GENETIKA MANUSIA

TEAM TEACHING BIOLOGI FARMASI

FAKULTAS FARMASI
UNIKA WIDYA MANDALA SURABAYA
DNA
 TOPICS
• DNA Sequencing
• Single Nucleotide Polymorphism (SNP)
• Dosage Compensation
• Incomplete Dominance in Human
Hypercholesterolemia
• Constructing Genogram
• Recessive and dominant diseases
• Chromosomal mutation
• Aneuploidy and Poliploidy
• Detecting fetal mutation
 DNA-SEQUENCING
DECHIPERING THE CODE

SNP
Single Nucleotide Polymorphismus

A SNP is defined as a single base change in a

DNA sequence that occurs in a significant
proportion (more than 1 percent) of a large
population.
 SNP
• In human beings, 99.9 percent bases are same.
• Remaining 0.1 percent makes a person unique.
– Different attributes / characteristics / traits
• how a person looks,
• diseases he or she develops.

• These variations can be:

– Harmless (change in phenotype)
– Harmful (diabetes, cancer, heart disease, Huntington's
disease, and hemophilia )
– Latent (variations found in coding and regulatory regions,
are not harmful on their own, and the change in each gene
only becomes apparent under certain conditions e.g.
susceptibility to lung cancer)
 SNP
SNPs are found in
coding and (mostly) noncoding regions.

Occur with a very high frequency

about 1 in 1000 bases to 1 in 100 to 300 bases.

The abundance of SNPs and the ease with which they can be
measured make these genetic variations significant.

SNPs close to particular gene acts as a marker for that gene.

SNPs in coding regions may alter the protein structure made by

that coding region.
 SIGNIFICANCE OF SNPs

IN DISEASE DIAGNOSIS

IN FINDING PREDISPOSITION TO DISEASES

IN DRUG DISCOVERY & DEVELOPMENT

INVESTIGATION OF MIGRATION PATTERNS

 Dosage Compensation: Barr Body
• inactivated, condensed X chromosome
found in female cells.
• Barr bodies are essential to regulate
the amount of X-linked gene product
being transcribed. To ensure that X-
linked gene product doses are kept
similar between males and females,
one of the X chromosomes in a female
becomes very condensed.
Dosage Compensation: Barr Body

• X chromosome
Inactivation is random
and occurs at an early
point of development,
however, about 10% of
the genes on the
inactivated X
chromosome avoid
being silenced.
Dosage Compensation: Barr Body
The number of Barr bodies in a
cell is one less than the number
of X chromosomes. For
example:
• In a normal female with the
genotype 46XX , the number
of Barr bodies would be 1.
• In a normal male with the
genotype 46XY, the number
of Barr bodies would be 0.
Dosage Compensation: Barr Body
Incomplete dominance in human
hypercholesterolemia
GENOTYPES:
HH Hh hh
Homozygous Heterozygous Homozygous
for ability to make for inability to make
LDL receptors LDL receptors

PHENOTYPES:

LDL

LDL
receptor

Cell

Normal Mild disease Severe disease

 Genetic Counselor Activity
• Imagine that you are a Genetic
Counselor assigned to family to
discuss with them the possibility of
their child inheriting a genetic
disorder.

• You are given the family history and

whether or not the disorder is
Autosomal Dominant or Autosomal
Recessive.

• Draw Punnett Squares & Pedigree

to determine odds of children
inheriting the disease and answer
the questions on the worksheet.
 How to Construct a Pedigree
(Genogram)?
• A Pedigree is a visual showing the pattern of
inheritance for a trait. (Family tree)

• Symbols and Rules:

• Male = Female =
• Affected = Unaffected = Carrier =
• Link parents together with a line and then
make a vertical line to connect to offspring.
 Autosomal Dominant Pedigree
• Draw a Pedigree showing a cross between
Heterozygous parents that have 2 boys and 2
girls. (Show all possibilities)
Genotypes of Affected and Unaffected:
• AA and Aa = Affected aa = Unaffected
Aa Aa

aa Aa Aa AA
 Autosomal Recessive Pedigree
• Draw a Pedigree showing a cross between
Heterozygous parents that have 2 boys and 2
girls. (Show all possibilities)
Genotypes of Affected and Unaffected:
• AA=Unaffected Aa=Carrier, Unaffected
aa=Affected
Aa Aa

aa Aa Aa AA
 Sex-Linked Recessive Pedigree
• Draw a Pedigree showing a cross between a Red
eyed Male fruit fly and a Carrier Female fruit fly
which have 2 males and 2 females. (Show all
possibilities) Red is dominant to white.

• Genotypes of Parents:
• Male = XR Y Female = XR Xr

XRY XRXr

XRY XrY XRXR XRXr

 Examples of Autosomal Dominant Disorders
• Dwarfism
• Polydactyly and Syndactyly
• Hypertension
• Hereditary Edema

• Chronic Simple Glaucoma – Drainage system for fluid in the eye does not work and
pressure builds up, leading to damage of the optic nerve which can result in
blindness.
• Huntington’s Disease – Nervous system degeneration resulting in certain and early
death. Onset in middle age.
• Neurofibromatosis – Benign tumors in skin or deeper
• Familial Hypercholesterolemia – High blood cholesterol and propensity for heart
disease
• Progeria – Drastic premature aging, rare, die by age 13. Symptoms include limited
growth, alopecia, small face and jaw, wrinkled skin, atherosclerosis, and
cardiovascular problems but mental development not affected.
 Examples of Autosomal Recessive Disorders
• Congenital Deafness
• Diabetes Mellitus
• Sickle Cell anemia
• Albinism
• Phenylketoneuria (PKU) – Inability to break down
the amino acid phenylalanine. Requires
elimination of this amino acid from the diet or
results in serious mental retardation.

• Galactosemia – enlarged liver, kidney failure,

brain and eye damage because can’t digest milk
sugar
• Cystic Fibrosis – affects mucus and sweat glands,
thick mucus in lungs and digestive tract that
interferes with gas exchange, lethal.
• Tay Sachs Disease – Nervous system destruction
due to lack of enzyme needed to break down
lipids necessary for normal brain function. Early
onset and common in Ashkenazi Jews; results in
blindness, seizures, paralysis, and early death.
 What are Chromosomal Mutations?
• Damage to chromosomes due to physical or
chemical disturbances or errors during
meiosis.
• Two Types of Chromosome Mutations:
1. Chromosome Structure
2. Chromosome Number
 Problems with Chromosome Structure:

1. Deletion
2. Insertion
3. Inversion
4. Translocation
5. Duplication
 Problems with Chromosome Number:

ANEUPLOIDY
Abnormal number of some chromosome
In Somatic Cells:
• Trisomy 2n+1
• Monosomy 2n-1
• Tetrasomy 2n+2
In Gametes:
• Nullisomy n-1
• Disomy n+1
MONOSOMY AND TRISOMY CAUSED BY
NONDISJUNCTION
 Problems with Chromosome Number:

POLYPLOIDY : three or more complete

diploid = 2X N=X
triploid = 3X
tetraploid = 4X N = 2X
pentaploid = 5X
hexaploid = 6X N = 3X
duodecaploid = 12X N = 6X
 POLYPLOIDY
• Polyploidy is common in the plant kingdom.
• In the animal kingdom, natural occurrence of
polyploids is extremely rare.
• In general, polyploids are more nearly normal
in appearance than having monosomy or
trisomy, which is more disruptive to have one
extra chromosome in a pair.
 DEVELOPMENT OF
TRIPLOID AND TETRAPLOID ZYGOTE
 Human aneuploidy

• Humans, and animals in general, can’t tolerate

much chromosome aberration.
• In humans, aneuploids for X, Y, 13, 18 and 21
can survive to birth.
• Trisomy 13 = Patau syndrome
• Trisomy 18 = Edwards syndrome
• Trisomy 21 = Down syndrome
 Sex chromosome aneuploidy in
humans
Syndrome Name Sex Chromosomes Frequency
Turner XO 1/2500 f
Normal females XX
Triplo-X XXX, XXXX, XXXX 1/700 b
Nullo-X Y lethal
Normal males XY
Male XYY 1/1000 m
Klinefelter XXY, XXXY, XXXXY 1/500 m
Trisomy 21

Down
Syndrome
The chance of having a Down syndrome
child goes up with maternal age
Kleinfelter’s Syndrome
Karyotype XXY
 Fetal testing : Amniocentesis
• Karyotyping and biochemical tests of fetal cells
can help people make reproductive decisions
– Fetal cells can be obtained through amniocentesis

Amniotic
Centrifugation
Amniotic fluid
fluid withdrawn
Fluid

Fetus Fetal
(14-20 cells
Biochemical
weeks) tests

Placenta

Several
weeks later
Uterus Cervix Karyotyping
Figure 9.10A Cell culture
 Fetal Testing: Chorionic villus sampling is
another procedure that obtains fetal cells
for karyotyping

Fetus Several hours

(10-12 later
weeks)
Placenta
Suction Fetal cells Karyotyping
(from chorionic villi)

Some
Chorionic villi
biochemical
tests

Figure 9.10B
The End…