PATTERN OF

INHERITNCE
POLA PENURUNAN
SIFAT
Kiagus muhammad arsyad
Bagian biologi kedokteran
Fakultas kedokteran UNSRI

LEARNING OBJECTIVES

1.
2.
3.

After finished this lecture, student be able

to know and understand regarding to :
The patterns of inheritance,
Mendelian and Non Mendelian inheritnce,
The diseases inherited by two pattern of
inheritance

LEARNING CONTENTS
Introduction
Mendelian inheritance
Non mendelian inheritance

INTRODUCTION
Genetics

=
the branch of Biology which is concerned
with heredity and individual variation and
characteristics

George Mendel,
Mendels law
Others

THE TYPES OF
INHERITANCE
1.

Mendelian inheritance

2.

Non-Mendelian inheritance

MENDELIAN INHERITANCE
MENDELIAN INHERITANCE
1.
2.
3.
4.

Autosomal dominant
Autosomal recessive
X-linked dominant
X-linked recessive

Autosomal dominant (AD)

SHT DASAR2 GENETIKA PENYAKIT

Contoh autosomal
dominant inheritance
1.
2.
3.
4.

Hereditary Breast cancer

Myotonic dystrophy
Hereditary colon cancer
Tongue curling

SHT DASAR2 GENETIKA PENYAKIT

2. AUTOSOMAL RECESSIVE
(AR)
Kelainan AR baru muncul jika ada 2
copy gene yang bermutasi.
Penderita biasanya mempunyai ortu
yang sehat, tapi masing masing
adalah carier.
2 orang yang carier maka peluang
mempunyai anak dengan AR adalah
25%.

SHT DASAR2 GENETIKA PENYAKIT

Autosomal recessive

SHT DASAR2 GENETIKA PENYAKIT

3. X-LINKED DOMINANT
Kelainan X-linked dominant disebabkan
adanya mutasi gen di X
chromosome.
Hanya sedikit kelainan yang termasuk
kelompok ini
Anak laki2 lebih sering menderita
dibandingan anak perempuan
Peluang menurunkan kelainan X-linked
dominant ini berbeda antara laki2 dan
perempuan.

SHT DASAR2 GENETIKA PENYAKIT

3. X-LINKED DOMINANT

Anak laki2 dari ayah dengan kelainan X-linked

dominant tidak menderita tetapi anak
perempuannya akan mewarisi ini semua (Carier).
Perempuan dengan kelainan X-linked
mempunyai peluang 50% memiliki puteri atau
putera yang menderita kelainan ini pada setiap
kehamilan.
Beberapa kondisi X-linked, misalnya
Aicardi Syndrome, fatal untuk anak laki2,
karena itu hanya anak perempuan yang ada
penyakit itu atau
anak laki laki dengan Klinefelter Syndrome
ada
2 X khromosom).
SHT DASAR2 GENETIKA PENYAKIT

.4. X-LINKED RECESSIVE

Kelainan X-linked recessive adalah juga

disebabkan oleh mutasi pada X chromosome.
Lelaki lebih sering menderita dibandingkan
perempuan, dan peluang menurunkannya
berbeda antara laki2 dan perempuan.
Anak laki2 dari ayah dengan kelainan X-linked
recessive tidak akan menderita penyakit ini, anak
perempuannya akan menjadi Carier.
Perempuan carier X-linked recessive mempunyai
peluang 50% memiliki anak laki2 yang menderita
dan 50% peluang mempunyai anak perempuan
yang Carier.
SHT DASAR2 GENETIKA PENYAKIT

X-linked

X Y

X X

X Y X Y X X

X X

TUGAS :
CARI PENYAKIT PENYAKIT DENGAN X LINKED DOMINAT DAN Y LINKED

SHT DASAR2 GENETIKA PENYAKIT

X-LINKED INHERITANCE
Some important examples
Duchenne muscular dystrophy (DMD)
Haemophilia (A and B)
Fragile X mental retardation
X-linked immune deficiencies
Colour blindness

SHT DASAR2 GENETIKA PENYAKIT

SHT DASAR2 GENETIKA PENYAKIT

Summary of Extensions to Mendels Analysis

Rules
As Mendel Showed

Extension

Effect on
Heterozygous
Phenotype

Complete
Dominance

Incomplete Dominance
Codominance

Unlike either
homozygote

Two Alleles

Multiple Alleles

Multiple
phenotypes

All Alleles Viable

Recessive Lethal Alleles

No Effect

One Gene One

Trait

Pleiotropy: one gene

several traits

Several traits
affected
differently

NON-MENDELIAN INHERITANCE
Reduced penetrance
Anticipation
Genomic imprinting
Mitochondrial inheritance
Multifactorial and polygenic inheritance

NON-MENDELIAN INHERITANCE
Reduced penetrance
Anticipation
Genomic imprinting
Mitochondrial inheritance
Multifactorial and polygenic inheritance

REDUCED PENETRANCE
+

Not all persons with a mutation will develop the

disease
Examples: Hereditary cancer, Spastic paraplegia

NON-MENDELIAN INHERITANCE
Reduced penetrance
Anticipation
Genomic imprinting
Mitochondrial inheritance
Multifactorial and polygenic inheritance

ANTICIPATION
Not all
generations
are affected
Always
inherited from
the mother
Girls are less
severely
affected than
the boys

Anticipation
The severity of the disease increases and the age of onset
decreases in subsequent generations

The underlying mutation

with every generation

Examples:

is a triplet repeat that expands

Genomic imprinting

Disease only if inherited from the mother

Girls and boys are equally affected

Imprinting
Parent of origin effect
Only one of the paternal chromosomes is active, the other is
inactivated by imprinting

Examples:
Angelman syndrome
Prader-Willi syndrome
Beckwitt-Wiedemann syndrome

15q11-q13
No paternal contribution:
Prader-Willi syndrome
No maternal contribution:
Angelman syndrome

Prader-Willi syndrome
70%
Paternal deletion
Maternal uniparental disomy
Imprinting centre mutations

30%
<2%

Angelman syndrome

Maternal deletion

70%

Paternal uniparental disomy

Imprinting centre mutations
5%
UBE3A mutations
15%
Unknown

5%
5%

Downloaded from: StudentConsult (on 2 December 2009 08:20 AM)

2005 Elsevier

Angelman syndrome pedigree

+: c.1018_1020del mutation in the UBE3A gene

Always inherited from the mother, girls and boys are equally affected

(Micro)deletion 15q11-q13

Deletion: Prader-Willi syndrome

Downloaded from: StudentConsult (on 2 December 2009 08:20 AM)

2005 Elsevier

(Micro)deletion 15q11-q13

Deletion: Angelman syndrome

Downloaded from: StudentConsult (on 2 December 2009 08:20 AM)

2005 Elsevier

UPD15
Angelman syndrome

Downloaded from: StudentConsult (on 2 December 2009 08:20 AM)

2005 Elsevier

UPD15:
Prader-Willi syndrome

Downloaded from: StudentConsult (on 2 December 2009 08:20 AM)

2005 Elsevier

Imprinting centre mutation

Prader-Willi syndrome

Downloaded from: StudentConsult (on 2 December 2009 08:20 AM)

2005 Elsevier

Downloaded from: StudentConsult (on 2 December 2009 08:20 AM)

2005 Elsevier

Imprinting centre mutation

Angelman syndrome
Downloaded from: StudentConsult (on 2 December 2009 08:20 AM)
2005 Elsevier

UBE3A mutation

Angelman syndrome
Downloaded from: StudentConsult (on 2 December 2009 08:20 AM)
2005 Elsevier

Methylation testing for Prader-Willi/Angelman

Test in blood for active and inactive
copy of SNURF/SNRPN

Brain specific

Downloaded from: StudentConsult (on 2 December 2009 08:20 AM)

2005 Elsevier

Southern blot analysis

P

P A

P
KB17

Mitochondrial diseases

Due to mutations in nuclear DNA

Autosomal recessive inheritance
Mendelian
Due to mutations in mitochondrial DNA
Mitochondrial (maternal) inheritance
Non-mendelian

Mitochondrial inheritance pattern

10
%

75
%

15% 60
%

7%

85
%

15
%

5%

10
90
%
%

m.3243A>G mutation in mitochondrial DNA

Encephalopathy, lactic acidosis, stroke-like episodes
Diabetes mellitus

16569
basepairs

Mitochondria:
ATP production

13 protein coding genes

22 tRNA genes
2 rRNA genes

Mitochondrial inheritance
Heteroplasmy: The percentage of the mutated DNA determines the
severity of the disease

The tissue specific distribution can influence the clinical picture

Examples:
LHON

Leber Hereditary Optic Neuropathy

MELAS Mitochondrial Myopathy, Encephalopathy, Lactic

Acidosis, and Stroke-like episodes
MERRF

Myoclonic Epilepsy associated with Ragged-Red Fibers

Homoplasmy/Heteroplasmy

Downloaded from: StudentConsult (on 28 December 2009 04:12 PM)

2005 Elsevier

Non-Mendelian inheritance
Reduced penetrance
Anticipation
Genomic imprinting
Mitochondrial inheritance
Multifactorial

and polygenic inheritance

Multifactorial disease

Multifactorial inheritance
No clear pattern of inheritance
Common diseases
Examples: Diabetes mellitus
Spina bifida
Cleft/lip palate
Autism / Bipolar disorders / Schizophrenia
Dementia

Burden of genetic disease in humans

Type of genetic disease

Prevalence (%)
Monogenic
1
Chromosomal aberrations
0.5
Multifactorial, congenital / juvenile onset
4
Multifactorial, adult onset
60

Non-mendelian inheritance
Polygenic disease
Simultaneous presence of mutations in
different genes result in the phenotype
Mutation in gene A and B and C -> disease
Multifactorial disease
Combination of genetic heterogeneity and polygenic inheritance
and the effect of adverse environmental influences
Mutations in (A AND B AND C) +

disease

Non-mendelian inheritance
Reduced penetrance
Not all carriers of a mutation develop the disease
Anticipation
The severity of the disease increases and the age of onset
decreases in subsequent generations
The underlying mutation is a triplet repeat that expands
with every generation
Genomic imprinting
Parent of origin effect
Only one of the paternal chromosomes is active, the other is
inactivated by imprinting

Non-mendelian inheritance
Mitochondrial inheritance
Heteroplasmy: The percentage of the mutated DNA determines
the severity of the disease
The tissue specific distribution can influence the clinical picture
Polygenic inheritance
Simultaneous presence of mutations in different genes
result in the phenotype

Multifactorial inheritance
Combination of genetic heterogeneity and polygenic
inheritance and the effect of adverse environmental
influences

Daftar Rujukan :
1.
2.

3.

4.

54

DP Snustad, MJ Simmons : Principle of Genetics,

3 rd edition, John Wiley & Sons, New York, 2003.
R.B. Mueller, ID Young.: Emerys Elements of
Medical Genetic, 10th Edition, Edinburgh-London,
1998.
Glen and Susan Toole : New Understanding
Biology For advanced Level, 4th edition, Stanley
Thornes Pubs, Ltd, 1999.
Thomson and Thomson Genetic in Medicine,
2004

KMA MUTASI KHROMOSOM

GENE