Unit 12: Inheritance of

Human Traits
Dr. K.K.Therisa
Assistant Professor
Department of Zoology
DCT’s Dhempe college of Arts and Science, Miramar.
Preview: (05)

• Human karyotype
• Pedigree analysis
• Inheritance of human traits: Brown eyes, Polydactyly, Diabetes
insipidus, Sickle cell anaemia, PKU
• Eugenics and Genetic counselling
 Human karyotype

• Karyotyping is the process by which photographs of chromosomes are taken in

order to determine the chromosome complement of an individual, including the
number of chromosomes and any abnormalities.

• The study of whole sets of chromosomes is sometimes known as karyology. The

chromosomes are depicted (by rearranging a photomicrograph) in a standard
format known as a karyogram or idiogram: in pairs, ordered by size and position
of centromere for chromosomes of the same size.
• Tjio and Levan in 1956 cultured somatic cells from fibroblasts of human embryos and
counted the human chromosome number as 46.
• The representation of the entire chromosome set as a series of banded chromosomes is
called a Karyogram.
• For Karyotyping of Human chromosomes, venous blood is taken and blood leucocytes are
stimulated to divide by mitosis, in vitro, by the addition of Phytohaemagglutinin.
• Colchicine is added to arrest cell division at metaphase stage.
• It is further treated with hypotonic saline solution which results in swelling of cells and
dispersal and better clarity of chromosomes for counting and morphological study.
• There after, the material is stained with Giemsa technique, to demonstrate the banding
patterns of chromosomes.
• Finally, suitable metaphase spread is photographed through a high power microscope.
• The individual chromosomes are cut out from the photograph.
• The chromosomes are then arranged in an orderly fashion in homologous pairs, to
produce a standard arrangement, the Karyotype.
• To characterize a chromosome in the karyotype, the following parameters are used:
1. Shape of chromosome
2. Length of chromosome
3. Centromeric Index: is expressed in the form of ratio of the short arm length to the total
chromosome length.
4. Proportion of the arms: i.e. it is the ratio between the long arm and short arm of the
chromosome.
Chromosome Banding Technique:
• Chromosome banding permits structural definitions and differentiation of chromosomes.
• A variety of treatments involving denaturation and/or enzymatic digestion of chromatin, followed by
incorporation of a DNA-specific dye/stain, can cause mitotic chromosomes of complex organisms.
• Eg: Human beings, to appear as a series of transverse alternating light and dark staining bands.
• Banding reflects variations in the longitudinal structure of chromatids; each chromatid may be viewed
as a series of stacked discs where each disc differs from that of its nearer neighbours in base
composition, time of replication, chromatin conformation and also in the density of genes and
repetitive sequences.
Down Syndrome
• Down syndrome was one of the first reported chromosomal abnormalities in humans.
• It was described as Mongolian Idiocy by John Langdon Down in 1866.
• It wasn’t until 1959 that it was shown to be caused by the presence of an extra chromosome 21,
resulting in an increase of number of chromosomes to 47 (karyotype 47, XX / XY, +21).
• Thus, this disorder is also known as trisomy 21 or Down syndrome.
• With an incidence of 1 in 800 live births, this is one of the common trisomies seen in humans.
• This incidence increases to 1 in 350 when the woman conceives beyond 35 years of age and to 1 in 25
when she conceives beyond 45 years.
• Down syndrome is caused by trisomy 21 in almost 90% of the cases. 6% of the cases are also shown
to be caused by a translocation rather than a numerical change and the other 4 % are known to be
caused by mosaicism.
• There are many phenotypic manifestations that are typical in patients of this syndrome.
• However, as in other syndromes, not all affected individuals show all the symptoms.
• Any single individual usually expresses only a subset of the manifestations. Some of the most common
are:
 Flat face, round head, and typical epicanthic fold of the eyes
 Short, broad hands
 Mental retardation
 Hypotonia – poor muscle tone
 Short stature
 Protruding furrowed tongue
 Mild to moderate developmental disabilities
 Typical dermatoglyphic patterns (palm and fingerprint patterns)
Turner Syndrome

• This syndrome is characterized by the partial or complete absence of one of the X

chromosomes in female.
• This results in a reduction of the total number of chromosomes to 45 (karyotype – 45, X).
• Thus, this syndrome is also called Monosomy X.
• Its first description as a syndrome was by Henry Turner in 1938.
• Later, in 1954, the absence of barr body (inactivated X-chromosome seen in buccal cells)
and presence of only one X chromosome was noted.
• As in Down syndrome, monosomy of X is not the only cause of this syndrome.
• Mosaicism, deletions and isochromosome have also been shown to cause this condition.
TURNER SYNDROME
• It is well known that, of the two X chromosomes in females, one is inactivated throughout
her lifetime.
• If normal females have only one active X chromosome, then why should the loss of one X
chromosome cause abnormal phenotype? The answer lies in the fact that although we
speak of inactivated X chromosome, not all genes on that chromosome are being
inactivated.
• There is a small subset of genes on the X chromosomes that are required to be expressed
by both chromosomes for normal female development.
• Thus, individuals who lack one X chromosome fail to develop normal female character.
• Some of the commonly seen manifestations of Turner syndrome are:
 Primary hypogonadism – poor ovary development
 Short stature
 Minimal breast development
 Broad shield-like chest with widely spaced nipples
 Absence of menstrual periods
 Absence of secondary sexual characteristics
 Horseshoe-shaped kidney
 Inability to produce gametes - sterility
Klinefelter Syndrome

• The presence of an additional X chromosome in males causes abnormal sexual development and is
described as Klinefelter syndrome.
• This set of characteristics was first described by Harry Klinefelter in 1942.
• In 1959 it was shown to be due to the presence of an additional X chromosome in males by the presence
of barr
bodies in these males (normal males do not show barr body).
• The additional X chromosome results in an increase in the total number of chromosomes to 47 (karyotype
47, XXY).
• It has an overall incidence of 1 in 1000 live male births.
• While most patients show the XXY condition, individuals showing variations like XXXY or XXYY have
also been reported.
Klinefelter Syndrome
• The additional X chromosome arises due to non-disjunction during meiosis.
• Due to this, the gamete contains two X chromosomes rather than one.
• When such an egg containing XX is fertilized by sperm containing Y, an XXY zygote is formed that develops into
a Klinefelter male.
• The extra X chromosome may be either of maternal or paternal origin, but it is more often to be of maternal origin.
• Individuals with this syndrome show hypogonadism and reduced fertility.
• These males do no develop masculine secondary sexual characteristics and show female type characteristics.
• Some of the clinical manifestations include:
 Primary male hypogonadism
 Reduced facial, body and pubic hair
 Small and soft testes
 Slight learning difficulties
 Increased breast tissue – gynacomastia
 Long limb bones and lanky body
 Azoospermia – absence of sperm production leading to infertility
PEDIGREE ANALYSIS
• Pedigrees are used to analyze the pattern of inheritance of a particular trait throughout a family.
• Pedigrees show the presence or absence of a trait as it relates to the relationship among parents, offspring,
and siblings.
• Pedigrees represent family members and relationships using standardized symbols.
• By analyzing a pedigree, we can determine genotypes, identify phenotypes, and predict how a trait will be
passed on in the future.
• The information from a pedigree makes it possible to determine how certain alleles are inherited: whether
they are dominant, recessive, autosomal, or sex-linked.
• Determine whether the trait is dominant or recessive. If the trait is dominant, one of the
parents must have the trait. Dominant traits will not skip a generation. If the trait is recessive, neither
parent is required to have the trait since they can be heterozygous.
• Determine if the chart shows an autosomal or sex-linked (usually X-linked) trait. For example, in X-linked
recessive traits, males are much more commonly affected than females. In autosomal traits, both males and
females are equally likely to be affected (usually in equal proportions).
 X-linked recessive trait
Autosomal dominant trait
 Common mistakes and misconceptions
• The presence of many affected individuals in a family does not always mean that the trait is
dominant. The terms dominant and recessive refer to the way that a trait is expressed, not by
how often it shows up in a family. In fact, although it is uncommon, a trait may be recessive but
still show up in all generations of a pedigree.

• You may not always be able to determine the genotype of an individual based on a
pedigree. Sometimes an individual can either be homozygous dominant or heterozygous for a
trait. Often, we can use the relationships between an individual and their parents, siblings, and
offspring to determine genotypes. However, not all carriers are always explicitly indicated in a
pedigree, and it may not be possible to determine based on the information provided.
 Brown Eyes
• A person’s eye color depends on how much of a pigment called melanin is stored in the front layers of the
iris, the structure surrounding the pupil.

• Specialized cells called melanocytes produce the melanin, which is stored in intracellular compartment
called melanosomes.

• People have roughly the same number of melanocytes, but the amount of melanin within melanosomes
and the number of melanosomes within melanocytes both vary.

• Eye color ranges depending on how much melanin is stored in these compartments.

• In people with blue eyes a minimal amount of melanin is found within a small number of melanosomes.

• People with green eyes have a moderate amount of melanin and moderate number of melanosomes,
while people with brown eyes have high amount of melanin stored within many melanosomes.
https://d2jx2rerrg6sh3.cloudfront.net/image-handler/ts/20170831014040/ri/673/picture/2017/8/shutterstock_109564340.jpg
• The amount of melanin stored is determined by genes that are involved in the production, transport and storage of
melanin.

• To date, researchers have discovered more than 150 genes that influence eye color, a number of which have been
discovered through studies of genetic disorders.

• One region of chromosome 15 contains two genes located near to each other that play major roles in determining eye
color. One gene, called OCA2, codes for a protein called P protein, which is involved in melanosome maturation and
affects the amount and quality of melanin stored in the iris.

• A number of genetic variations (polymorphisms) in this gene reduce how much P protein is produced and result in a
lighter eye color.

• The other main gene involved is called HERC2. Intron 86 on this gene controls the expression of OCA2, activating it or
deactivating it as required.

• At least one polymorphism in this intron reduces the expression and activity of OCA2,which reduces how much P
protein is produced.

• A number of other genes play smaller roles in eye color. The roles of the genes ASIP, IRF4, SLC24A4, SLC24A5, SLC45A2,
TPCN2, TYR, and TYRP1 are thought to combine with those of OCA2 and HERC2.
• Due to the number of genes involved in eye color, the inheritance pattern is complex.
• Although a child’s eye color can generally be predicted by looking at the color of the parents’ eyes, the
polymorphisms that can arise mean a child may well have an unexpected eye color.
• A child’s eye color depends on the pairing of genes passed on from each parent, which is thought to involve
at least three gene pairs.
• The allele for brown eyes is the most dominant allele and is always dominant over the other two alleles and
the allele for green eyes is always dominant over the allele for blue eyes, which is always recessive.
• This means parents who happen to have the same eye color can still produce a different eye color in their
child.
• For example, if two parents with brown eyes each passed on a pair of blue alleles to their offspring, then the
child would be born with blue eyes.
• However, if one of the parents passed on a green allele, then the child would have green eyes and if a
brown allele was present, then the child would have brown eyes irrespective of what the other three alleles
were.
Polydactyly
• More than five fingers or toes or both. Inherited
as an autosomal dominant phenotype.
• Known as hyperdactyly, is an anomaly
in humans and animals resulting
in supernumerary fingers and/or toes.
• This condition is commonly inherited, and it may
be part of a syndrome, that is, a number of other
malformations that tend to appear together in
the same individual. And it can be inherited, or it
can be sporadic or non-genetic.
• It is among the most common congenital limb anomaly
observed immediately at birth, manifesting in a variety of
forms, ranging from complete or incomplete duplication of
digits.
• Its occurrence is estimated 1.6–10.7/1000 in general
population, 0.3–3.6/1000 in live births and males are often
affected twice as females.
• Phenotypically, polydactyly is an extremely heterogeneous
deformity, with high tendency for the involvement of right
hand than the left, upper limbs are more affected than the
lower and left foot more affected than the right.
• Mechanisms such as genetic and allelic heterogeneity,
epigenetic factors, associated genes, the role of
enhancers/suppressors, and different type of environmental
and developmental factors plays a very important role.
 Diabetes insipidus

Diabetes insipidus is a rare condition that causes your body to make a lot of urine that is "insipid," or colorless and
odorless. Most people urinate 1 to 2 quarts a day.

People with diabetes insipidus can pass between 3 and 20 quarts a day. It's also called central DI, pituitary DI,
hypothalamic DI, neurohypophyseal DI, or neurogenic DI.

Diabetes insipidus is a different disease from diabetes mellitus. Their names are similar, but the only things they have
in common is that they make you thirsty and make you urinate a lot.

If you have diabetes insipidus, the hormones that help your body balance liquids don’t work. Only one in every 25,000
people gets this condition.

With diabetes mellitus (often shortened to “diabetes”), your body can’t use energy from food like it should. It’s far
more common. Around 100 million Americans have type 1 or type 2 diabetes.
Symptoms of Diabetes Insipidus
•Severe thirst
•polyuria
• Bed-wetting
•Pale, colorless urine
•Dehydration
•Weakness
•Muscle pains
•Crankiness
•Extreme thirst
•Fatigue
•Feeling sluggish
•Dizziness
•Confusion
•Nausea
•Loss of consciousness
Diabetes Insipidus Causes

Body makes a hormone called vasopressin in a part of the brain called the hypothalamus. It’s stored in
the pituitary gland. Vasopressin stimulates kidneys to hold on to water, which makes urine more
concentrated. (Vasopressin is also called antidiuretic hormone or ADH.)

When one is thirsty or a little dehydrated, vasopressin levels go up. Kidneys absorb more water and put
out concentrated urine. If had enough to drink, vasopressin levels fall, and what comes out is clear and
diluted.
When body doesn’t make enough vasopressin, the condition is called central diabetes insipidus. Anyone
can get central DI, but it's not common. Only about 1 in every 25,000 people gets it.
When the kidneys don’t respond to it the way they should, the condition is called as nephrogenic
diabetes insipidus.
In either form, the result is the same that is kidneys can't keep water, so even dehydrated.
Diabetes Insipidus Risk Factors
Changes in the genes that you inherit from your parents can make you more likely to get diabetes
insipidus. This happens in 1% to 2% of cases.

Types of Diabetes Insipidus

•Central diabetes insipidus. when damage to hypothalamus or pituitary gland affects body
vasopressin level. Kidneys remove too much fluid from the body. This damage can result from:
•A tumor
•A head injury
•A blocked or bulging artery (aneurysm)
•Diseases such as Langerhans cell histiocytosis
•Infection
•Inflammation
•Surgery
•Nephrogenic diabetes insipidus. when kidneys don’t respond to vasopressin and take too much fluid from your
bloodstream. some causes include:
• A blocked urinary tract
• Chronic kidney disease
• High levels of calcium in your blood
• Low levels of potassium in your blood
• Some medications, like lithium

•Dipsogenic diabetes insipidus. This type, also known as primary polydipsia, happens when your body has trouble
controlling thirst. When you drink, the liquid lowers the amount of vasopressin that your body makes, while making
you pee more. Causes include damage to your hypothalamus or pituitary glands from:
• A tumor
• A head injury
• Infection
• Inflammation
• Surgery
•Gestational diabetes insipidus. Sometimes, a woman’s placenta -- the organ that gives oxygen and

nutrients to the baby -- makes an enzyme that breaks down vasopressin. Other pregnant women make

more prostaglandin, a hormone-like chemical that makes their kidneys less sensitive to vasopressin.

Most cases of gestational diabetes insipidus are mild and don’t cause clear symptoms. The condition

usually goes away after birth, but it might come back in another pregnancy.
Nephrogenic diabetes insipidus is a rare hereditary disorder, most commonly transmitted

in an X chromosome-linked recessive manner and characterized by the lack of renal

response to the action of antidiuretic hormone [Arg8]vasopressin. The vasopressin type 2

receptor (V2R) has been suggested to be the gene that causes the disease, and its role in

disease pathogenesis is supported by mutations within this gene in affected individuals.

Familial neurohypophyseal diabetes insipidus is almost always inherited in an

autosomal dominant pattern , which means one copy of the altered AVP gene in each cell

is sufficient to cause the disorder. In a few affected families, the condition has had an

autosomal recessive pattern of inheritance.

 Sickle cell anaemia

• Sickle cell anemia is a disease in which the body produces abnormally

shaped red blood cells that have a crescent or sickle shape. These cells do
not last as long as normal, round, red blood cells, which leads to anemia (low
number of red blood cells). The sickle cells also get stuck in blood vessels,
blocking blood flow.
Signs and symptoms of sickle cell disease usually begin in early childhood and may include anemia, repeated
infections, and periodic episodes of pain (called crises).

This condition is caused by mutations in the HBB gene and is inherited in an autosomal recessive pattern.

Treatment typically focuses on controlling symptoms and may include pain medicines during
crises; hydroxyurea to reduce the number of pain episodes; antibiotics and vaccines to prevent bacterial
infections; and blood transfusions.

On July 7, 2017, the FDA in the United States approved the use of Endari (prescription grade L-glutamine) to
reduce the number of sickle cell crisis.

Endari is the first FDA approved treatment that is also available for children with sickle cell disease five years
of age and older.
• Sickle cell anemia is inherited in an autosomal recessive pattern, which means that both copies
of the gene in each cell have mutations.

• The parents of an individual with an autosomal recessive condition each carry one copy of the
mutated gene, but they typically do not show signs and symptoms of the condition.

• In regards to sickle cell anemia, a person who carries one copy of the mutated gene is said to be
a carrier for the condition, or to have sickle cell trait.

• When two people who are carriers of an autosomal recessive condition have a child, there is a
25% (1 in 4) chance that the child will have the condition, a 50% (1 in 2) chance that the child will
be a carrier like each of the parents, and a 25% (1 in 4) chance that the child will not have the
condition and not be a carrier.
Mutations leading to sickle cell anemia
Hemoglobin is made up of four different protein subunits, which includes two subunits called alpha-globin and two called
beta-globin. Sickle cell anemia is caused by mutations in a gene called HBB, which is the gene that provides instructions for
the production of beta-globin.
There are multiple mutations that can occur in the HBB gene. One of these leads to the production of hemoglobin S.
Inheritance of sickle cell anemia:

Sickle cell anemia is an autosomal recessive disease, meaning that it only occurs if both the maternal and
paternal copies of the HBB gene are defective.
In other words, if an individual receives just one copy of the defective HBB gene, either from their mother or
their father, they do not have sickle cell anemia but have what is called “sickle cell trait”. People with sickle cell
trait usually do not have any symptoms or problems but they can pass the mutated gene onto their children.
There are three inheritance scenarios that can lead to a child having sickle cell anemia:

1.Both parents have sickle cell trait

If both parents have sickle cell trait, then there is a 25 percent risk of the child having sickle cell anemia and a 50
percent risk of them having sickle cell trait. There is also a 25 percent chance that the child will not inherit either
copy of the mutated gene.

2.One parent has sickle cell anemia and the other has sickle cell trait
If one parent has sickle cell anemia and the other has sickle cell trait, there is a 50 percent risk that their children
will have sickle cell anemia and 50 percent risk they will have sickle cell trait.

3.Both parents have sickle cell anemia

If both parents have sickle cell anemia, then their children will also definitely have the disease.
 PKU

• Phenylketonuria (commonly known as PKU) is an inherited disorder that

increases the levels of a substance called phenylalanine in the blood.
Phenylalanine is a building block of proteins (an amino acid) that is obtained
through the diet. It is found in all proteins and in some artificial sweeteners.
If PKU is not treated, phenylalanine can build up to harmful levels in the
body, causing intellectual disability and other serious health problems.
• The signs and symptoms of PKU vary from mild to severe. The most severe form of this disorder is known as
classic PKU.
• Infants with classic PKU appear normal until they are a few months old. Without treatment, these children
develop permanent intellectual disability.
• Seizures, delayed development, behavioral problems, and psychiatric disorders are also common.
• Untreated individuals may have a musty or mouse-like odor as a side effect of excess phenylalanine in the
body.
• Children with classic PKU tend to have lighter skin and hair than unaffected family members and are also
likely to have skin disorders such as eczema.
• Less severe forms of this condition, sometimes called variant PKU and non-PKU hyperphenylalaninemia, have
a smaller risk of brain damage. People with very mild cases may not require treatment with a low-
phenylalanine diet.
• This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell
have mutations.

• The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but
they typically do not show signs and symptoms of the condition.
 Eugenics

• Eugenics is the practice or advocacy of improving the human species by selectively

mating people with specific desirable hereditary traits. It aims to reduce human
suffering by “breeding out” disease, disabilities and so-called undesirable characteristics
from the human population.

• It deals with the application of the laws of genetics for the improvement of human race.
• The term Eugenics----Greek ‘Eugenes’= well born, was coined by an English scientist
Francis Galton in 1885.

• The science of eugenics can be defined as a science of well born, improving the inborn
qualities of race and obtaining the better heritage by judicious breeding.
• Early supporters of eugenics believed people inherited mental illness, criminal tendencies
and even poverty, and that these conditions could be bred out of the gene pool.
• Historically, eugenics encouraged people of so-called healthy, superior stock to reproduce
and discouraged reproduction of the mentally challenged or anyone who fell outside the
social norm.
• Modern eugenics, more often called human genetic engineering, has come a long way—
scientifically and ethically—and offers hope for treating many devastating genetic
illnesses.
• Eugenics is the science which deals with all influences that improve the inborn qualities
of a race; also with those that develop them to the utmost advantage.
• The improvement of the inborn qualities, or stock, of some one human population.
What is meant by improvement ?

What by the syllable E u in Eugenics, whose English equivalent is good?

• There is considerable difference between goodness in the several qualities and in that
of the character as a whole.

• The character depends largely on the proportion between qualities whose balance
may be much influenced by education.

• We must therefore leave morals as far as possible out of the discussion, not entangling
ourselves with the almost hopeless difficulties they raise as to whether a character as a
whole is good or bad.

• Moreover, the goodness or badness of character is not absolute, but relative to the
current form of civilization.
The aim of Eugenics is to bring as many influences as can be reasonably employed, to cause the useful
classes in the community to contribute more than their proportion to the next generation.
Set of beliefs and practices that aim to improve the genetic quality of the human population
● Attempt to only allow the “fit” to reproduce considered “positive” eugenics
● “Negative” eugenics prohibiting marriage and forced sterilization of those who are deemed “unfit”.
“Fit” was defined as:
○ High IQ
○ High socioeconomic class
○ Caucasian
• Positive eugenics existed for quite some time, even dating back to Plato who suggested selective mating
Negative eugenics came sometime after dating back to the late 19th century
Galton and Davenport felt like they were qualified to breed a better race because they
believed they were the best and the brightest.
- Sir Francis Galton, Considered to be the father of the eugenics movement
- After reading Darwin’s “On the Origin of Species” he changed his life goal from
mathematics and medicine to study the idea of evolution to improve the
human race
- Thought that a person’s environment had very little to do with the
development of these characteristics
- Social and mental traits, like talent and intelligence, were inherited
- Hereditary Genius - a compilation of his research on whether personality traits,
work ethic, and other traits were inherited
- It showed that success seemed to run in families
- He argues that this proved intelligence could be inherited
Charles Davenport Believed unfit came from backgrounds of low socioeconomic status
Favoured immigration restriction and sterilization
- Station for the Study of Experimental Evolution which later changed to
Department of Genetics at the Carnegie Institution of Washington
- Eugenic Record Office - is an archive of family histories that are used to study
and promote Eugenics
- This was then used to promote restrictions on immigration, segregation
of those deemed “unfit”, and the sexual sterilization legislation
- In 1935, the ERO was deemed unusable and unjustified and closed in
1939
- Vaguely defined and poorly collected, unreliable measures to gather
data, therefore he created stereotypes and inaccurate views so that
eugenics would gain popularity
- UNSCIENTIFIC