
possibility of genetic disorders is significantly increased such as:
1. in the case of 35 year old or older women with their first pregnancy, or
2. in couples with a family history for a certain hereditary disorder
While some diseases are inherited in a simple dominant-recessive Mendelian fashion
due to alleles at a single locus, many other disorders have a multifactorial basis.
These have a genetic component plus a significant environmental influence.
Multifactorial disorders include:
1. Heart disease
2. Diabetes
3. Cancer
4. Alcoholism
5. Certain mental illnesses, such a schizophrenia and manic-depressive
disorder
The genetic component is typically polygenic.
29
SAN DIEGO MESA COLLEGE
General Biology (BIO107)
LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
Sex-Linked (or X-linked) Inheritance

In sexually reproducing organisms, not all genes or alleles coding for heritable traits
are located on autosomes. The genes for many traits are found located on the socalled sex- or gender chromosomes.

Many traits have been found to be located only on the X chromosome but not on
the Y chromosome; this is why these traits are inherited in a unique fashion different
to traits located on autosomes.
X-chromosomal inheritance pattern of Hemophilia
reflected in the family pedigree of the European high aristocracy
Queen Victoria
of England
Prince Albert von
Sachsen-CoburgGotha
carrier
Prinz
Heinrich
v. Battenberg
Alice
Heinrich
v. Preussen
Irene
Alexandra
Frederick
Waldemar
Heinrich
Leopold Beatrice
Duke of Albany
Ludwig v. Hessen
Czar Nikolaus
II
Alexis
Alice
Ruprecht
Alfonso
of Spain
Gonzalo

The study of inheritance of genes located on sex chromosomes was pioneered by
T. H. Morgan and his students at the beginning of the 20th century

Even though Morgan studied fruit flies (Drosophila), we know today, that the same
genetic principles of sex-linked or X-linked inheritance apply to humans as well.

Since males and females of higher biological organisms differ in their sex
chromosomes, inheritance patterns for X-chromosome linked genes vary between
the sexes.
30
SAN DIEGO MESA COLLEGE
General Biology (BIO107)
LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
Human Chromosomes & X-linked Inheritance
22 pairs of homologous chromosomes in humans
1
11
2
12
3
13
4
14
15
5
6
16
17
7
18
8
9
20 21
19
1
22
Autosomes
Male
Female
or
X Y
X X
Sex or gender chromosomes
X-linked genes
Male-making genes
e.g. SRY gene
Homologous sections
X
Y
Chromosome
©ESchmid/MesaCollege2001
31
SAN DIEGO MESA COLLEGE
General Biology (BIO107)
LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
S
Seexx-- oorr X
X--lliinnkkeedd IInnhheerriittaannccee iinn D
Drroossoopphhiillaa
 In the common fruit fly Drosophila, the alleles for eye color and for body color are
located on the X chromosome, but are not found on the Y chromosome. The eye
color allele is X-linked.

W ) is dominant inherited, the white eye color (w
w ) is the
The red eye color allele (W
recessive allele. The tan body color (y+) is dominant over the yellow body color (y).
Geneticists say, that red eyes are dominant, X-linked, while white eyes are X-linked,
recessive inherited.
P
Phheennoottyyppee aanndd ggeennoottyyppee ooff tthhee sseexx--lliinnkkeedd ttrraaiitt ““eeyyee ccoolloorr”” iinn D
Drroossoopphhiillaa
P
Paarreennttss
((== P
P ggeenneerraattiioonn))
Phenotype
Genotype
Gender chromosome
 The female parent is homozygous; the red-eyed male parent is a hemizygous
ooffffsspprriinngg
((FF11 ggeenneerraattiioonn))
Genotypes
Phenotypes
32
SAN DIEGO MESA COLLEGE
General Biology (BIO107)

LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
All female offspring are rreedd--eeyyeedd heterozygous; all male offspring are w
whhiittee--eeyyeedd and
hemizygous
X
X--lliinnkkeedd iinnhheerriittaannccee iinn hhuum
maannss

Certain traits and disorders in humans, e.g. a disease called Hemophilia, are also
inherited in a X-linked manner.
 the disease Hemophilia is due to a mutation of a gene coding for a blood
cogulation factor, which is located on the X-chromosome
 the mutated coagulation factor protein is defect and not able to
successfully contribute to blood clot formation after a wound appeared
 as a consequence, the affected individual is permanently bleeding
 therefore hemophilic persons are often referred to as “bleeders”

Hemophilia is a hereditary blood coagulation disorder, which is caused by a mutation
of one of the genes which code for one of the many blood coagulation factors and which
are responsible for normal blood clotting, e.g. after trauma or injury.

The X-linked inherited disorder affects mostly males, which show a dangerously
delayed clotting of their blood and abnormal bleeding.

Red-green color blindness and X-linked (Duchenne-type) Muscular Dystrophy are
two other prominent examples of X-chromosome-linked trait inherited in humans. The
allele which causes red-green color blindness is recessively inherited

A human female who is homozygous for the recessive red-green color blindness allele
and a hemizygous male are not able to discriminate between the red and green color

Can you …. tell me which of the following words is
rreedd and which one is ggrreeeenn?
33
SAN DIEGO MESA COLLEGE
General Biology (BIO107)
LIFE SCIENCES DEPARTMENT
Instructor: Elmar Schmid, Ph.D.
R
Reessuullttss ooff m
maattiinngg bbeettw
weeeenn aa nnoorrm
maall ((nnoonn--ccaarrrriieerr))
ffeem
a
l
e
a
n
d
a
h
e
m
o
p
h
i
l
i
male and a hemophilicc m
maallee

all of the daughters inherit an X chromosome with the mutation from their father, and will
be carriers; all the sons inherit a normal X chromosome from their mother.


34