: GENE STRUCTURE

LECTURE 1

AND CHROMOSOMES
LENNOX MAC-ANKRAH
 OUTLINE
■ INTRODUCTION TO GENETICS

■ HISTORY OF GENETICS

■ CHROMOSOME STRUCTURE

■ TELOMERE AND ITS FUNCTION

■ LOCATING A GENE ON A CHROMOSOME

■ KARYOTYPING

■ LEVELS OF GENETIC ANALYSIS

 INTRODUCTION
■ Genetics is the study of heredity and the variation of inherited
characteristics.

■ Heredity is a biological process where a parent passes certain genes onto

their children or offspring.

■ Variation refers to a genetic change that causes differing characteristics

between organisms in a certain species

■ Every child inherits genes from both of their biological parents and these
genes in turn express specific traits.
■ Some of these traits may be physical for example hair and eye color and
skin color etc.

■ On the other hand some genes may also carry the risk of certain diseases
and disorders that may pass on from parents to their offspring.

■ A gene is a locus (or region) of DNA which is made up of nucleotides and is

the molecular unit of heredity

■ The history of genetics started with the work of the Gregor Johann Mendel.
■ His work on pea plants, published in 1866, described what came to
be known as Mendelian inheritance. Many theories of heredity
proliferated in the centuries before and for several decades after
Mendel's work

■ The human genome contains 46 chromosomes. Human sperm and

eggs, which have only one homologous chromosome from each pair,
are said to be haploid (1n).

■ The genome contains approximately 3 billion base pairs and about

20,000 genes (that encode proteins)
■ DNA sequence in any two people is 99.9% identical – only 0.1% is
unique!

■ Only about 1.2% of our genome encode proteins and the other 98.8%
is non coding DNA .

■ Some of the non coding DNA code for RNA molecules and regulatory
elements
A summary of the structural relationship between genes, DNA and
chromosomes
Nucleus
(control centre of the cell, containing chromosomes)

Chromosomes
(long strands of DNA, tightly coiled around histone proteins)

DNA
(heredity material, carrying all the genetic information)

Gene
(short section of DNA determining a specific characteristic of a cell/organism)
 HISTORY OF GENETICS
■ 1859 Charles Darwin Natural Selection
■ 1865 Gregor Mendel Heredity Transmitted in Units
■ 1869 Frederick Miescher DNA Isolated
■ 1879 Walter Flemming Mitosis Described
■ 1900 DeVries, Correns, and von Tschermak Rediscovery of
Mendel’s work
■ 1902 Walter Sutton Chromosome Theory of Inheritance
■ 1902 Archibald Garrod Orderly Inheritance of
Disease_alkaptonuria
■ 1909 Wilhelm Johannsen The Word Gene is Coined. He also
uses the terms genotype and phenotype
■ 1911 Thomas Hunt Morgan : Chromosomes Carry Genes
■ 1941 George Beadle and Edward Tatum One Gene, One Enzyme
Hypothesis
■ 1943 William Astbury DNA Has a Regular Periodic Structure
■ 1944 Oswald Avery, Colin MacLeod, and Maclyn McCarty DNA
Transforms Cells
■ 1944 Barbara McClintock Jumping Genes
■ 1952 Alfred Hershey & Martha Chase Genes Are Made of DNA
■ 1953 Francis H. Crick and James D. Watson DNA Double Helix
■ 1955 Joe Hin Tjio 46 Human Chromosomes
■ 1955 Arthur Kornberg and colleagues isolated DNA polymerase
■ 1956 Vernon Ingram Cause of Disease Traced to Alteration
■ 1958 Matthew Meselson and Franklin Stahl Semiconservative
Replication of DNA
■ 1959 Jerome Lejeune and his colleagues : Chromosome
Abnormalities Identified
■ 1961 Robert Guthrie First Screen for Metabolic Defect in
Newborns
■ 1961 Sydney Brenner, François Jacob and Matthew Meselson
mRNA Ferries Information
■ 1966 Marshall Nirenberg and others Genetic Code Cracked
■ 1975 , Frederick Sanger and colleagues, and Alan Maxam and
Walter Gilbert, DNA Sequencing
■ 1977 Richard Roberts’ and Phil Sharp : Introns Discovered
■ 1983 : PCR Invented
■ 1990 Launch of the Human Genome Project
■ 2003 Completion of the Human Genome Sequencing

NB
■ The term genetics was named by William Bateson
■ Edmund B. Wilson discovered the X chromosome in a butterfly
■ Nettie Stevens discovered the Y chromosome in beetle.
 CHROMOSOMES
■ In a cell, DNA does not usually exist by itself, but instead
associates with specialized proteins that organize it and give it
structure.

■ In eukaryotes, these proteins include the histones, a group of

basic (positively charged) proteins that form “bobbins” around
which negatively charged DNA can wrap.
■ In addition to organizing DNA and making it more compact,
histones play an important role in determining which genes are
active.

■ The complex of DNA plus histones and other structural proteins is

called chromatin
Histone And Chromosome Structure
■ For most of the life of the cell, chromatin is decondensed,
meaning that it exists in long, thin strings under the microscope.

■ In this state, the DNA can be accessed relatively easily by cellular

machinery (such as proteins that read and copy DNA), which is
important in allowing the cell to grow and function

■ Condensation takes place when the cell is about to divide.

■ Bacteria also have chromosomes, but their chromosomes are

typically circular
■ Chromosomes are not visible in the cell’s nucleus—not even under a
microscope—when the cell is not dividing. However, the DNA that
makes up chromosomes becomes more tightly packed during cell
division and is then visible under a microscope.

■ Most of what researchers know about chromosomes was learned by

observing chromosomes during cell division.

■ Each chromosome has a constriction point called the centromere,

which divides the chromosome into two sections, or “arms.” The short
arm of the chromosome is labeled the “p arm.” The long arm of the
chromosome is labeled the “q arm.”
■ The location of the centromere on each chromosome gives the
chromosome its characteristic shape, and can be used to help
describe the location of specific genes.

■ The symbol "p" was chosen to designate the short arm because "p"
stands for "petit", "small" in French. The letter "q" was selected to
signify the long arm merely because "q" is the next letter in the
alphabet.
 Development and chromosomes
■ Differences in chromosomes are associated with difference in the
way we grow.

■ The karyograms of males and females are not the same

Females have two large X chromosomes
Males have a large X and a small Y chromosome
The X and the Y chromosomes are called sex chromosomes
The sex chromosomes are placed at the end of the karyotype

■ Unusual growth can be associated with chromosome abnormalities

e.g. People who develop Down syndrome have trisomy 21
 DEFINITION OF CHROMOSOME

▪ It is a combination of two words, i.e., “Chroma”-means ‘colour’

and “Somes”-means ‘body’.

▪ So the coloured thread like bodies present in the nucleoplasm o

f the living cells, which helps in the inheritance (transmission) of
characters in form of Genes from generation to generation are k
nown as CHROMOSOMES.
 NUMBER OF CHROMOSOMES
The number of chromosomes per organism is always a definite
number, Which is said as Diploid (2n) no., but gametes, sperms, ova
etc. carry Haploid (n) number. Some examples are given below.
PHYSICAL STRUCTURE
❖Size varies from 1 to 30 micron in length and diameter from 0.2
to 2 micron.
❖CENTROMERE:- The non-stainable part of the chromosome
making a primary constriction.
❖CHROMATIDS:- Two chromatids join at the centromere to form
a chromosome.
❖CHROMONEMA:- In each chromatid, there are two longitudinal
chromonemata coiled with each other.
❖CHROMOMERES:- In each chromonemata, there are “bead”
like chromomeres present through out the coil.
❖GENES:- Each chromomeres contains genes, the unit of
inheritance of character.
 TYPES OF CHROMOSOMES
Based on centromere position

1. TELOCENTRIC:- The centromere is CENTROMERE

present at the end of the chromosomes.

None in humans but found in mice.

LONG ARM
SHORT ARM

CENTROMERE
2. ACROCENTRIC:-The centromere i
s almost terminal. It has one large and
LONG ARM another very small arm. Human
chromosomes 13, 14, 15, 21 and 22
 TYPES OF CHROMOSOMES
(CONTINUED)

SHORT ARM 3. SUB-METACENTRIC:- Here the centromere

is not at the middle position of the
CENTROMERE
chromosomes. So the arms are unequal and it
is ‘L-Shaped’ in appearance.
Human chromosomes 4 to 12

LONG ARM
TWO EQUAL ARMS

4. METECENTRIC:- The centromere

is at the middle position. So the arms
are equal and it is ‘V-Shaped’ in app
CENTROMERE
earance.
Human chromosomes 1 and 3
 TELOMERE
■ Telomeres are an essential part of human cells that affect how our cells
age. Made up of DNA sequemces and proteim.

■ A telomere is a region of repetitive nucleotide sequences at each end

of a chromosome, which protects the end of the chromosome from
deterioration or from fusion with neighboring chromosomes

■ Telomeres are the caps at the end of each strand of DNA that protect
our chromosomes, like the plastic tips at the end of shoelaces
■ Our cells replenish by copying themselves. This happens constantly
throughout our lives.

■ Telomeres get shorter each time a cell copies itself, but the important
DNA stays intact.

■ Eventually, telomeres get too short to do their job, causing our cells to
age and stop functioning properly. Therefore, telomeres act as the
aging clock in every cell.
■ We inherit telomeres from our parents, but no matter the length of our
telomeres at birth, everyone’s get shorter as they age.

■ Shorter telomeres have a negative effect on our health.

Telomere shortening is the main cause of age-related break down of
our cells.

■ When telomeres get too short, our cells can no longer reproduce,
which causes our tissues to degenerate and eventually die.
■ Some cells, like those found in the skin, hair and immune system, are
most affected by telomere shortening because they reproduce more
often.

■ In humans the telomere sequence is TTAGGG.

■ This sequence is usually repeated about 3,000 times and can reach up
to 15,000 base pairs in length.
Telomeres serve three major purposes:

■ They help to organise each of our 46 chromosomes in the nucleus of

our cells

■ They protect the ends of our chromosomes by forming a cap. If the

telomeres were not there, our chromosomes may end up sticking to
other chromosomes.

■ They allow the chromosome to be replicated properly during cell

division:
– Every time a cell carries out DNA replication the chromosomes are
shortened by about 25-200 bases (A, C, G, or T) per replication.

– However, because the ends are protected by telomeres, the only part
of the chromosome that is lost, is the telomere, and the DNA is left
undamaged.

– Without telomeres, important DNA would be lost every time a cell

divides (usually about 50 to 70 times). This would eventually lead to
the loss of entire genes
 HOW IS TELOMERE LENGTH MAINTAINED
■ Telomerase is an enzyme that adds the TTAGGG telomere sequence to
the ends of chromosomes.

■ Telomerase is only found in very low concentrations in our somatic

cells. Because these cells do not regularly use telomerase they age
leading to a reduction in normal function. The result of ageing cells, is
an ageing body.

■ Telomerase is found in high levels in germline cells (egg and sperm)

and stem cells. In these cells telomere length is maintained after DNA
replication and the cells do not show signs of ageing.
■ Telomerase is also found in high levels in cancer? cells. This enables
cancer cells to be immortal and continue replicating themselves.

■ If telomerase activity was switched off in cancer cells, their telomeres

would shorten until they reached a ‘critical length’. This would, prevent
the cancer cells from dividing uncontrollably to form tumours.

■ The action of telomerase allows cells to keep multiplying and avoid

ageing
 TELOMERE AND LIFESTYLE CHOICES
– Lifestyle factors such as smoking, lack of physical activity, obesity,
stress, exposure to pollution etc can potentially increase the rate of
telomere shortening, cancer risks, and pace of aging.

– Dietary restriction , appropriate diet rich in high fiber, antioxidants ,

lean or low protein, soy protein to diet and regular exercise can
potentially reduce the rate of telomere shortening , disease risk , and
pace of aging.
 Locating a gene on a chromosome
■ Geneticists use maps to describe the location of a particular gene on
a chromosome.

■ One type of map uses the cytogenetic location to describe a gene’s

position.

■ The cytogenetic location is based on a distinctive pattern of bands

created when chromosomes are stained with certain chemicals.

■ Another type of map uses the molecular location, a precise

description of a gene's position on a chromosome. The molecular
location is based on the sequence of DNA building blocks (base pairs)
that make up the chromosome
 Cytogenetic location
■ Geneticists use a standardized way of describing a gene's cytogenetic
location. In most cases, the location describes the position of a
particular band on a stained chromosome: 17q12

■ It can also be written as a range of bands, if less is known about the

exact location: 17q12-q21

■ The combination of numbers and letters provide a gene's “address” on

a chromosome.
■ This address is made up of several parts:
1. The chromosome on which the gene can be found. The first number
or letter used to describe a gene's location represents the
chromosome. Chromosomes 1 through 22 (the autosomes) are
designated by their chromosome number. The sex chromosomes
are designated by X or Y.

2. The arm of the chromosome.. For example, 5q is the long arm of

chromosome 5, and Xp is the short arm of the X chromosome.
3. The
position of the gene on the p or q arm. The position of a gene is
based on a distinctive pattern of light and dark bands that appear
when the chromosome is stained in a certain way.

▪ The position is usually designated by two digits (representing a

region and a band), which are sometimes followed by a decimal
point and one or more additional digits (representing sub-bands
within a light or dark area).
■ The number indicating the gene position increases with
distance from the centromere. For example: 14q21
represents position 21 on the long arm of chromosome 14.
14q21 is closer to the centromere than 14q22.
 Additional information
■ Sometimes, the abbreviations “cen” or “ter” are also used to describe
a gene's cytogenetic location. “Cen” indicates that the gene is very
close to the centromere. For example, 16pcen refers to the short arm
of chromosome 16 near the centromere. “

■ Ter” stands for terminus, which indicates that the gene is very close to
the end of the p or q arm. For example, 14qter refers to the tip of the
long arm of chromosome 14.
■ “Tel” is also sometimes used to describe a gene's location. “Tel”
stands for telomeres, which are at the ends of each chromosome.
The abbreviations “tel” and “ter” refer to the same location
The CFTR gene is located on the long arm of
chromosome 7 at position 7q31.2
 Molecular location
■ The Human Genome Project, an international research effort
completed in 2003, determined the sequence of base pairs for each
human chromosome.

■ This sequence information allows researchers to provide a more

specific address than the cytogenetic location for many genes.

■ A gene’s molecular address pinpoints the location of that gene in terms

of base pairs.
■ It describes the gene’s precise position on a chromosome and
indicates the size of the gene.

■ Knowing the molecular location also allows researchers to determine

exactly how far a gene is from other genes on the same chromosome.
 KARYOTYPING
■ A karyotype is simply a picture of a person’s chromosomes.

■ In order to get this picture, the chromosomes are isolated, stained, and
examined under the microscope.

■ Most often, this is done using the chromosomes in the white blood
cells. A picture of the chromosomes is taken through the microscope.

■ Then, the picture of the chromosomes is cut up and rearranged by the

chromosome’s size. The chromosomes are lined up from largest to
smallest. A trained cytogeneticist can look for missing or extra pieces
of chromosome
■ There are 22 numbered pairs of chromosomes called autosomes.

■ The 23rd pair of chromosomes are the sex chromosomes. They

determine an individual’s gender.

■ Females have two X chromosomes, Each chromosome has been

assigned a number based on its size.
 KARYOTYPING
■ Karyotyping is a laboratory procedure that allows a doctor to examine
ones set of chromosomes. .

■ Examining chromosomes through karyotyping allows a doctor to

determine whether there are any abnormalities or structural problems
within the chromosomes

■ When a cell isn’t in the process of division, the chromosomes are

arranged in a spread out, unorganized way. During division, the
chromosomes in these new cells line up in pairs.
■ A karyotype test examines these dividing cells. The pairs of
chromosomes are arranged by their size and appearance. This helps
doctors easily determine if any chromosomes are missing or damaged.
 WHY IS IT USEFUL?
■ An unusual number of chromosomes, incorrectly arranged
chromosomes, or malformed chromosomes can all be signs of a
genetic condition.

■ The test is also useful for identifying the Philadelphia chromosome.

Having this chromosome can signal chronic myelogenous leukemia
(CML)., Down syndrome and Turner syndrome.

■ Babies can be karyotype tested before they’re born to diagnose

genetic abnormalities that indicate serious birth defects, such as
Klinefelter syndrome. In Klinefelter syndrome, a boy is born with an
extra X chromosome
 HOW IS IT DONE ?
■ The first step in karyotyping is to take a sample of your cells. The
sample cells can come from a number of different tissues. This can
include:

➢ bone marrow
➢ blood
➢ amniotic fluid
➢ placenta

■ Sampling can be done using various methods, depending on which

area of your body is being tested. For example, the doctor will use
amniocentesis to collect the sample if amniotic fluid needs to be
■ After the sample has been taken, it’s placed in a laboratory dish that
allows the cells to grow. A lab technician will take cells from the
sample and stain them. This makes it possible for your doctor to view
the chromosomes under a microscope.

▪ These stained cells are examined under a microscope for potential

abnormalities. Abnormalities can include:

➢ extra chromosomes
➢ missing chromosomes
➢ missing portions of a chromosome

➢ extra portions of a chromosome

➢ portions that have broken off of one chromosome and reattached to

another

■ The lab technician can see the chromosomes’ shape, size, and
number. This information is important in determining if there are any
abnormalities.
■ Test results may be skewed if one is undergoing chemotherapy.
Chemotherapy can cause breaks in chromosomes, which will appear
in the resulting images genetic abnormalities

■ Complications can sometimes result from these testing methods, but

they’re rare. There’s a slight risk of bleeding and infection from having
blood drawn or having your bone marrow biopsied. Amniocentesis
carries a very minimal risk of miscarriage
 Levels of Genetic Analysis
■ Genetic analysis is practiced at different levels. The oldest type of
genetic analysis follows in Mendel’s footsteps

■ Another type of genetic analysis follows in the footsteps of Watson and

Crick and the army of people who have worked on the various genome
projects

■ Still another type of genetic analysis imitates Darwin and Wallace by

focusing on entire populations of organisms

■ All these levels of genetic analysis are routinely used in research

today
 Levels of Genetic Analysis
■ In classical genetic analysis, genes are studied by following the
inheritance of traits in crosses between different strains of an
organism.

■ In molecular genetic analysis, genes are studied by isolating,

sequencing, and manipulating DNA and by examining the products of
gene expression.

■ In population genetic analysis, genes are studied by assessing the

variability among individuals in a group of organisms
 READING ASSIGNMENTS

■ Read on model organisms used in the study of

genetics
■ Read on scientists who contributed to the
development of the field of genetics
END OF LECTURE 1