GENETIC DISORDERS

DR KETUT MULYADI SpPA(K)

FAKULTAS KEDOKTERAN UNIVERSITAS

UDAYANA 2010
 GENE AND HUMAN DISEASES
MUTATION

CLASSIFICATION
DISORDER RELATED TO
MUTATION IN SINGLE GENE WITH
LARGE EFFECT
CHROMOSOMAL DISORDER
COMPLEX MULTI GENIC
DISORDER
 HUMAN GENETIC
ARCHITECTURE
DNA
DNA SINGLE NUCLEOTIDE POLYMORFISM (SNP)
COPY NUMBER VARIATION (CNV)
RNA
RIBOSOMAL RNA (rRNA) 75%

STABLE RNA (tRNA, AND sn RNA ) 15%
mRNA (hnRNA) 10%
SMALL NON CODING (ncRNA) OR MICRO RNA
(miRNA)
 CATEGORIES OF HUMAN
MUTATION
SINGLE-BASE-PAIR-SUBSTITUTION
POINT MUTATION WITHIN CODING SEQUEN
MUTATION WITHIN NON CODING SEQUEN
DELETIONS
INSERTIONS
DUPLICATIONS
INVERSIONS
EXPANSION OF UNSTABLE REPEAT
SEQUENCES
TRINUCLIOTIDE REPEAT MUTATION
 SINGLE-BASE-PAIR-
SUBSTITUTION
TYPE OF NUCLEOTIDE
SUBSTITUTIONS
DNA POLYMERASE FIDELITY AND SINGLE-
NUCLEOTIDE SUBSTITUTIONS
SLIPPED MISPARING
HOTSPOTS FOR NUCLEOTIDE
SUBSTITUTIONS (CPG AND NON CPG
POINT MUTATIONS HOTSPOTS)
STRAND DIFFERENCE IN BASE
SUBSTITUTION RATES
 1.MENDELIAN DISORDERS
TRANSMISSION PATTERN OF SINGLE-GENE
DISORDERS
BIOCHEMICAL AND MOLECULAR BASIS OF SINGLE-
GENE (MENDELIAN) DISORDERS
DISORDERS ASSOCIATED WITH DEFECT IN
STRUCTURAL PROTEIN
DISORDERS ASSOCIATED WITH DEFECT IN
RECEPTOR PROTEIN
DISORDERS ASSOCIATED WITH DEFECT IN
ENZYME
DISORDERS ASSOCIATED WITH DEFECT IN
PROTEIN THAT REGULATE CELL GROWTH
1.1TRANSMISSION PATTERN OF
SINGLE-GENE DISORDERS
AUTOSOMAL DOMINANT DISORDERS
NERVOUS; HUNTINGTON DISEASES,
NEUROFIBROMATOSIS,MYOTONIC DYSTROPHY,
TUBEROUS SCLEROSIS

URINARY; POLYCYSTIC KIDNEY,

GASTROINTESTINAL; FAMILIAL POLYPOSIS COLI

HEMATOPOETIC; HEREDITARY SPHEROCYTOSIS,VON
WILLEBRAND DISEASES

SKELETAL; MARFAN SYNDROME, EHLERS-DANLOS
SYNDROME (SOME VARIANTS), OSTEOGENESIS
IMPERFECTA, ACHONDROPLASIA

METABOLIC; FAMILIAL HYPERCHOLESTEROLEMIA, ACUTE
INTERMITTENT PORPHYRIA
1.1TRANSMISSION PATTERN OF
SINGLE-GENE DISORDERS
AUTOSOMAL RECESSIVE DISORDERS

METABOLIC; CYSTIC FIBROSIS, PHENYLKETOURIA,
GALACTOSEMIA, HOMOCYTINURIA, LYSOSOMAL STORAGE
DISEASES, ALPHA1-ANTITRYPSIN DEFICIENCY, WILSON
DISEASES, HEMOCHROMATOSIS, GLYCOGEN STORAGE
DISEASES

HEMATOPOITIC: SICKLE CELL ANEMIA, THALASEMIA
ENDOCRINE: CONGENITAL ADRENAL HYPERPLASIA

SKELETAL: EHLERS-DANLOS SYNDROME (SOME
VARIANTS), ALKAPTONURIA
NERVOUS: NEUROGENIC MUSCULAR ATROPHIES,
FRIEDREICH ATAXIA, SPINAL MUSCULAR ATROPHY
1.1TRANSMISSION PATTERN OF
SINGLE-GENE DISORDERS
X-LINKED DISORDERS
MUSCULOSKELETAL: DUCHENE MUSCULAR
DYSTROPHY
BLOOD: HEMOPHILIA A AND B , CHRONIC
GRANULOMATOUS DISEASES, GLUCOSE-6-
PHOSPHATE DEHYDROGENASE DEFICIENCY
IMMUNE: AGAMMAGLOBULINEMIA, WISKOTT-
ALDRICH SYNDROME
METABOLIC: DIABETES INSIPIDUS, LESCH-
NYHAN SYNDROME
NERVOUS: FRAGILE-X SYNDROME
1.2 BIOCHEMICAL AND MOLECULAR BASIS OF
SINGLE-GENE (MENDELIAN) DISORDERS
ENZYME: PHENYLKETONURIA, TAY-SACH DISEASES, SEVERE
COMBINED IMUNODEFICIENCY
ENZYME INHIBITOR: EMPHYSEMA AND LIVER DISEASES
RECEPTOR: FAMILIAL HYPERCHOLESTEROLEMIA, VITAMIN D-
RESISTANT RIKECTS
TRANSPORT OXYGEN: ALPHA THALASEMIA, BETA
THALASEMIA, SICKLE CELL ANEMIA
TRANSPORT IONS: CYSTIC FIBROSIS
STRUCTURAL: EXTRACELLULAR : OSTEOGENESIS
IMPERFECTA, EHLERS-DANLOS SYNDROME, MARFAN
SYNDROME, CELL MEMBRANE: DUCHENE/BECKER
SPHEROCYTOSIS
HEMOSTASIS: HEMOPHILIA A
GROWTH REGULATION: HEREDITARY RETINOBLASTOMA,
NEUROFIBROMATOSIS TYPE 1
1.3 DISORDERS ASSOCIATED WITH DEFECT IN
STRUCTURAL PROTEIN

MARFAN SYNDROME: DISORDERS

CONECTIVE TISSUE BY CHANGES IN
SKELETON, EYES, AND
CARDIOVASCULER SYSTEM
EHLERS-DANLOS SYNDROME (EDS):
DEFECT IN SYNTHESIS OF FIBRILAR
COLAGEN
 EHLERS-DANLOS SYNDROME
(EDS)
EDS TYPE:
CLASSICAL(I/II): SKIN AND JOINT HYPERMOBILYITY,
ATROPHIC SCARS, EASY BRUISING

HYPERMOBILITY(III): JOINTS HYPERMOBILITY, PAIN,
DISLOCATIONS
VASCULAR (IV): THIN SKIN, ARTERIAL OR UTERINE
RUPTURE, BRUISING, SMALL JOINTS
HYPEREXTENSIBILITY
KYPHOSCOLIOSIS (VI): HYPOTONIA, JOINT
LAXITY,CONGENITAL SCOLIOSIS, OCULAR FRAGILITY

ARTHROCHALASIA(VIIa,b): SEVERE JOINT HYPERMOBILITY,
SKIN CHANGES (MILD), SCOLIOSIS, BRUISING
DERMATOSPARAXSIA(VIIc): SEVERE SKIN FRAGILITY,
CUTIS LAXA, BRUISING
 1.4 DISORDERS ASSOCIATED WITH
DEFECT IN RECEPTOR PROTEIN
FAMILIAR HYPERCHOLESTROLEMIA
 1.5 DISORDERS ASSOCIATED
WITH DEFECT IN ENZYME
LYSOSOMAL STORAGE DISEASES
SPHINGOLIPIDOSES: GM1 GANGLIOSIDOSIS, GM2
GANGLIOSIDOSIS

SULFATIDOSES: METACHROMATIC LEUKODYSTROPHY,
MULTIPLE SULFATASE DEFICIENCY, KRABBE DISEASES,
FABRY DISEASE, GAUCHER DISEASES, NIEMANN-PICK
DISEASE: TYPE A AND B

MUCOPOLYSACCHARIDOSES (MPSs): MPS I H (HURLER),
MPS II (HUNTER)
MUCOLIPIDOSES (MPSs): I-CELL DISEASES (ML II) AND
PSEUDO-HURLER POLYDYSTROPHY

OTHER DISESASES OF COMPLEX CARBOHYDRATES:
FUCOSIDOSIS, MANNOSIDOSIS,
ASPARTYGLYCOSAMINURIA

OTHER LYSOSOMAL STORAGE DISEASES: WOLMAN
DISEASES, ACID PHOSPHATE DEFICIENCY
1.6 DISORDERS ASSOCIATED WITH DEFECT IN
PROTEIN THAT REGULATE CELL GROWTH

DISORDERS TWO CLASSES OF GENE ;

PROTOONCOGENE AND TUMOR
SUPPRESOR GENE
TWO CLASSES OF GENE ARE
IMPORTANCE IN PATHOGENESIS OF
TUMOR BY MUTATION EFFECT
SOMATIC CELL
 2. COMPLEX MULTIGENIC
DISORDERS
1% OF POPULATIONS WITH
POLYMORPHISMS
EXP: IN TYPE 1 DIABETES FEW HLA-
ALLELE
IMMUNE MEDIATED INFLAMATORY
DISEASES,EXP: INFLAMTORY
MYOPATHIES
3. CHROMOSOMAL DISORDERS
NORMAL KARYOTYPE
STRUCTURAL ABNOMALITIES OF CHROMOSOMES
CYTOGENIC DISORDERS INVOLVING AUTOSOMES:
TRISOMY 21(DOWN SYNDROME), CHROMOSOMES
DELETION SYNDROME, TRISOMY 18 ( EDWARD
SYNDROME), TRISOMY 13 (PUTAU SYNDROME)
CYTOGENIC DISORDERS INVOLVING SEX
CHROMOSOMES:KLINEFELTER SNDROME, TURNER
SYNDROME, HERMAFRODIT AND
PSEUDOHERMAFRODIT
 4. SINGLE-GENE DISORDERS WITH
NONCLASSIC INHERITANCE
DISEASES CAUSED BY
TRINUCLEOTIDE-REPEAT MUTATIONS
MUTATIONS IN MITHOCONDRIAL
GENES-LEBER HEREDITARY OPTIC
NEUROPATHY
GENOMIC IMPRINTING
GONADAL MOCAICISM
 MOLECULAR DIAGNOSIS OF
GENETIC DISEASES
INDICATION FOR ANALYSIS OF GERM LINE
GENETIC ALTERATIONS
INDICATIONS FOR ANALYSIS OF ACQUIRED
GENETIC ALTERATION
PCR AND DETECTION OF DNA SEQUENCE
ALTERATIONS
POLYMORPHIC MARKERS AND MOLECULAR
DIAGNOSIS
MOLECULAR ANALYSIS OF GENOMIC ALTERATIONS
EPIGENETIC ALTERATION
RNA ANALYSIS