Professional Documents
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Submitted To:
Submitted By:-
Bharti Sharma
M.Sc. Biotechnology
Class:-10th
Roll No.5
Certificate
This is to certify that the project entitled, Genes And
Genetic Disorders" submitted by "Bharati Sharma" Roll
No. "5"in partial fulfillment of the requirements of for the
award of "9th Class" at the "St. Attri Public School" is an
authentic work carried out by her under my supervision and
guidance.
To the best of my knowledge, the matter embodied in the
project has not been submitted to any other School.
Date:
Mr. Paramjeet Sonkar
Acknowledgement
I wish to express my sincere gratitude to people who have
directly or indirectly contributed. On this report I have been
proportions to be blessed with Mr. Paramjeet Sonkar as my
mentor. I feel that he was the appropriate choice and I shall
remain obliged to him life long .I have learnt to be well
managed, punctual, Assidicous and at the same time , not to
give up to ticklish times. I have absolutely no words to
express my feelings for this lab.I wish to express my sincere
appreciation to Mr. Paramjeet Sonkar for his valuable
guidance, supervision and understanding throughout the
project work he made this study possible by helping and
encouragement me in all stage of my project work he made
this story possible by helping and encouragement me in all
stage of my project work. I wish to extent my thanks to for
helping me in the project. My special thanks are due to Mr.
Paramjeet Sonkar
Introduction
It is the differences that matter. You share about 75% of your genes
with your dog but it is the remaining doggy genes those which
make dogs have puppies not babies or kittens that we see as
important. Certainly it is the differences between people that interest
us when it comes to health and disease. Why do some live a long and
healthy life, whilst others develop life-threatening, chronic diseases in
mid-life or indeed are born with a disorder?
A popular response nowadays is to assume most of the difference lies
in our DNA in the 0.1% that we dont have in common with
everyone else. This is understandable given the excitement
surrounding the Human Genome Project and the ubiquitous use of the
DNA double helix icon in all things biomedical. But DNA alone is not
destiny.
Human development from conception to adulthood is an inseparable
partnership,
moulded within our cells, of Nature (the DNA we inherit) and Nurture
(the prevailing nutritional, social and physical environment). Our
DNA specifies the structure of proteins the primary chemical
building blocks of life but it is the cells circumstances that
ultimately determine when, where and how much of these proteins are
produced. The response may be a transient adjustment, but sometimes
our cells change for life, making different organs as the embryo
develops or when a childs life trajectory adjusts to the world in which
the child finds itself.
The study of these enduring changes, where life meets the genome, is
epigenetic.
Epigenetic discoveries will impact upon our understanding of child
development, mentalhealth, and how public health and well-being can
be maintained in a changing world.
Genetics and epigenetic go hand-in-hand, so this introductory booklet
covers both. Much of human genetic variation is a consequence,
through natural selection, of life challenging encounters during our
evolutionary history. Much can be learned when this evolved system
fails to cope and manifests as disease.
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DNA
DNA contains four chemicals (adenine, thymine, cytosine, and
guanine called A, T, C, and G for short) that are strung in patterns
on extremely thin, coiled strands in the cell. How thin? Cells are tiny
invisible to the naked eye and each cell in your body contains
about 6 feet of DNA thread, for a total of about 3 billion miles of
DNA inside you!
So where do genes come in? Genes are made of DNA, and different
patterns of A, T, G, and C code for the instructions for making things
your body needs to function (like the enzymes to digest food or the
pigment that gives your eyes their color). As your cells duplicate, they
pass this genetic information to the new cells.
DNA is wrapped together to form structures called chromosomes.
Most cells in the human body have 23 pairs of chromosomes, making
a total of 46. Individual sperm and egg cells, however, have just 23
unpaired chromosomes. You received half of your chromosomes from
your mother's egg and the other half from your father's sperm cell. A
male child receives an X chromosome from his mother and a Y
chromosome from his father; females get an X chromosome from
each parent.
Heredity
Heredity is the passing of genes from one generation to the next. You
inherit your parents' genes. Heredity helps to make you the person
you are today: short or tall, with black hair or blond, with brown eyes
or blue.
your genes can determine whether you'll be a straight-A student or a
great athlete Heredity plays an important role, but your environment
(including things like the foods you eat and the people you interact
with) also influences your abilities and interests.
A person can have changes (or mutations) in a gene that can cause
many issues for them. Sometimes changes cause little differences, like
hair color. Other changes in genes can cause health problems.
Mutation
Mutations in a gene usually end up causing that particular gene copy
to not do its job the way it normally should. Since we have two copies
of every gene, typically there's still a "normal" working copy of the
gene. In these cases, usually nothing out of the ordinary happens since
the body can still do the jobs it needs to do. This is an example of an
autosomalrecessive trait.
Researchers have identified more than 4,000 diseases that are caused
by mutations. But having a genetic mutation that may cause a disease
or condition doesn't always mean that a person will actually develop
that disease or condition.
On average, people probably carry from 5 to 10 genes with mutations
in each of their cells. Problems happen when the particular gene is
dominant or when a mutation is present in both copies of a recessive
gene pair. Problems can also happen when several variant genes
interact with each other or with the environment to increase
susceptibility to diseases.
Single-gene
A single-gene disorder is the result of a single mutated gene. Over
4000 human diseases are caused by single-gene defects. Single-gene
disorders can be passed on to subsequent generations in several ways.
Genomic imprinting and uniparental disomy, however, may affect
inheritance patterns. The divisions between recessive and dominant
types are not "hard and fast", although the divisions between
autosomal and X-linked types are (since the latter types are
distinguished purely based on the chromosomal location of the gene).
For example, achondroplasia is typically considered a dominant
disorder, but children with two genes for achondroplasia have a severe
skeletal disorder of which achondroplasics could be viewed as
carriers. Sickle-cell anemia is also considered a recessive condition,
but heterozygous carriers have increased resistance to malaria in early
childhood, which could be described as a related dominant condition.
When a couple where one partner or both are sufferers or carriers of a
single-gene disorder wish to have a child, they can do so through in
vitro fertilization, which means they can then have a preimplantation
genetic diagnosis to check whether the embryo has the genetic
disorder.
If a person has a change in a dominant gene that is associated with a
particular condition, he or she will usually have features of that
condition. And, each of the person's children will have a 1 in 2 (50%)
chance of inheriting the gene and developing the same features.
Diseases and conditions caused by a dominant gene include
achondroplasia (pronounced: ay-kon-druh-PLAY-zhuh, a form of
dwarfism),Marfan Syndrome (a connective tissue disorder), and
Huntington disease (a degenerative disease of the nervous system).
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People who have a change in just one copy of a recessive gene are
called "carriers." They don't usually have the disease because they
have a normal gene copy of that pair that can do the job. When two
carriers have a child together, however, the child has a 1 in 4 (25%)
chance of getting a gene with a mutation from both parents, which
would result in the child having the disease. Cystic Fibrosis (a lung
disease), Sickle Cell Anemia(a blood disorder), and Tay-Sachs disease
(which causes nervous system problems) are caused by recessive
mutations from both parents coming together in a child.
With recessive gene mutations on the X chromosome, usually only
guys can develop the disease because they have only one X
chromosome. Girls have two X chromosomes since they have a
back-up copy of another X chromosome, they don't always show
features of X-linked conditions. These include the bleeding disorder
hemophilia(pronounced: hee-muh-FIL-ee-uh) and color blindness.
Sometimes when an egg and sperm unite, the new cell gets too many
or too few chromosomes, which can cause issues for the child. For
example, most children born with Down syndrome have an extra
chromosome number 21.
Autosomal recessive
Two copies of the gene must be mutated for a person to be affected by
an autosomal recessive disorder. An affected person usually has
unaffected parents who each carry a single copy of the mutated gene
(and are referred to as carriers). Two unaffected people who each
carry one copy of the mutated gene have a 25% risk with each
pregnancy of having a child affected by the disorder. Examples of this
type of disorder are Albinism, Medium-chain acyl-CoA
dehydrogenase deficiency, cystic fibrosis, sickle-cell disease, TaySachs disease, Niemann-Pick disease, spinal muscular atrophy, and
Roberts syndrome. Certain other phenotypes, such as wet versus dry
earwax, are also determined in an autosomal recessive fashion.
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X-linked dominant
X-linked dominant disorders are caused by mutations in genes on the
X chromosome. Only a few disorders have this inheritance pattern,
with a prime example being X-linked hypophosphatemic rickets.
Males and females are both affected in these disorders, with males
typically being more severely affected than females. Some X-linked
dominant conditions, such as Rett syndrome, incontinentia pigmenti
type 2, and Aicardi syndrome, are usually fatal in males either in
utero or shortly after birth, and are therefore predominantly seen in
females. Exceptions to this finding are extremely rare cases in which
boys with Klinefelter syndrome (47,XXY) also inherit an X-linked
dominant condition and exhibit symptoms more similar to those of a
female in terms of disease severity. The chance of passing on an Xlinked dominant disorder differs between men and women. The sons
of a man with an X-linked dominant disorder will all be unaffected
(since they receive their father's Y chromosome), and his daughters
will all inherit the condition. A woman with an X-linked dominant
disorder has a 50% chance of having an affected fetus with each
pregnancy, although it should be noted that in cases such as
incontinentia pigmenti, only female offspring are generally viable. In
addition, although these conditions do not alter fertility per se,
individuals with Rett syndrome or Aicardi syndrome rarely reproduce.
X-linked recessive
X-linked recessive conditions are also caused by mutations in genes
on the X chromosome. Males are more frequently affected than
females, and the chance of passing on the disorder differs between
men and women. The sons of a man with an X-linked recessive
disorder will not be affected, and his daughters will carry one copy of
the mutated gene. A woman who is a carrier of an X-linked recessive
disorder (XRXr) has a 50% chance of having sons who are affected
and a 50% chance of having daughters who carry one copy of the
mutated gene and are therefore carriers. X-linked recessive conditions
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Y-linked
Y-linked disorders, also called holandric disorders, are caused by
mutations on the Y chromosome. These conditions display may only
be transmitted from the heterogametic sex (e.g. male humans) to
offspring of the same sex. More simply, this means that Y-linked
disorders in humans can only be passed from men to their sons;
females can never be affected because they do not possess Y
allosomes.
Y-linked disorders are exceedingly rare but the most well-known
examples typically cause infertility. Reproduction in such conditions
is only possible through the circumvention of infertility by medical
intervention.
Mitochondrial
This type of inheritance, also known as maternal inheritance, applies
to genes in mitochondrial DNA. Because only egg cells contribute
mitochondria to the developing embryo, only mothers can pass on
mitochondrial conditions to their children. An example of this type of
disorder is Leber's hereditary optic neuropathy.
Some of the Single Gene Disorders are as follows
Cystic fibrosis is a genetic disorder that affects the respiratory and
digestive systems.
People with cystic fibrosis inherit a defective gene on chromosome 7
called CFTR (cystic fibrosis transmembrane conductance regulator).
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2.Galactosemia
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The body breaks down lactose into galactose and glucose and uses
these sugars for energy. Most people with galactosemia are missing an
enzyme (called GALT) that helps further break down galactose.
Defects in galactose metabolism cause toxic chemicals to build up in
cells of the body.
Diagnosis And Treatment
Defects in galactose metabolism can cause several severe symptoms,
including kidney failure, an enlarged liver, cataracts (clouding of the
eye lens), poor growth, and intellectual disability.
People can inherit a milder form of the disorder when a different
gene, also involved in galactose metabolism, is mutated. These
patients often suffer from cataracts, but not the other symptoms
associated with classical galactosemia.
In most states, babies are tested for galactosemia at birth. Using a tiny
blood sample taken from the baby's heel, the test checks for low levels
of the GALT enzyme. This allows for prompt treatment, which can
substantially prevent the serious symptoms of this disorder.
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Multiple-Gene
Genetic disorders may also be complex, multifactorial, or polygenic,
meaning they are likely associated with the effects of multiple genes
in combination with lifestyles and environmental factors.
Multifactorial disorders include heart disease and diabetes. Although
complex disorders often cluster in families, they do not have a clearcut pattern of inheritance. This makes it difficult to determine a
persons risk of inheriting or passing on these disorders. Complex
disorders are also difficult to study and treat, because the specific
factors that cause most of these disorders have not yet been identified.
Studies which aim to identify the cause of complex disorders can use
several methodological approaches to determine genotype-phenotype
associations. One method, the genotype-first approach, starts by
identifying genetic variants within patients and then determining the
associated clinical manifestations. This is opposed to the more
traditional phenotype-first approach, and may identify causal factors
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Alzheimer's Disease
The most common form of the disease, which strikes after age 65, is
linked to the apolipoprotein E (apoE) gene on chromosome 19.
Scientists don't know how apoE4 increases the risk of developing
Alzheimer's. They do know that everyone has apoE, which comes in
three forms.
One of the forms (apoE4) increases a person's risk of developing
Alzheimer's. The other two forms seem to protect against the disease.
While people who inherit the apoE4 form of the gene are at increased
risk for the disease, they will not necessarily develop it.
Mutations in genes found on chromosomes 1, 14, and 21 are linked to
rarer forms of the disease, which strike earlier in life.
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Diagnosis
Due to the wide range of genetic disorders that are presently known,
diagnosis of a genetic disorder is widely varied and dependent of the
disorder. Most genetic disorders are diagnosed at birth or during early
childhood, however some, such as Huntington's disease, can escape
detection until the patient is well into adulthood.
The basic aspects of a genetic disorder rests on the inheritance of
genetic material. With an in depth family history, it is possible to
anticipate possible disorders in children which direct medical
professionals to specific tests depending on the disorder and allow
parents the chance to prepare for potential lifestyle changes, anticipate
the possibility of stillbirth, or contemplate termination. Prenatal
diagnosis can detect the presence of characteristic abnormalities in
fetal development through ultrasound, or detect the presence of
characteristic substances via invasive procedures which involve
inserting probes or needles into the uterus such as in amniocentesis.
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Hypothyroidism
The thyroid is the largest endocrine gland in the body. It sits just
below the larynx (voice box) and wraps around the trachea
(windpipe). The thyroid gland produces thyroid hormone, which helps
the body grow and develop. It also plays an important role in the
body's metabolism (the processes in the body that use energy, such as
eating, breathing, and regulating heat).
Hypothyroidism (or underactive thyroid) is a common condition in
which the thyroid gland makes too little thyroid hormone. About 1 in
5,000 babies is born with congenital hypothyroidism, in which the
thyroid fails to grow normally and cannot produce enough hormone.
There is no known cause for most cases of congenital
hypothyroidism. But about 10 to 20 percent of the time, the condition
is caused by an inherited defect that alters the production of thyroid
hormone.
The most common inherited form of hypothyroidism is a defect of the
TPO (thyroid peroxidase) gene on chromosome 2. This gene plays an
important role in thyroid hormone production.
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Symptoms of hypothyroidism
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When the body has too little thyroid hormone, the pituitary gland
works overtime, making extra thyroid-stimulating hormone (TSH).
Having too much TSH may enlarge the thyroid, forming a goiter.
Diagnose
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Still, for many people who have genetic diseases, gene therapy holds
the hope that they or their children will be able to live better,
healthier lives.
Conclusion
The last 20 years have seen great technical advances in the analysis of
DNA and the completion of the Human Genome Project in 2003.
These advances led to the discovery of which faulty genes cause
which of the many simply-inherited (Mendelian) geneti diseases. This
knowledge has given rise to greater understanding of the molecular
basis of many Mendelian diseases, and why they have the inheritance
pattern they do. Some diseases are caused by a single faulty gene, but
do not follow a Mendelian pattern of inheritance. Research into one of
these diseases, Fragile X syndrome, revealed that a DNA fault can
enlarge over three generations (a dynamic mutation) until a nearby
gene is silenced (switched off). Another disease, Angelman syndrome,
confirmed that some human genes are normally subject to genomic
imprinting, a phenomenon in which a gene is silenced depending on
whether it was inherited from father or from mother. The molecular
silencing process (DNA methylation) involved in genomic imprinting
is a
classic example of epigenetic regulation, in which there is an enduring
change in gene activity but without any change in DNA sequence.
Epigenetic regulation underpins normal development from the
fertilised egg to an embryo with its many different cell types and
organs, and may also be involved in response to early life
experiences. Understanding the role of numerous genetic variations
and epigenetic regulation in common, multifactorial disorders such
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