GENETICS: DEFINE US

(Dasar-Dasar Genetika)

dr. Rahma Triliana, S.Ked. M.KesPathophysiology Of Genetic Diseases Block

Medical FacultyMalang Islamic University (UNISMA)

2007

- Physical And Functional Unit of Heredity- Carries Information From One Generation to the Next. - Necessary for Production of Functional Protein or RNA - The Entire DNA Sequence Including Exons, Introns and Non

Coding Transcription-control Regions

GENE

GENETICSScience that study - Gene- Genome/Genomic- Genetic Control, Expression, Code, Markers, etc.- Gene-related disease

Overall Process Which the Information Encoded in Gene Is Converted Into an Observable Phenotype (Protein)

GENE EXPRESSION

Total Genetic Information Carried by a Cell or OrganismGENOME

Comparative Analyses of the Complete Genomic Sequences from Different Organisms; Used to assess evolutionary relations among species and to predict the number & general types of proteins produced by an organism

GENOMICS

All of the Mechanism in Transcription (Most Common), Processing, Stabilization And Translation That Involved in/ Controlled Gene Expression

GENE CONTROL

Alleles Associated With an Easily Detectable Phenotypes That Are Used Experimentally to Identify or Select for a Linked Gene, a Chromosome, a Cell, or an Individuals. Non Coding DNA-sequences That Are Vary Among Individuals (DNA-polymorphysms) Can Serve As a Genetic Markers

GENETIC MARKERS

Set of Genes That Arose by Duplication of a Common Ancestral Gene and Subsequent Divergence Due to Small Changes in the Nucleotide Sequence

GENE FAMILY

TERMINOLOGY

• Consist Of Repeating Nucleotide Units

• Nucleic Acids Strands

• Form A Linear Polymer With End-to-end Directionality

• DNA Carries Information In GENETIC Code

• Genetic Code Set Of Rules Whereby Nucleotide Triplets (3 Base Pairs = Codons) In DNA Or RNA That Specify Amino Acids In Proteins

GENE STRUCTURE GENE STRUCTURE Nucleotide- A Phosphate Ester- A Pentose Sugar- A Heterocyclic Base Purines

& Pyrimidines

NUCLEIC ACIDS STRANDS NUCLEIC ACIDS STRANDS

- a Double Helix with Complementary Anti-parallel Strands Watson-Crick base pairing

- Can Undergo Reversible Strand Separation

- Utilize 2-deoxy-d-ribose

RNA Single Double DNA

- Different Types Exhibit Various Conformations Related to Their Functions

- mRNA, tRNA, rRNA, snRNA

- Utilize d-ribose

Transcription

DNA Are Packed In CHROMOSOME During CELL DIVISION

4 BASIC GENETIC PROCESS

TRANSCRIPTIONa Process of Protein-coding Genes & Formation Of Functional mRNA

Carry genetic code for a certain/several protein

1. A Template DNA Transcribed into a Complementary RNA by RNA Polymerase form Precursor mRNAs

2. mRNA can undergo post-transcriptional editing to Form a Functional mRNAs &/ degraded

3. Alternative RNA Splicing Can Increases the Number of Proteins Expressed from a Single Eukaryotic Gene

• Messenger RNA (mRNA) Carries Information• Folded Structure of Transfer RNA (tRNA) Promotes Decoding

Functions• Aminoacyl-tRNA Synthetases Activate Amino Acids by

Covalently Linking Them to tRNAs • Ribosomes Are Protein-Synthesizing Machines• Methionyl-tRNAi

Met Recognizes the AUG Start Codon • Translation Initiation Usually Occurs Near the First AUG Closest

to the 5’ End of an mRNA • During Chain Elongation Each Incoming Aminoacyl-tRNA

Moves Through Three Ribosomal Sites• Translation Is Terminated by Release Factors When a Stop

Codon Is Reached• Polysomes and Rapid Ribosome Recycling Increase the

Efficiency of Translation

TRANSLATION

TRANSLATION

PROTEIN PROCESS & PACKAGE

• Require a Primer to Initiate

• Duplex DNA Is Unwound, Daughter Strands Are Formed at DNA Replication Fork

• Helicase, Primase, DNA Polymerases, and Other Proteins also Participate

• Generally Occurs Bidirectionally from Each Origin

DNA REPLICATION

CONTROL

OF

G ENE

GENETIC DISEASE1. Disease Caused by Gene Defect That Effect Cells &/

Organ Function2. Gene Defect Abnormalities in Genetic Sequence

That Effect 1 / > Basic Genetic Process &/ Protein Production

3. Can Be Traced Down in Family Pedigree & Mendelian

Due to-Gene Mutation-Chromosomes Abnormality -Defect in Mitosis &/or Meiosis Process

Chromosomal Disorder More / Less Set of Chromosome a. Euploidy Whole Set Defect (Mono, Di, Poly)- Ploidb. Uneuploidy Uneven Set Defect (Mono, Di, Nulli, Poly)-somyE.G. Turner Syndrome (45 X), Down Syndrome (47, + 21), Trisomy 13,

(47, + 13) & Trisomy 18 (47, +18), Klinefelter Syndrome (47 XXY, 48 XXXY), Triple X (47, XXX), Presence of Philadelphia Chromosome (Leukemia)

Structure Defecta. Deletion (Cri-du-cat Syndrome (46,XX/XY, 5p-)b. Duplicationc. Inversiond. Ring Chromosome

CLASSES of GENETIC DISEASE

Monogenic Disease Single Gene Defect• Autosomal Dominant (E.G. Mutation in Ldl-r-gene

Familial Hypercholesterolemia, Huntington Disease)• Autosomal Recessive (Mutation of Glu – Val at B6

Position of Globin Sickle Cell Anemia, Mutation of Phe Hydroxylase Gene Phenylketonuria)

• Sex-linked (Duchenne Muscular Dystrophy Gene Defect in Dystrophin Synthesis, Hemophilia A Gene Defect in Factor VIII Synthesis)

• Mitochondrial DNA Defect Effect Oxidation-phosphorylation-process

CLASSES of GENETIC DISEASE

Multifactorial • Disease Caused by Combination of Gene &

Environmental Factors• Gene Effect Susceptibility &/ Hastened/

Escalate DiseaseE.G. - Ischemic Heart Disease- Essential Hypertension- Arteriosclerosis

CLASSES of GENETIC DISEASE