2. • Human genetics is the study of the inheritance of characteristics by children
from parents.
• Human genetics encompasses a variety of overlapping fields including: classical
genetics, cytogenetics, molecular genetics, biochemical genetics, genomics,
population genetics, developmental genetics, clinical genetics, and genetic
counselling.
3. INHERITANCE OF TRAITS IN HUMANS
• An inherited trait is one that is genetically determined.
• Inherited traits are passed from parent to offspring.
• EX. In humans- eye color, hair color, skin color, freckles, dimples, etc. are all
examples of inherited traits
• EX. In animals- eye color, fur color and texture, facial shape, etc. are examples
of inherited traits.
4. PEDIGREE ANALYSIS
• A very important tool for studying human inherited diseases
• These diagrams make it easier to visualize relationships with in families, particularly
large extended families.
• Pedigrees are often used to determine the mode of inheritance (dominant, recessive,
etc.) of genetic diseases.
• Pedigrees are diagrams that show the relationship among the members of the family.
8. CATEGORIES OF INHERITANCE
• Humans have 23 pairs of chromosomes--22 pairs of numbered chromosomes, called
autosomes, and one pair of sex chromosomes, X and Y.
1.Autosomal Recessive:
• To have an autosomal recessive disorder, you inherit two mutated genes, one from
each parent.(mm-both genes must be mutated for the progeny)
• These disorders are usually passed on by two carriers.
• Their health is rarely affected, but they have one mutated gene (recessive gene) and one
normal gene (dominant gene) for the condition(For Carriers).
• Examples: Cystic fibrosis, sickle cell anemia, and Tay-Sachs disease.
10. 2. Autosomal Dominant:
• "Dominant" means that a single
copy of the disease-associated
mutation is enough to cause the
disease. (m+)
• Some autosomal dominant traits
are neurofibromatosis Type I,
Huntington disease, and
Marfan syndrome.
11. 3. X-linked recessive:
• X-linked recessive inheritance refers to genetic conditions associated with
mutations in genes on the X chromosome.
• A male carrying such a mutation will be affected, because he carries only one
X chromosome.
• A female carrying a mutation in one gene, with a normal gene on the other X
chromosome, is generally unaffected.(XX-rr affected, XX-Rr unaffected,XY-
rR affected)
Example :Color-blindness, hemophilia
12.
13. 4. X linked dominant:
• X-linked dominant inheritance refers to genetic conditions associated with
mutations in genes on the X chromosome.
• A single copy of the mutation is enough to cause the disease in both males
(who have one X chromosome) and females (who have two X
chromosomes).
• Ex, Hypophosphatemia.
5.Y-linked (meaning the allele is found on the Y chromosome and can only be
in males.
14.
15. NAIL PATELLA SYNDROME
• Nail patella syndrome (NPS) is an autosomal dominant condition affecting the
nails, skeletal system, kidneys and eyes.
• Nail patella syndrome (NPS) also known as hereditary osteoonychodysplasia
(HOOD), Fong disease, Turner-Kieser syndrome, and Österreicher-Turner
syndrome, is a pleiotropic condition with a classical clinical tetrad involving the
nails, knees, elbows.
• It mainly results in small, poorly developed nails, knee caps, elbows ,chest and
hips. The name ‘nail patella’ is very misleading because this affects many other
areas of body not only nails including the production of certain proteins.
16.
17. Symptoms
• Knees are unstable and patella are smaller.
• Limited motion of elbows.
• Radial head subluxation
• Erythrodysplasia of elbow.
• Exostoses from iliac bones.
• Scoliosis.
• Scapular hypoplasia.
• Loss of peripheral vision.
• Blind spots.
• Blurred vision.
• Severe headache.
• Nausea.
• Eye pain in rare cases.
• Osteoporosis
18. • Nail-patella syndrome is inherited in an autosomal dominant pattern, which means one
copy of the altered gene in each cell is sufficient to cause the disorder.
• An affected person inherits the mutation from one affected parent.
• Other cases may result from new mutations in the LMX1B gene. These cases occur in
people with no history of the disorder in their family.
• When a person who has a genetic change in the LMX1B gene has children, for each
child there is a:
50% chance to inherit the changed copy of the LMX1B gene, meaning he or she will have nail-
patella syndrome
50% chance to inherit the working copy of the LMX1B gene, meaning he or she will not have nail-
patella syndrome
19. • About 88% of people with nail-patella syndrome have a genetic change in the
LMX1B gene that is inherited from a parent.
• In about 12% of people with nail-patella syndrome, the genetic change in the
LMX1B gene was not inherited from either parent.
• The genetic change was new in the person diagnosed with nail-patella
syndrome.
20.
21. Q. Study the pedigree and answer the question for nail patella syndrome.
22. • Nail-patella syndrome is an autosomal disorder affecting the shape of nails on
fingers and toes, as well as the structure of kneecaps. The pedigree shows the
transmission of nail-patella syndrome in a family along with ABO blood type.
• Is nail-patella syndrome a dominant or a recessive condition?
• Does this family give evidence of genetic linkage between nail-patella
syndrome and ABO blood group?
23. • By looking at the pedigree, we can see that in almost all cases, individuals
with nail-patella syndrome also posses the A allele.
• This strongly suggests that the nail-patella and blood type genes are
linked, and that the dominant allele responsible for the disease is in
coupling with the A allele at the blood type locus as given in the example
above.(Detecting and Measuring Linkage in Humans)
25. ADA DEFICIENCY
• Adenosine deaminase (also known as adenosine aminhydrolase or ADA) is
an enzyme involved in purine metabolism.
• It is needed for the breakdown of adenosine from food and for the turnover
of nucleic acids in tissues.
• In all mammalian cells, its primary function in humans is the development
and maintenance of the immune system.
26. • Adenosine deaminase deficiency (ADA deficiency) is an inherited condition that damages the
immune system.
• Common cause of severe combined immunodeficiency (SCID).
• People with SCID due to ADA deficiency are unable to fight off most types of infections,
including bacterial, viral and fungal infections.
INHERITANCE
• The enzyme adenosine deaminase is encoded by a gene on chromosome 20;q12-q13 .
• ADA deficiency is inherited in an autosomal recessive manner. This means the defective
gene responsible for the disorder is located on an autosome (chromosome 20 is an autosome).
• Two copies of the defective gene (one inherited from each parent) are required in order to be
born with the disorder.
27. • The parents of an individual with an autosomal recessive disorder both carry one copy of
the defective gene, but usually do not experience any signs or symptoms of the disorder.
28. IMMUNE DEFECTS
• Adenosine deaminase deficiency SCID, commonly called ADA SCID.
• It is caused by a mutation in the gene that encodes a protein called adenosine deaminase
(ADA).
• This ADA protein is an essential enzyme needed by all body cells to produce new DNA.
• This enzyme also breaks down toxic metabolites that otherwise accumulate to harmful levels
that kill lymphocytes.
• People afflicted with this disease often have to take antibiotics and supplemental infusions of
antibodies to protect themselves from serious infections.
• They can also receive adenosine deaminase injections given once or twice a week. ADA
SCID is lethal without treatment.
29. What Is Severe Combined Immunodeficiency
• It is a type of primary immune deficiency.
• SCID is a "combined" immunodeficiency because it affects both of T cells
and B cells infection-fighting white blood cells.
• In SCID, the child's body has too few lymphocytes or lymphocytes that don't
work properly.
• Because the immune system doesn't work as it should, it can be difficult or
impossible for it to battle the germs — viruses , bacteria , and fungi — that
cause infections.
30. • It is also known as the bubble boy disease and bubble baby
disease because its victims are extremely vulnerable to
infectious diseases and some of them, such as David Vetter,
have become famous for living in a sterile environment.
• The most common treatment for SCID is bone marrow
transplantation.
• A treatment for patients with ADA-SCID is enzyme
replacement therapy, in which the patient is injected with
polyethyleneglycol-coupled adenosine deaminase (PEG-
ADA) which metabolizes the toxic substrates of the ADA
enzyme and prevents their accumulation.
32. • Is an inherited form of anemia — a
condition in which there aren't enough
healthy red blood cells to carry adequate
oxygen throughout your body.
• In sickle cell anemia, the red blood cells
become rigid and sticky and are shaped like
sickles or crescent moons.
• These irregularly shaped cells can get stuck
in small blood vessels, which can slow or
block blood flow and oxygen to parts of the
body.
33. • 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.
34.
35. GENETICS
• The change in cell structure arises from a change in the structure of
hemoglobin.
• A single change in an amino acid causes hemoglobin to aggregate.
• Sickle cell disease is caused by a mutation in the hemoglobin-Beta gene
found on chromosome 11.
36.
37.
38. • RBCs containing HbS have a shorter lifespan
Normally 20 days
Chronic state of anemia
Symptoms:
They vary from person to person and change over time, include:
1. Anemia. Sickle cells break apart easily and die, leaving you without
enough red blood cells. Red blood cells usually live for about 120 days
before they need to be replaced. But sickle cells usually die in 10 to
20days, leaving a shortage of red blood cells (anemia) causing fatigue.
39. 2. Episodes of pain. Periodic episodes of pain, called crises, are a major
symptom of sickle cell anemia.
Pain develops when sickle-shaped red blood cells block blood flow through
tiny blood vessels to your chest, abdomen and
joints.
3. Stroke, Acute chest syndrome, Pulmonary hypertension, organ
damage, blindness.
Treatments might include medications to reduce pain and prevent
complications, and blood transfusions, as well as a bone marrow transplant.
41. • Huntington's disease is caused by an inherited defect in a single gene.
• Huntington's disease is an autosomal dominant disorder, which means that a
person needs only one copy of the defective gene to develop the disorder.
• With the exception of genes on the sex chromosomes, a person inherits two
copies of every gene — one copy from each parent.
• A parent with a defective gene could pass along the defective copy of the gene
or the healthy copy.
• Each child in the family, therefore, has a 50% chance of inheriting the gene that
causes the genetic disorder
42.
43. CAUSE
• The HTT mutation that causes Huntington disease involves a DNA segment known as a CAG
trinucleotide repeat.
• This segment is made up of a series of three DNA building blocks (cytosine, adenine, and
guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 10 to 35
times within the gene.
• In people with Huntington disease, the CAG segment is repeated 36 to more than 120 times.
• An increase in the size of the CAG segment leads to the production of an abnormally long
version of the huntingtin protein. The elongated protein is cut into smaller, toxic fragments that
bind together and accumulate in neurons, disrupting the normal functions of these cells. The
dysfunction and eventual death of neurons in certain areas of the brain underlie the signs and
symptoms of Huntington disease.
44.
45. • The disease causes progressive degeneration of neurons in the brain.
• Signs and symptoms usually develop between ages 35 to 44 years and may
include uncontrolled movements, loss of intellectual abilities, and various
emotional and psychiatric problems.
• People with HD usually live for about 15 to 20 years after the condition begins.
• It is caused by changes (mutations) in the HTT gene and is inherited in an
autosomal dominant manner.
46. Symptoms:
• Behavioral disturbances, Clumsiness, Moodiness, Irritability, Paranoia,
Apathy, Anxiety
• Hallucinations, Abnormal eye movements, Depression, Involuntary
movements
• Trouble with balance and walking
• Chorea with twisting and writhing motions
• Slow reaction time
• General weakness
• Weight loss
• Speech difficulties
• Stubbornness etc.
47. Familial hypercholesterolemia
• Familial hypercholesterolemia is a disorder that is passed down through families. It causes LDL
(bad) cholesterol level to be very high.
• Familial hypercholesterolemia is a genetic disorder. It is caused by a defect on chromosome 19.
• The defect makes the body unable to remove low density lipoprotein (LDL, or bad) cholesterol
from the blood.
• As a result, cholesterol accumulates in the bloodstream and can ultimately build up in the walls of
the arteries.
• Cholesterol build up in the artery wall is called hardening of the arteries, or atherosclerosis, and can
lead to problems such as heart attacks and strokes in young adults and even children.
• The condition is typically passed down through families in an autosomal dominant manner.
49. DEFECTS IN METABOLISM OF AMINO ACIDS :
PHENYLKETONURIA (PKU)
• Phenylalanine is an essential amino acid.
• Dietary phenylalanine not utilized for protein synthesis is normally degraded by
way of the Tyrosine pathway.
• (PKU) is an autosomal recessive metabolic genetic disorder characterized by a
deficiency in the hepatic enzyme phenylalanine hydroxylase (PAH).
• This enzyme is necessary to metabolize the phenylalanine (Phe) to the tyrosine.
50. • When PAH isdeficient, phenylalanine accumulates and is converted into
phenylpyruvate, which is detected in the urine.
• It can cause problems with brain development, leading to progressive mental
retardation, brain damage, and seizures.
• Optimal treatment involves lowering blood (Phe) levels to a safe range and
monitoring diet and cognitive development.
• The brain is the main organ affected by hyperphenylalaninemia.
51. Alkaptonuria
• Alkaptonuria is inherited as an autosomal recessive trait.
• Alkaptonuria is an inherited condition that causes urine to turn black when exposed to
air.
• This blue-black pigmentation usually appears after age 30. People with alkaptonuria
typically develop arthritis, particularly in the spine and large joints, beginning in early
adulthood.
• Mutations in the HGD gene (homogentisate 1,2-dioxygenasegene)cause alkaptonuria.
• The HGD gene provides instructions for making an enzyme called homogentisate
oxidase.
52. • This enzyme helps break down the amino acids phenylalanine and tyrosine, which are
important building blocks of proteins.
• Mutations in the HGD gene impair the enzyme's role in this process.
• As a result phenylalanine and tyrosine accumulates in the body.
• Although homogentisic acid is rapidly cleared from the body by the kidneys, it also
slowly accumulates in the various tissues of the body, especially connective tissue
such as cartilage.
• Long-term, chronic accumulation of homogentisic acid eventually weakens and
damages affected tissue and leads to many of the characteristic symptoms of
alkaptonuria.
53.
54. ALBINISM
• Albinism is a group of inherited disorders that results in little or no production of the pigment
melanin.
• Melanin also plays a role in the development of certain optical nerves, so all forms of
albinism cause problems with the development and function of the eyes.
• People with albinism often have white or very light blonde hair, although some have brown or
ginger hair. The exact colour depends on how much melanin their body produces.
55. • Albinism is caused by mutations and most types are inherited in an autosomal recessive manner.
Eye problems
• The reduced amount of melanin can cause eye problems. This is because melanin is involved in the
development of the retina, the thin layer of cells at the back of the eye.
• Possible eye problems linked to albinism include:
• Poor eyesight – either short-sightedness or long-sightedness, and low vision (sight loss that cannot be
corrected)
• Astigmatism – where the cornea (clear layer at the front of the eye) is not perfectly curved or the lens
is an abnormal shape, causing blurred vision
• Potophobia – where the eyes are sensitive to light
• Squint – where the eyes point in different directions
