Genetics

1. By : Gan Quan Fu, PT,
MSc Human Anatomy (Batch 3)

2.  Introduction
 Classification of Genetic Disorder
 Definition & Prevalence
 Autosomal Anomalies
 Numeric Chromosomal Anomalies
 Structural Chromosomal Anomalies
 Sex Chromosome Anomalies
 Numeric Chromosomal Anomalies
 Structural Chromosomal Anomalies
 Important definitions in Genetics

3. Classification of Genetic
Disorder
Single gene
disorders
Chromosomal
Disorder
Autosomal
Numeric Structural
Sex
Chromosome
Numeric Structural
Multifactorial
Disorder
Acquired
Somatic Genetic
Disease

4.  Chromosomal Anomalies = Missing, extra, or
irregular portion of chromosomal DNA.
 Most foetus with some chromosomal
abnormality do not survive.
 Affects approximately 1 out of 200 of new-
borns.
 Karyotype = Full set of chromosomes from an
individual. (Chromosomal Anomalies can be
detected via Karyotype Testing.)
 Abnormalities depends on type of chromosome
affected due to non-disjunction chromosomes.

6. Chromosome affected
Autosomes
Numeric
Autosomal
Trisomies
Autosomal
Monosomy
Structural
Single
Chromosome
Disorder
Two
Chromosome
Disorder
Sex Chromosomes
Numeric Structural

7. Monosomy
Trisomies

8. Autosomal Anomalies (Numeric)
Monosomy
Single copy of an
autosome.
Lethal in early
pregnancy.
Trisomies
Patau Syndrome
(47 + 13)
Edwards Syndrome
(47 + 18)
Down Syndrome
(47 + 21)

10.  An additional chromosome 13 resulting
from nondisjunction during meiosis.
 Incidence = 1 in 10,000 -20,000 live
births.
 More than 80% die within the first year of
life.
 Anomalies can be seen on:
 Nervous & Optic System
 Musculoskeletal & Cutaneous
 Urogenital & Cardiovascular System

11.  Intellectual disability and motor disorder
 Microcephaly
 Holoprosencephaly (failure of the forebrain to
divide properly).
 Structural eye defect:
 Microphthalmia
 Peters anomaly (a type of eye abnormality)
 Cataract
 Iris and/or fundus (coloboma)
 Retinal dysplasia or retinal detachment
 Sensory nystagmus
 Cortical visual loss
 Optic nerve hypoplasia
 Meningomyelocele (a spinal defect)

12.  Polydactyly (extra digits)
 Cyclopia
 Proboscis
 Congenital trigger digits
 Low-set ears
 Prominent heel
 Deformed feet known as rocker-bottom feet
 Omphalocele (abdominal defect)
 Abnormal palm pattern
 Overlapping of fingers over thumb
 Cutis aplasia (missing portion of the skin/hair)
 Cleft palate

13.  Urogenital
 Abnormal genitalia
 Kidney defects
 Cardiovascular
 Heart defects (ventricular septal defect &
Patent Ductus Arteriosus)
 Dextrocardia
 Single umbilical artery

15. A. Midline defect with
cleft lip & palate.
B. Clenched hand with
overlapping fingers.
C. Postaxial polydactyly.
D.Equinovarus deformity.
E. Punched out aplasia
cutis scalp lesions.

16.  An additional chromosome 18 resulting from
nondisjunction during meiosis.
 Incidence =1 in 6000 - 8000 live birth.
 Majority of fetuses with this syndrome die
before birth; >90% dead in 1st year.
 80% affected were females.

17.  Kidney malformations
 Structural heart defects at birth
 Ventricular septal defect
 Atrial septal defect
 Patent ductus arteriosus
 Omphalocele (Intestines protruding outside the body)
 Esophageal atresia
 Intellectual disability
 Developmental delays
 Growth deficiency
 Feeding difficulties
 Breathing difficulties
 Arthrogryposis (a muscle disorder that causes multiple
joint contractures at birth)

18.  Small head (microcephaly) accompanied by a prominent
back portion of the head (occiput),
 Low-set, malformed ears,
 Abnormally small jaw (micrognathia),
 Cleft lip/cleft palate,
 Upturned nose,
 Narrow eyelid folds (palpebral fissures),
 Widely spaced eyes (ocular hypertelorism),
 Drooping of the upper eyelids (ptosis),
 A short breast bone,
 Clenched hands
 Choroid plexus cysts
 Underdeveloped thumbs and/or nails
 Absent radius
 Webbing of the second and third toes, clubfoot or rocker
bottom feet
 Males will have undescended testicles.

22.  An additional chromosome 21 resulting from
nondisjunction during meiosis. (*Extra
chromosome 21 in every cell of the body)
 John Langdon Down (the British physician)
who described the syndrome in 1866.
 Karyotype = 47,XX+21 or 47,XY+21

23. Characteristics Percentage Characteristics Percentage
Mental impairment 99% Abnormal teeth 60%
Stunted growth 90% Slanted eyes 60%
Umbilical hernia 90% Shortened hands 60%
Increased skin back
of neck
80% Short neck 60%
Low muscle tone 80%
Obstructive sleep
apnea
60%
Narrow roof of
mouth
76% Bent fifth finger tip 57%
Flat head 75%
Brushfield spots in
the iris
56%
Flexible ligaments 75%
Single transverse
palmar crease
53%
Large tongue 75% Protruding tongue 47%
Abnormal outer ears 70%
Congenital heart
disease
40%
Flattened nose 68% Strabismus ~35%
Separation of first
and second toes
68%
Undescended
testicles
20%

27.  Can happen in a chromosome itself,
the other is not required.
Deletion
(Genetic material
missing)
Duplication
(Genetic material
present twice)
Inversion
(Genetic material is
“flipped”)

28.  Need 2 chromosomes to occur these
processes.
Insertion
(Genetic material is added from
another chromosome)
Translocation
(Material is swapped(exchanged)
with another chromosome)

29.  Name is based on the infant’s cry. (high-
pitched and sounds like a cat.)
 Incidence =1 in 216,000 birth
 Normal 46 chromosomes but, missing a piece
of chromosome number 5.
 Most cases are believed to occur during the
development of the egg or sperm, small
number of cases occur when a parent passes
a different, rearranged form of the
chromosome to their child.

30.  Cry is high pitched and similar to that of a
meowing kitten.
 Moon-shaped face
 Malformed larynx
 Difficulty swallowing and sucking (Feeding
Problem).
 Low birth weight and poor growth.
 Severe cognitive, speech, and motor delays,
mental retardation
 Behavioural problems such as hyperactivity,
aggression, and repetitive movements.
 Excessive drooling(ptyalism)

34. Chromosome affected
Autosomes
Numeric Structural
Sex
Chromosomes
Numeric
Autosomal
Trisomies
Autosomal
Monosomy
Structural
X-link
Dorminant
X-link
Recessive

35. Sex Chromosome Anomalies
(Numeric)
Monosomy
Turner’s
syndrome
(45,X0)
Trisomies
Klinefelter's
syndrome
(47,XXY)
Jacob’s
syndrome
(47,XYY)
Triple x
syndrome
(47,XXX)

36.  Sex chromosomal monosomy(45, XO)
 99% of foetuses with Turner syndrome result
in spontaneous termination during the first
trimester.
 Incidence = 1 in 2000-5000.

37.  Short stature
 Skeletal disorders (osteoporosis which may lead
to scoliosis)
 Webbed neck(due to cystic hygroma)
 Broad shoulders
 Broad chest (shield chest), widely spaced nipples
 No/Poor breast development
 Narrow hips (High waist-to-hip ratio: hips are not
much bigger than waist)
 Lymphedema of hands and feet
 Shortened metacarpal IV
 Cubitus valgus

38.  Underdeveloped ovaries(streak gonads,
hence this syndrome also called ovarian
dysgenesis)
 Sterile, lack expected secondary sex
characteristics
 Amenorrhoea(No menstruation)
 Cardiovascular problems (Coarctation of the
aorta, Bicuspid aortic valve)
 Horse shoe kidney
 Thyroid problems (hypothyroidism
specifically Hashimoto's thyroiditis).

41.  XXY Males
 Disorder occurring due to nondisjunction of
the X chromosome during Meiosis.
 Extra X chromosome is nondisjunction during
meiosis II of the germ cell in the female.
 Occur when sister chromatids on the X sex
chromosome fail to separate.
 XX ovum produced and when fertilized with a Y-
sperm it yields XXY offspring.
Also occurs X and Y sex chromosomes fail to
separate, producing a sperm with an X and Y
chromosome & fertilize with normal X ovum
produces XXY offspring.
 Incidence = 1 in 500 live male births.

43.  48, XXYY (male) syndrome
 Incidence = 1 in 18,000–40,000 births
 48,XXXY
 Incidence = Extremely rare

44.  Childhood
 Weaker muscles and reduced strength.
 Puberty (features become more prominent due to
hypogonadism (less amount of testosterone produced):
 Rounded body type
 Broader hips
 Little body hair is present
 Gynecomastia (increased breast tissue)
 Microorchidism (i.e. small testicles)
 Azospermia leading to infertility
 Micropenis
 Tall stature
 IQ is normal

47.  Characterized by the presence of an
additional Y chromosome.
 Incidence = 1 in 1,800 births
 Features Present:
 Normal physically
 Normal mentally
 Increase in testosterone
 More aggressive
 Normal lifespan
 There are article which claims that those
with Jacob’s Syndrome are more prone in
committing crime.

49.  Characterized by the presence of an additional X
chromosome.
 When an XX ovum fertilizes with X- sperm.
 Incidence = 1 in 1,000 birth
 Features Present
 Normal physically, Sometimes taller.
 Normal mentally, Increase risk of retardation
and learning difficulties.
 Fertile.

51. Genotype Gender Syndrome Physical Traits
XY Male -
XXY
XXYY
XXXY
Male Klinefelter’s
Syndrome
sterility, small testicles,
breast enlargement
XYY Male XYY or Jacob’s
Syndrome
normal male traits
XX Female -
XO Female Turner Syndrome sex organs don’t mature
at adolescence, sterility,
short stature
XXX Female Triple X tall stature, learning
disabilities, limited fertility

53. Sex Chromosome Anomalies
(Structural)
Y-Linked
Disease
Very Rare
X-Linked
Disease
X-Linked
Dominant
X-Linked
Recessive

54.  Also known as ‘holandric inheritance’.
 Determination of a phenotypic trait by an
allele (or gene) on the Y chromosome.
 Pass from father to son with no
interchromosomal genetic recombination
 Very rare.
 Deletion (missing genetic materials) in Y-
gene is a frequent genetic cause of male
infertility.
 Having hairy ears was once thought to be a
Y-linked trait in humans, but that hypothesis
has been discredited.

55.  Single gene disorders that reflect the presence
of defective genes on the X chromosome.
 Show inheritance patterns that differ from
autosomal diseases.
 Male have one X chromosome + a Y chromosome
while females have 2 X chromosome, they show
different patterns of inheritance and severity of
manifestation. (There are both dominant and
recessive X-linked diseases, also there are some
characteristics that are common to X-linked
disorders in general).
 Males are never carriers, if they have a mutated
gene on the X chromosome, it will be expressed.
 Males are termed hemizygous for genes on the X
chromosome.

56.  Expressed in females when only a single copy of the mutated
gene is present.
 Very few diseases have been identified:
 Alport syndrome
 Nephrogenic Diabetes Insipidus
 Hypophosphatemic rickets or vitamin D resistant rickets
(leading to low serum phosphorus & skeletal abnormalities)
 Never passed from father to son.
 Affected males produce only affected females. (An affected male
only has one X chromosome to pass on to his daughters.
 Affected females produces 50% normal and 50% affected
offspring. (Heterozygous).
 Males are usually more severely affected than females. Some X-
linked traits may even be lethal.
 Females are more likely affected. (They have 2x increase risk to
inherit the mutated allele, since they have 2X chromosomes)

59.  Inherited, heterogeneous disorders involving
basement membranes of kidney, frequently affecting
the cochlea and eyes.
 Clinical Manifestation:
 Renal
 Hematuria
 Proteinuria
 Hypertension with edema and nephrotic syndrome at
later stage.
 Hearing
 Sensorineural deafness (90% are deaf by age of 40 years)
 Ocular
 Dot-and-fleck retinopathy
 Leiomyomatosis
 Diffuse leiomyomatosis of the esophagus and
tracheobronchial tree

61.  Occurs when the kidneys cannot concentrate
urine normally resulting excretion of large
amount of dilute urine. *Kidney tubules do not
respond to Antidiuretic Hormone (ADH).
 Very Rare
 Symptoms
 Intense or uncontrollable thirst, and crave
ice water.
 Produce large amounts of urine (usually
more than 3 liters, and up to 15 liters per
day.)
 Easily dehydrated

62.  Form of rickets characterized by low serum
phosphate levels.
 Resistance to treatment with ultraviolet
radiation or vitamin D ingestion.
 Incidence = 1 in 20,000 newborns
 Symptoms:
 Short stature
 Associated with this condition is disproportionate,
resulting from deformity and growth retardation of the
lower extremities.
 Bow Legged and deformities associated with
bones
 Bone Pain and Joint Pain

64.  Hereditary pattern which a recessive gene in X
chromosome results in:
 Male : Manifestation of characteristics
 Female : Carrier (Usually)
 Males are more likely affected, they only need
one copy of mutant allele to express phenotype.
 Female must have 2 copies of the mutant allele
in order for the mutant phenotype to develop.
 Female with 1 copy of the mutant allele is only a
carrier.
 Disorders are:
 Colour blindness
 Duchenne Muscular Dystrophy
 Hemophilia

66.  Also known as colour vision deficiency (CVD).
 Trouble seeing
 Red
 Green
 Blue
 Mix of colours mentioned above.
 Rarely that a person sees no color at all.
 Three types of cone cells in eye (each type
senses either red, green, or blue light most
concentrated in macula). Individuals with colour
blindness do not have these cone cells.
 Incidence = Approximately 1 in 12 men (8%); 1 in
200 women

69.  Form of muscular dystrophy (muscle
weakness and loss of muscle tissues) which
worsens quickly.
 Caused by a defective gene for dystrophin (A
type of protein in muscles).
 Incidence = 1 in 3,600 male infants

70.  Usually appear before age 6 and may appear as
early as infancy.
 Include:
 Fatigue
 Learning difficulties (IQ can be below 75)
 Intellectual disability
 Muscle weakness:
 Begins in the legs and pelvis less severe in the arms,
neck, and other areas of the body
 Problems with motor skills (running, hopping, jumping)
 Frequent falls
 Trouble getting up from a lying position or climbing stairs
 Weakness quickly gets worse
 Progressive difficulty walking:
 Ability to walk may be lost by age 12
 Breathing difficulties and heart disease usually start
by age 20

72.  Blood fails to clot normally
 Lacking a blood clotting factor VIII
(antihemophilic globulin, AHG), IX (Chrismas
Factor).
 Bleeding from even minor cuts
 Incidence = 1,500 newborn males.
 Hemophilia A = Lack of clotting factor VIII.
75% occurrence.
 Hemophilia B = "Christmas Disease" is a
defect in clotting factor IX.
 Transfusions of fresh whole blood or plasma
or factor to control bleeding

76.  Also known as Martin-Bell syndrome; Marker X
syndrome.
 Some consider this syndrome as X-linked
dorminant, some consider this as X-linked
recessive which some claims this to be not under
X-linked dorminant or recessive.
 Genetic condition involving changes in the long
arm of the X chromosome.
 Characterized by mental retardation.
 Fragile area on X chromosome tends to repeat
bits of the genetic code. (*More repeats, the
more likely there is to be a problem.)
 Male and female can both be affected.
 Male have only one X chromosome, single fragile
X more likely to affect them more severely.

77.  Family history of fragile X syndrome,
especially a male relative
 Mental retardation
 Large testicles (macro-orchidism)
 Large size
 Tendency to avoid eye contact
 Hyperactive behaviour
 Large forehead and/or ears with a prominent
jaw

81.  Aneuploidy = Addition or loss of one (rarely two)
chromosome.
 Trisomy = 3 copies of a chromosome, (2n+1)
 Tetrasomy = 4 copies of a chromosome, (2n+2)etc
 Monosomy = 1 member of a chromosome pair missing, (2n-1)
that is only single copy of a chromosome is present.
 Euploidy = Normal condition, where the genotype consists
of complete two sets of chromosomes (23+23 or 2n).
 Genotype = Genetic make up of cell.
 Karyotype = Number and appearance of chromosome in a
nucleus.
 Non disjunction = Incorrect separation of chromosomes or
sister chromatids during meiosis.
 Phenotype = Characteristics of an Organism
 Polyploidy = Entire extra set of chromosomes present, [can
be triploidy(3n= 69 chromosomes),tetraploidy(4n=92
chromosomes) etc.]