There are several classes of hereditary diseases: 1) Diseases of simple genetic architecture are caused by a single gene and follow recognizable patterns of inheritance. They are usually rare. 2) Diseases of complex genetic architecture do not have clear patterns of inheritance and are influenced by multiple genes and the environment. They are more common. 3) Genetic disorders can be caused by abnormalities in chromosomes, single genes, or a combination of genetic and environmental factors. They result in conditions like cystic fibrosis, sickle cell anemia, muscular dystrophy, and Down syndrome. Changes in chromosome number, structure, or sex chromosomes can also cause genetic disorders.

1. Hereditary diseases

2. CLASSES OF HUMAN
GENETIC DISEASE

3. Diseases of Simple Genetic
Architecture
– Can tell how trait is passed in a family: follows
a recognizable pattern
– One gene per family
– Often called Mendelian disease
– Usually quite rare in population
– “Causative” gene

4. Diseases of Complex Genetic
Architecture
– No clear pattern of inheritance
– Moderate to strong evidence of being
inherited
– Common in population: cancer, heart disease,
dementia etc.
– Involves many genes or genes and
environment
– “Susceptibility” genes

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6. Classification of genetic disorders
• Multifactorial
• Single gene
• Chromosomal
• Mitochondrial
• Somatic mutations (cancer)

7. GENETIC ENVIRONMENTAL
Duchenne
muscular dystrophy
Haemophilia
Osteogenesis imperfecta
Club foot
Pyloric stenosis
Dislocation of hip
Peptic ulcer
Diabetes
Tuberculosis
Phenylketonuria
Galactosaemia
Spina bifida
Ischaemic heart disease
Ankylosing spondylitis
Scurvy
The contributions of genetic and environmental
factors to human diseases
Rare
Genetics simple
Unifactorial
High recurrence rate
Common
Genetics complex
Multifactorial
Low recurrence rate

8. What is a genetic disorder?
• A genetic disorder is a condition caused
by any abnormality in a person’s genes or
chromosomes
• Genetic disorders have 2 main causes

9. Cause 1
• An error during meiosis causes a sperm
cell or an egg cell to have some defect.
• If one of these gametes is involved in
fertilization, it usually results in
miscarriage, but in a few cases, a baby
will develop and be carried to term with a
genetic disorder

10. Nondisjunction Causes:
• Aneuploidy: cells that have too many or
too few chromosomes are aneuploid.
– Monosomy: only 1 of a pair present
– Trisomy: 3 instead of 2 present

11. Cause 2
• A defective gene present in one or both of
the parents is inherited directly by the child
causing a disorder
• These kinds of disorders are call
hereditary diseases and follow the same
rules of inheritance as other human traits

12. Incidence of Genetic Abnormalities
• Maternal Age
– At 25 years, 17% of eggs may have
chromosomal abnormalities. At 40 years, up
to 74% may contain abnormalities.
• Spontaneous Abortion (Miscarriage)
– Two-thirds of all pregnancies are lost. These
miscarriages are called spontaneous
abortions.
– Genetic mutation causes an estimated 60% of
these spontaneous abortions.

13. Family Pedigrees

14. Categories of genetic diseases.
Genetic diseases can largely be divided into three categories:
A.Chromosomal disorders - those that are caused by
numerical or structural abnormalities of thechromosomes,
e.g. Down syndrome, Turner syndrome.
B. Single gene disorders - those that are caused by defects
of individual genes, e.g. thalassaemia,haemophilia. Gene
defects are not detectable by chromosome analysis.
C.Multifactorial disorders - those that are the result of the
combined effect of genetic factors andenvironmental factors,
e.g. diabetes mellitus, hypertension, psychiatricdiseases and
cancer.

15. Hereditary Diseases Caused by
Dominant Genes
• Only one copy of the gene (from either
parent) is needed for a person to have the
disease
• A person with a dominant hereditary
disease usually has at least one affected
parent
• Parents have a 50% chance of passing
these types of diseases to children

16. Autosomal Dominant Disorders
• Neurofibromatosis (NF)
– Could be “Elephant Man’s” disorder
– As mild as tan spots on skin
– Could cause severe deformities, tumors, even
death
– 1 in 3000 newborns
– Mutation on chromosome 17

17. Huntington’s Disease
– Brain cells degenerate, causing involuntary
muscle jerks, slurred speach, loss of balance,
mood swings, memory loss, incapacitation
– Progressive: eventually causes death
– Onset: 35-45 years old
– Repeated sequences of AGC on chromosome
4
– The disease is also known as Huntington's
chorea. Chorea means "dance-like
movements" and refers to the uncontrolled
motions often associated with the disease.

19. Hereditary Diseases Caused by
Recessive Genes
• Two copies of the defective gene must be
inherited (one from each parent)
• Affected persons usually have two non-
affected parents who are carriers
• Two carrier parents have a 25% chance of
having a child with the disease

20. Autosomal Recessive Disorders
• Cystic Fibrosis (CF)
– Mutation on chromosome 7
– Thick mucous develops in lungs and digestive
tract
– Difficulty breathing & lung infections
– Most common lethal genetic disorder
– 1 in 25 is a carrier
– 1 in 2500 has disorder

22. Tay Sachs Disease
– Fatty substance builds up in neurons
– Gradual paralysis and loss of nervous
function by age 4-5
– Single defective enzyme
– Heterozygote carriers (Hh) do not have
disorder, but are resistant to Tuberculosis
– Especially common in Jewish population
(central and eastern European descent),
– up to 11% are carriers

24. PKU (Phenylketonuria)
– Can’t break down amino acid phenylalanine
(missing critical enzyme)
– Phenylalanine builds up and interferes with
nervous system leading to mental retardation
and even death
– Early screening  phenylalanine restricted
diet for children with disorder

26. Sickle-Cell Anemia
– Abnormality in hemoglobin
– Cells become sickle-shaped and clog blood
vessels (painful)
– Causes poor circulation, jaundice, anemia,
and hemorrhaging
– Heterozygote carriers (Hh) do not have
disorder and are resistant to malaria
– 8-10% of Africans (or descendants) are
carriers

28. Hereditary Disease Caused by
Sex-Linked Recessive Genes
• Caused by defective genes carried on the
X chromosome
• Males affected more than women
• Males inherit one defective gene on X
from mother to have disorder
• Females only affected if they inherit 2
defective genes (one from each parent)

29. • Color blindness (3 types – Red/Green
most common)

30. Color Blindness
In humans, color vision receptors in the
retina are three different classes of cone
cells.
• Only one type of pigment is present in each
class of cone cell.
–The allele for blue-sensitive is
autosomal, but the red- and green-
sensitive proteins are on the X
chromosome.

31. Hemophilia
• Caused by the inheritance of
one recessive gene on the X
(males) or two recessive
genes on both X’s (females)
• Affects blood – blood does
not clot
• Leads to severely increased
risk of bleeding from common
injuries
• Potentially fatal
• Occurs more frequently in males
1 in 1500 males

32. Muscular dystrophy causes the muscles in the
body to become very weak.
The muscles break down and are replaced with
fatty deposits over time.
Other health problems commonly associated with
muscular dystrophy include the following:
•Heart problems
•Scoliosis. A lateral, or sideways, curvature and
rotation of the back bones (vertebrae), giving the
appearance that the person is leaning to one side
.
•Obesity
Muscular Dystrophy
(MD)

34. Changes in Chromosome
Number
• Monosomy and Trisomy
– Monosomy (2n - 1) occurs when an individual
has only one of a particular type of
chromosome.
– Trisomy (2n + 1) occurs when an individual
has three of a particular type of chromosome.

35. Down Syndrome
• Caused by Trisomy 21
• Symptoms:
– Mental retardation
– Flattened face
– Sparse, straight hair
– Short stature
– High risk of cardiac anomalies, leukemia,
cataracts, and digestive blockages
– Average life expectancy: 55 years (much
longer than it used to be even just recently)

36. Trisomy21 (Down Syndrome)
• The most common chromosomal disorder
with incidence of 1:700
• 95% trisomy21; 4% Robertsonian
translocation involving the long arm of 21;
1% mosaic
• High correlation between maternal age
and meiotic nondisjunction leading to
trisomy21

37. Edward Syndrome
• Caused by Trisomy 18
• Symptoms:
– Mental and physical retardation
– Skull and facial abnormalities
– Defects in all organ systems
– Poor muscle tone
– Average life expectancy: 2-4 months

38. Patau Syndrome
• Caused by Trisomy 13
• Symptoms:
– Mental and physical retardation
– Skull and facial abnormalities
– Defects in all organ systems
– Cleft lip & large triangular nose
– Extra digits
– Average life expectancy: 6 months (but ½ die
in the first month)

39. Changes in Sex Chromosome
Number
• An abnormal sex chromosome number is
the result of inheriting too many or too few
X or Y chromosomes.
– Nondisjunction during oogenesis or
spermatogenesis.

41. Sex Chromosome Abnormalities

42. Turner syndrome (45, XO)
• 1:3000 female births
• Extensive karyotype heterogeneity with question
about existence of pure monosomy X (99% of
45, X eggs are non-viable)
• Short stature, webbing of the neck,
cardiovascular abnormalities, lack of secondary
sex characteristics, streak ovaries (accelerated
loss of oocytes), sexually underdeveloped

43. Klinefelter syndrome
(47, XXY)
• 1:850 male births
• Rarely diagnosed before puberty
• Tall stature, hypogonadism, lack of secondary
male characteristics, gynecomastia
• The principal cause of male infertility due to
reduced spermatogenesis
• Reduced sexual maturity, secondary sexual
characteristics (breast swelling), no sperm
production

44. TURNER SYNDROME X0
TURNER SYNDROME XO KLINEFELTER XXY

47. • Triple X Syndrome (XXX – female)
– 1 in 1500
– Slight IQ reduction, menstrual irregularities
• Jacob Syndrome (XYY – male)
– Incidence unknown (lack of diagnosis)
– Tall, acne issues, speech/reading problems
– Disproportionate number incarcerated
– 96% are normal (most don’t realize they have
this condition)
Sex Chromosome Abnormalities

54. Changes in Chromosome
Structure
• Deletion
– End of a chromosome breaks off, or two
simultaneous breaks lead to loss of an
internal segment.
• Translocation
– Movement of a chromosome segment from
one chromosome to another, non-
homologous chromosome.

55. WILLIAMS SYNDROME

56. Williams Syndrome
• Delayed speech
• Developmental delay
• Easily distracted, attention deficit disorder (ADD)
• Learning disorders
• Mild to moderate mental retardation
• Personality traits including being very friendly, trusting
strangers, fearing loud sounds or physical contact, and
being interested in music
• Short compared to the rest of the person’s family
• Sunken chest (pectus excavatum)
• Unusual appearance of the face
– Flattened nasal bridge with small upturned nose
– Partially missing teeth

57. Cri du Chat Syndrome
(cry of the cat)
•Deletion on part of chromosome 5
•It gets its name from the tell-tale mew of the infants born with the
disorder.
•problems with the larynx and nervous system.
•The affected child will often drool excessively, but have difficulty
swallowing and sucking, causing feeding problems.
•A child born with the disorder will often have a small birth weight and
a poor growth rate.
• As the child grows, it will show signs of mental and physical
retardation and behavioral problems such as aggression,
hyperactivity, and repetition of movement.
•They will most likely also have facial deformities, but these may
change over time.

59. ALAGILLE SYNDROME

61. Single-Gene Disorders
Structural proteins
• Osteogenesis imperfecta and Ehlers-
Danlos(collagens);
• Marfan syndrome (fibrillin);
• Duchenne and Becker muscular
dystrophies (dystrophin)

63. Enzymes and inhibitors
• Lysosomalstorage diseases;
• SCID (adenosine deaminase);
• PKU (phenylalanine hydroxylase);
• Alpha-1 antitrypsin deficiency

66. Receptors
• Familial hypercholesterolemia (LDL
receptor)

67. Familial Hypercholesterolemia
(FH)
• The most frequent Mendelian disorder
• Heterozygotes, representing 1:500, have
2-3x elevation of cholesterol levels with
xanthomasand premature atherosclerosis
• Homozygotes develop extensive
xanthomas, as well as coronary, cerebral
and peripheral vascular disease at an
early age, and may develop MI before the
age of 20

69. Cell growth regulation
• Neurofibromatosis type I (neurofibromin);
• Hereditary retinoblastoma (Rb)

70. Neurofibromatosis Type 1 (NF1)
• Multiple neurofibromas; pigmented skin lesions;
pigmented iris hamartomas(Lischnodules); plus a variety
of other abnormalities
• Incidence of at least 1:3000
• Autosomal dominant trait with complete penetrance
• ~50% of cases are “sporadic”
• Mutation rate 1/10,000 gametes; the highest observed in
humans
• Neurofibrominmapped to 17q11.2 down-regulates the
function of p21rasoncoprotein

72. Transporters
• Cystic fibrosis (CFTR);
• Sickle cell disease (Hb);
• Thalassemias(Hb)

73. – Repeated sequences of CCG on X
chromosome
– Normal = 6-50 copies
– Carrier (males) = 50-230 copies
– Disorder = more than 230 copies
– Causes mental retardation (2nd
behind only
Down Syndrome)
Fragile X

75. LARGE NUMBER
OF TRIPLET
REPEATS OF CGG
AT FRAGILE SITE
ON X
CHROMOSOME

76. Mitochondrial Inheritance:
Mitochondrias come from ancestor anareobic bacterias ;
they have their own DNA.
We then have extranuclear DNA in our cells.
MITOCHONDRIAL DNA :
1.Circular DNA of 16 kb for which the sequence is entirely known.
2.37 genes code for 13 proteins, ribosomal RNA and transfer
RNA.
3.The genetic code is different from the universal code (1): Mito
Univ UGA Trp STOP AUA Met Ile AGA/AGG STOP Arg.
4.Mitochondria are present in the ovocyte (in large number).
5. Results in > non mendelian inheritance: strictly maternal
inheritance.
6.There are hereditary diseases due to mutant mitochondrial
genes.

80. A mitochondrial gene
disease is transmitted :
• solely by women.
• to all her descents.
• Often the genetic defect is not present in all‐
but in a fraction only of mitochondria
transmitted to the next generation; then
according to the number of gene mutations in
mitochondria.
• variable expressivity

82. Mitochondrial cytopathies are often
deleterious with a pleiotropic
symptomatology ( multiple), since the
deficit involves several organs:
Pearson syndrome:
•exocrine pancreatic insufficiency,
•medullar insufficiency/ myelodysplasia,
•muscular deficit,
• hepatic, renal and gastro intestinal
diseases.
•.

83. Mitochondrial myopathies
The term refers to a group of muscle disorders, including:
• Kearns-Sayre syndrome (KSS)
•Leigh’s syndrome Mitochondrial Depletion syndrome (MDS)
• Mitochondrial Encephalomyopathy Lactic Acidosis and
Stroke-like episodes (MELAS)
•Myoclonic epilepsy with Ragged Red Fibers (MERRG)
•Mitochondrial neurogastrointestinal encephalopathy
syndrome (MNGIE) Neuropathy, Ataxia, and Retinitis
Pigmentosa (NARP)
• Pearson syndrome Chronic Progressive External
Opthalmoplegia (CPEO)

85. Multifactorial and polygenic
disorders
• Genetic disorders may also be complex, multifactorial or polygenic,
this means that they are likely associated with the effects of multiple
genes in combination with life style and environmental factors
• Complex disorders are also difficult to study and treat because the
specific factors that cause most of these disorders have not yet
been identified.
• Although complex disorders often cluster in families, they do not
have a clear cut pattern of inheritance.‐
• This makes it difficult to determine a person’s risk of inheriting or
passing on these disorders. On a pedigree, polygenic diseases do
tend to “run in families”, but the inheritance does not fit simple
patterns as with Mendelian diseases.

86. examples
• heart disease,
• hypertension,
• diabetes,
• obesity,
• cancers.

88. HOW CAN GENETIC
DISORDERS BE
DETECTED?

93. Genetic Testing
• Amniocentesis and Chronic Villi Sampling
– Sample of amniotic fluid or placenta
• Karyotyping
– Taking a picture of the chromosomes in a cell