Title
Capt. Piyapol Anubuddhangkura
B.S. (1 st class honors cum gold medal) in Genetics,
M.S. in Biophysics
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

• Heredity , the transmission of genetic information from parent to offspring, generally follows predictable patterns in organisms.
• Genetics , the science of heredity, studies both genetic similarities and genetic variation , the differences, between parents and offspring or among individuals of a population.

• The science of genetics explains the stability of inheritance and also variations between offspring from one generation to the next.
• An understanding of inheritance patterns has always been important to agriculture, animal husbandry, and medicine.

• The Blending Concept of
Inheritance 

• In blending inheritance , male and female gametes supposedly contained fluids that blended together during reproduction to produce hybrid offspring with features intermediate between those of the mother and father.
• The fact that dominance can occur was not consistent with the notion of blending inheritance.

• The Blending Concept of
Inheritance 
• However, the theory did not always explain observed inheritance patterns. 
– Charles Darwin: If populations contained only intermediate individuals and normally lacked variations, how could diverse forms evolve?
• Mendel’s Particulate Theory of Inheritance

• He was one of the first scientists to apply mathematics to biology .
• He was a careful, deliberate scientist who followed the scientific method very closely and kept very detailed, accurate records.
• The very reason his theory is termed “ particulate ” theory is that it is based on the existence of minute particles or hereditary units we now called genes.
• Mendel chose the garden pea, Pisum sativum, as his experimental material.

Fig. 11.2a
• Why garden pea?
– Easy to cultivate
– Short generation time
– Could be cross-pollinated
– Many varieties available

Fig. 11.2b

• In contrast to his predecessors, Mendel studied the inheritance of relatively simple and discrete traits that were not subjective and were easy to observe.
• In his crosses, Mendel observed either dominant or recessive characteristics but no intermediate ones.

Fig. 11.2

• Law of Segregation
– Mendel chose varieties that differed in only one trait.
– If the blending theory of inheritance were correct, the cross should yield offspring with an intermediate appearance compared to the parents. 
– He performed reciprocal crosses. 
– When Mendel allowed the F of the F
2
1 plants to self-pollinate, ¾ generation were tall and ¼ were short, a 3:1 ratio.

Fig. 11.3
Monohybrid cross : parents are hybrids in one way.
Today, we know that the expected phenotypic results of a monohybrid cross are always
3:1.
Therefore, the F
1 plants were able to pass on a factor for shortness.

• Widow’s Peak and Straight Hairline
– W = Widow’s peak (dominant allele)
– w = Straight hairline (recessive allele)

• The law of segregation states the following:
– Each individual has two factors for each trait.
– The factors segregate during the formation of gametes.
– Each gamete contains only one factor from each pair of factors.
– Fertilization gives each new individual two factors for each trait.

• In Mendel’s cross, the original parents (P generation) were true-breeding; therefore, the tall plants had two alleles for tallness (TT), and the short plants had two alleles for shortness (tt).
• When an organism has two identical alleles we say it is homozygous .
• After cross-pollination, all the individuals of the resulting F
1 generation had one allele for tallness and one for shortness (Tt). The allele expressed is the dominant allele.
• When an organism has two different alleles at a gene locus, we say that it is heterozygous .

• Mendel’s Cross as Viewed by Classical Genetics
– Stem length in peas is controlled by a single gene.
– This gene occurs on a homologous pair of chromosomes at a particular location is called the gene locus .

– Alternative versions of a gene are called alleles .

– The dominant allele is so named because of its ability to mask the expression of the recessive allele .

Fig. 11.4

The process of meiosis gives an explanation for Mendel’s law of segregation, and why only one allele for each trait is in a gamete.

• Genotype Versus Phenotype
– The word genotype refers to the alleles an individual receives at fertilization.
• TT = homozygous dominant
• tt = homozygous recessive
• Tt = heterozygous
– The word phenotype refers to the physical appearance of the individual.
– The phenotype is dependent upon the genotype of the individual.

Table 11.1

Fig. 11.5
The law of independent assortment applies only to alleles on different chromosomes.
The F
1 plants showed both dominant characteristics.
The F
1 cross is known as a dihybrid cross .

• The law of independent assortment states the following:
– Each pair of factors segregates (assorts) independently of the other pairs.
– All possible combinations of factors can occur in the gametes.

Fig. 12A

• In 1902, American biologist Walter Sutton and German biologist Theodor Boveri independently pointed out the connection between Mendel’s segregation of alleles and separation of homologous chromosomes during meiosis. This connection developed into the chromosome theory of inheritance , which stated that inheritance can be explained by assuming that genes are linearly arranged in specific locations along the chromosomes.

• Mendel’s Laws of Probability
– The Punnett square allows us to easily calculate the chances, or the probability, of genotypes and phenotypes among the offspring. 
– The product rule of probability tells us that we have to multiply the chances of independent events to get the answer.
– The sum rule of probability tells us that when the same event can occur in more than one way, we can add the results.
– Another useful concept is the statement that “ chance has no memory .”

Fig. 11.6

– The probable results of 3:1 or 9:3:3:1 tell us the probable phenotypic ratio among the offspring, but not the chances for each possible phenotype.

• How could we know that an F
1 cross is a heterozygous? plant of a one-trait
• How could we know that a tall pea plant is a homozygous or heterozygous?
• Testcrosses
– To confirm that the F
1 plant of his one-trait crosses were heterozygous , Mendel crossed his F
1 generation plants with true-breeding, short (homozygous recessive) plants.
– One-Trait Testcross
– Two-Trait Testcross

Fig. 11.7
Mendel reasoned that half the offspring should be tall and half should be short, producing a 1:1 phenotypic ratio.
Today, a one-trait testcross is used to determine if an individual with the dominant phenotype is homozygous dominant (TT) or heterozygous
(Tt).

Page 197
Homozygous recessive for both traits
L = long wings
G = gray bodies l g
= vestigial (short) wings
= black bodies

• If the test fly is homozygous dominant for both traits with the genotype LLGG, it will form only one gamete: LG.
 All the offspring from the proposed cross will have long wings and a gray body.
• If the test fly is heterozygous for both traits with the genotype LlGg, it will form four different types of gametes: LG, Lg, lG, lg.


Page 197
The expected phenotypic ratio for this type of two-trait cross
(heterozygous for two traits × recessive for both traits) is always 1:1:1:1.

• Backcross
– Backcross is the mating of a hybrid organism (offspring of genetically unlike parents) with one of its parents or with an organism genetically similar to the parent. The backcross is useful in genetics studies for isolating
(separating out) certain characteristics in a related group of animals or plants.

Pedigree analysis most often identifies three modes of singlelocus inheritance: autosomal dominant, autosomal recessive, and X-linked recessive.

• Mendel’s Laws and Human Genetic Disorders
– These traits are controlled by a single pair of alleles on the autosomal chromosomes.
• Autosomal Patterns of Inheritance
– When a genetic disorder is autosomal dominant , the normal allele (a) is recessive, and an individual with the alleles AA or Aa has the disorder.
– When a genetic disorder is autosomal recessive , the normal allele (A) is dominant, and only individuals with the alleles aa have the disorder.

Page 197
Which pattern of inheritance do you suppose to represent an autosomal dominant/recessive characteristic?

Fig. 11.8
significantly heterozygous copies of a that is affected.

Fig. 11.9
This person is heterozygous because he has a child that is unaffected.

• Autosomal Recessive Disorders
– Methemoglobinemia
• Individuals with methemoglobinemia are unable to clear the abnormal blue protein from their blood, causing their skin to appear bluish-purple in color.
• Enzyme tests indicated that the blue Fugates lacked the enzyme diaphorase, coded by a gene on chromosome 22. The enzyme normally converts methemoglobin back to hemoglobin.
• Methemoglobin is hemoglobin that has been oxidized from the ferrous (Fe++) to the ferric (Fe+++) state, thus unable to bind oxygen. The NADH-methemoglobin reductase enzyme reduces methemoglobin to hemoglobin. Methemoglobinemia results from either inadequate enzyme activity or too much methemoglobin production.

– Cystic Fibrosis
• CF patients exhibit a number of characteristic symptoms, the most obvious being extremely salty sweat.
• In children with CF, the mucus in the bronchial tubes and pancreatic ducts is particularly thick and viscous, interfering with the function of the lungs and pancreas.
• CF is caused by a defective chloride ion channel that is encoded by the CFTR allele on chromosome 7.
• It is hoped that other novel treatments, such as gene therapy , may be able to correct the defect by placing a normal copy of the gene in patients to replace the faulty ones.
• To explain the persistence of the mutated CFTR allele in a population, it has been suggested that those heterozygous for
CF are less likely to die from potentially fatal diseases, such as cholera.

– Niemann-Pick Disease
• In infants, a persistent jaundice, feeding difficulties, an enlarged abdomen, and pronounced mental retardation may signal to a medical professional that the child has Niemann-
Pick disease.
• Type A and B forms of Niemann-Pick disease are caused by defective versions of the same gene located on chromosome 11.
This gene codes for acid sphingomyelinase, an enzyme that normally breaks down a lipid called sphingomyelin.
• Affected individuals accumulate lipid droplets within cells of the liver, lymph nodes, and spleen.
• The abnormal accumulation of lipids causes enlargement of the abdomen.

• Autosomal Dominant Disorders
– Osteogenesis Imperfecta
• Osteogenesis imperfecta is an autosomal dominant genetic disorder that results in weakened, brittle bones.
• Osteogenesis imperfecta leads to a defective collagen I that causes the bones to be brittle and weak.
• Collagen has many roles, including providing strength and rigidity to bone and forming of framework for most of the body’s tissues.
• Because the mutant collagen can cause structural defects even when combined with normal collagen I, osteogenesis imperfecta is generally considered to be dominant.
• Currently, the disorder is treatable with a number of drugs that help to increase bone mass, but these drugs must be taken longterm.

Osteogenesis imperfecta Type V Adult X Ray
Ramana Murthy Reddicharla

Skull of an Egyptian child of the 22nd dynasty ( 945-716 BCE ) who suffered from osteogenesis imperfecta , a .
k .
a . " brittle bone syndrome " ( British Museum )

– Hereditary Spherocytosis
• The abnormal spherocytosis protein is unable to perform its usual function, causing the affected person’s red blood cell to adopt a spherical shape.
• Hereditary spherocytosis exhibits incomplete penetrance, so not all individuals who inherit the mutant allele will exhibit the trait.

– Huntington Disease
• Huntington disease is a devastating neurological disease caused by the inheritance of a single dominant allele.

A large number of individuals either had a sequence designated as
J, K, or L.
Only the sequence of bases designated as L appears in all the individuals with Huntington disease.

huMan TraiTs
• Follow Mendelian laws
– Albinism (autosomal, recessive), webbed fingers (autosomal, dominant), short-limbed dwarfism (autosomal, dominant)

• Multiple Allelic Traits
– If three or more alleles for a given locus exist within the population, we say that locus has multiple alleles .
– Some alleles can be identified by the action of certain enzyme or by some other biochemical feature but do not produce an obvious phenotype.
– ABO blood type
• I A = A antigen (a glycoprotein) on red blood cells
• I B = B antigen on red blood cells
• i = Neither A nor B antigen on red blood cells
– The possible phenotypes and genotypes for blood type are as follows:
Phenotype
A
B
AB
O
Genotype
I A I A , I A i
I B I B , I B i
I A I B ii

– The inheritance of the ABO blood group in humans is an example of codominance .
– Reproduction between a heterozygote with type A blood and a heterozygote with type B blood can result in any one of the four blood types.
 For this reason, DNA fingerprinting is now used to identify the parents of an individual instead of blood type.

C > c ch > c h > c

• In rabbits, four alleles occur at the locus for coat color. A C allele causes a fully colored dark gray coat.
The homozygous recessive genotype, cc , causes albino (white) coat color. These are two additional allelic variants of the same locus, c ch and c h .
• An individual with the genotype c ch c ch has the chinchilla pattern, in which the entire body has a light, silvery gray color.
• The genotype c h c h causes the Himalayan pattern, in which the body is white but the tips of the ears, nose, tail, and legs are colored, like the color pattern of a
Siamese cat.

• Incomplete Dominance and Incomplete Penetrance
– Incomplete dominance is exhibited when the heterozygote has an intermediate phenotype between that of either homozygote.
– An example of four-o’clock (Mirabilis jalapa) 
• The reappearance of the three phenotypes in this generation makes it clear that we are still dealing with a single pair of alleles.
• A double dose of pigment results in red flowers; a single dose of pigment results in pink flowers; and because white flowers produce no pigment, the flowers are white.

Fig. 11.13
When pink four-o’clocks selfpollinate, the results show three phenotypes. This is only possible if the pink parents had an allele for red pigment (R
1
) and an allele for no pigment
(R
2
). Note that alleles involved in incomplete dominance are both given a capital letter.

• In complete dominance is not unique to four o’clock, and additional examples of incomplete dominance are known in both plants and animals.
• For example, true-breeding white chickens and truebreeding black chickens produce bluish gray offspring, known as Andalusian blues, when crossed.

Notice that in these crosses, the genotypic and phenotypic ratios are identical.

– In some cases, a dominant allele may not always lead to the dominant phenotype in heterozygote, even when the alleles show a true dominant/recessive relationship. The dominant allele in this case does not always determine the phenotype of the individual, so we describe these traits as showing incomplete penetrance .
• Polydactyly is inherited in an autosomal dominant manner; however, not all individuals who inherit the dominant allele will exhibit the trait.
• Human Examples of Incomplete Dominance
– Familial hypercholesterolemia (FH)
– Cystic fibrosis

• Pleiotropic Effects
– Pleiotropy occurs when a single mutant gene affects two or more distinct and seemingly unrelated traits.
• Persons with Marfan syndrome have disproportionately long arms, legs, hands, and feet; a weaken aorta; poor eyesight; and other characteristics. 
 Due to the production of abnormal connective tissue.
• Cystic fibrosis
• Porphyria
• Sickle-cell disease  
– Although sickle-cell disease is a devastating disorder, it provides heterozygous individuals with a survival advantage (resistant to the protozoan parasite that causes malaria).
– Most cases of pleiotropy can be traced to a single fundamental cause. For example, a defective enzyme may affect the functioning of many types of cells.

Page 203

• Polygenic Inheritance
– Polygenic inheritance occurs when a trait is governed by two or more sets of alleles. The individual has a copy of all allelic pairs, possibly located on many different pairs of chromosomes.
– Each dominant allele has a quantitative effect on the phenotype, and these effects are additive. Therefore, a population is expected to exhibit continuous phenotypic variations.

– Multifactorial traits are controlled by polygenes subject to environmental influences.  
• Human Examples of Multifactorial Inheritance
– Human skin color and height are examples of polygenic traits affected by the environment.
– Eye color is also a polygenic trait.

Fig. 11.15
In polygenic inheritance, a number of pairs of genes control the trait.
Black dots and intensity of blue shading stand for the number of dominant alleles.
Orange shading shows the degree of environmental influences.

The coats of Siamese cats and Himalayan rabbits have darker tipped ears, nose, paws, etc. due to the enzyme encoded by an allele which is only active at the extremities at low temperatures.

– Many human disorders are most likely due to the combined action of many genes plus environmental influences.
– In recent years, reports have surfaced that all sorts of behavioral traits, such as alcoholism, phobias, and even suicide, can be associated with particular genes.
Cardiovascular disease is more prevalent among those whose biological or adoptive parents have cardiovascular disease.
Can you suggest environmental reasons for this correlation?

• Sex Determination

Birds, amphibians ZZ (male) ZW (female)
Grasshoppers, crickets, cockroaches XO XX
Bees, ants, wasps n 2n

• X-Linked Inheritance
– The X and Y chromosomes in mammals determine the gender of the individual. In particular, if the Y chromosome contains an SRY gene, the embryo becomes a male.
– The term X-linked is used for genes that have nothing to do with gender, and yet they are carried on the X chromosome.
– Discovered in the early 1900s by a group at Columbia
University, headed by Thomas Hunt Morgan.
– Fruit flies, Drosophila melanogaster, have the same sex chromosome pattern as humans.

• Morgan’s Experiment
– Morgan took a newly discovered mutant male with white eyes and crossed it with a red-eyed female.

Page 205
The expected 3 red-eyed : 1 white-eyed
These results support the chromosome theory of inheritance by showing that the behavior of a specific allele corresponds exactly with that of a specific chromosome—the X chromosome in
Drosophila.

• Solving X-Linked Genetic Problems 
– The allele key for an X-linked gene shows an allele attached to the X:
X R
X r
=
= red eyes white eyes
– The possible genotypes in both males and females are as follows:
X R X R =
X R X r =
X r X r = red-eyed female red-eyed female white-eyed female
X R Y =
X r Y = red-eyed male white-eyed male

Fig. 11.16
Males are considered hemizygous for X-linked traits, because a male only posseses one allele for the trait.
The fruit fly has XX females and XY males, but the Y does not determine maleness; a fruit fly with only one X chromosome and no
Y chromosome has a male phenotype.
Males cannot be carriers for X-linked traits.

• Human X-Linked Disorders
– Color Blindness
• The allele for the bluesensitive protein is autosomal, but the alleles for the red- and green-sensitive pigments are on the X chromosome.

– Menkes Syndrome
• The symptoms of Menkes syndrome are due to accumulation of copper in some parts of the body, and the lack of the metal in other parts.

– Duchenne Muscular Dystrophy
• The absence of a protein called dystrophin causes the disorder.
• A test is now available to detect carriers of Duchenne muscular dystrophy.

– Adrenoleukodystrophy (ALD)
• ALD is an X-linked recessive disorder due to the failure of a carrier protein to move either an enzyme or very long chain fatty acid into peroxisomes. As a result, these fatty acids are not broken down, and they accumulate inside the cell and the result is severe nervous system damage.
• The disease was made famous by the 1992 movie Lorenzo’s
Oil.

– Hemophilia
• There are two common types of hemophilia: Hemophilia A is due to the absence or minimal presence of a clotting factor known as factor VIII, and hemophilia B is due to the absence of clotting factor IX.

• Hemophilia

• Human X-linked dominant trait
– Congenital generalize hypertrichosis