Sie sind auf Seite 1von 65

GENETIKA MANUSIA

4/15/2014

Cells are divided into two main classes

4/15/2014

Yeasts

Even in its simplicity, the yeast cell exhibits the typical features of eukaryotic cells It contains a distinct nucleus surrounded by a nuclear membrane, its genomic DNA is organized as 16 linear chromosomes, and its cytoplasm contains a cytoskeleton and subcellular organelles. Yeasts can be readily grown in the laboratory. Although yeasts do not replicate as rapidly as bacteria, they still divide as frequently as every 2 hours and can easily be grown as colonies from a single cell.
4/15/2014 3

The major features of eucaryotic cells. The drawing depicts a typical animal cell, but almost all the same components are found in plants and fungi and in single-celled eucaryotes such as yeasts and protozoa. Plant cells contain chloroplasts in addition to the components shown here, and their plasma membrane is surrounded by a tough external wall formed of cellulose.
4/15/2014 4

4/15/2014

Genetika Manusia
Mempelajari peran gen dalam proses-proses dasar kehidupan manusia Mempelajari keanekaragaman dan pola pewarisan sifat manusia, bersama-sama dengan biologi molekular, biokimia dan biologi sel Sangat berkaitan dengan genetika medik yang mempelajari diagnosis, pengobatan dan penanganan penyakit herediter Lebih kompleks dari yang digambarkan oleh Mendel

4/15/2014 6

Genome
Keseluruhan gen atau DNA yang terdapat
dalam sel manusia : nuclear dan mitochondrial genome Gen : DNA polinukleotida

4/15/2014

Human Genome Project : penentuan sekuens genome manusia secara lengkap sehingga dapat menyediakan data dasar untuk pemahaman penyakit, pengembangan alat diagnostik, pencegahan dan terapi. Sekuens genome yang lengkap akan dapat mengidentifikasi semua gen pada manusia variasi gen pada kondisi sehat dan sakit

4/15/2014

Table 4-1 Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

What is DNA?

Thymine (T) Cytosine (C)

Adenine (A) Guanine (G)

Over 3 billion base pairs, 30,000 genes Humans are over 99.9% identical
4/15/2014 10

Nuclear DNA Structure

proposed by Watson dan Crick Each linear molecule consists of 2 strand joined by hydrogen bond between purine and pyrimidine bases adenine join with thymine, involve the formation of 2 hydrogen bonds guanine join with cytosine, involve the formation of 3 hydrogen bonds The 2 DNA strands are complementer, adenine = thymin and guanine = cytosine 4/15/2014

11

Watson and Crick

Double helix Bases in the inside Sugar-phosphat backbone on the outside Two strands run in opposite direction Bases are paired by hidrogen bonds (A-T, G-C)

Figure 4-3 Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

12

Figure 4-4 Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

13

4/15/2014 Figure 1-2 Molecular Biology of the Cell, Fifth Edition ( Garland Science 2008)

14

Figure 4-5 Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

15

NUCLEIC ACID
Nucleic acid is a macromolecule consists of nucleotides (polynucleotides)
Purines and pyrimidines are nitrogen-containing heterocycles, cyclic compounds whose rings contain both carbon and other elements (hetero atoms). Adenine and guanine are purine; thymine, uracyl and cytosine are pyrimidine Nucleosides are derivatives of purines and pyrimidines that have a sugar linked to a ring nitrogen. The sugar is linked via a beta-N-glycosidic bond, to N-1 of a pyrimidine or to N-9 of a purine Mononucleotides are nucleosides with a phosphoryl group esterified to a hydroxyl group of the sugar.
4/15/2014 16

Purine, Pyrimidine and Nucleosides

4/15/2014

17

Nucleotides

Numerals with a prime (eg, 2 or 3) indicate the sugar, numerals without a prime indicate the base. The prefix d (deoxy) indicates that the sugar is 2-deoxyD-ribose, without prefix d indicates that the sugar is Dribose.
4/15/2014 18

The Nomenclature of Base, Nucleoside and Nucleotide

4/15/2014

19

NUCLEIC ACID
There are two nucleic acids based on ribose: DNA is deoxyribose; RNA ribose DNA is the chemical basis of heredity, organized into genes, the fundamental units of genetic information DNA contains 4 deoxynucleotides : deoxy adenilate, guanilate, cytidylate and thymidylate RNA contains uracil instead of thymine Basic information pathway : DNA to RNA to protein is the central dogma of molecular biology
4/15/2014 20

DNA
Genetic materials, in eucaryotes DNA present in the nucleus, in procaryotes DNA is dispersed in the cytoplasma (recently known as nucleoid) In human, DNA also exists in the mitochondria (mitochondrial DNA = mtDNA) DNA bound to nucleoprotein (histone) to form nucleosome. Together with nonhistone proteins and RNA form chromatin (eu- dan heterochromatin).
Nonhistone proteins include enzymes important for DNA replication and translation.
4/15/2014 21

One purpose of the molecules that comprise chromatin, particularly the histones, is to condense the DNA.
Genome : all DNA contain in the cell. Human have 3 billion base pairs of nuclear genome and 16,500 base pairs of mitochondrial genome.

Chromatin demonstrated dense spherical particles called nucleosomes, which are approximately 10 nm in diameter and connected by DNA filaments Core histone : H2A, H2B, H3 and H4 make histone octamer, bound tightly. H1 histone least tightly bound to the core histone.
4/15/2014 22

4/15/2014

23

4/15/2014

24

Bases are linked with deoxyribose by mean of Nglicosidic linkage, purine and pyrimidine bases are held together by phosphodiester backbone between 2 deoxyribosil moeities The 2 strands are antipararel, one strand runs in the 5 3, the other runs in the 3 5
The 2 strands, which bases held together by hydrogen bond, wind around central axis to form a double helix right handed One strand act as a template strand, the opposite is considered as coding strand
4/15/2014 25

Double helix DNA

major groove

minor groove

4/15/2014

26

DNA (genes) are organized into coding region (exon) which will be translated into proteins and noncoding region (intron/intervening sequence = IVS) which will not be translated into protein.

During mRNA maturation, noncoding region will be removed by a process called splicing. In human, 30,000 genes have been characterized; however, scientists believe that the number of genes should be at least 80,000.
All genes only comprises 3% of human genomes, others are introns and extragenic DNA

4/15/2014

27

Exon and Intron in Genes

4/15/2014

28

RNA
Transcribed from DNA, different structure

Involve in protein synthesis (mRNA : template for prot synt, tRNA : adapter molecule for transcription, rRNA : formation of ribosome) Involve in replication (oligonucleotides) dan RNA processing (snRNA, snRNP atau snurp, hnRNA : mRNA precursor)
Act as an enzyme (ribozyme: peptidyl transferase)
4/15/2014 29

DNA vs RNA DNA


deoxyribose thymine double-strand guanine = cytosine, adenine = thymine Denaturation to single strand

RNA
ribose uracyl single-strand Not equal
Hydrolisis by alkali to mononucleotides

4/15/2014

30

4/15/2014

31

RNAs
1. Messenger RNAs (mRNAs):

are the genetic coding templates used by the translational


machinery to determine the order of amino acids incorporated into an elongating polypeptide in the process of translation.

2. Transfer RNAs (tRNAs): small RNAs form covalent attachments to individual amino acids and recognize the encoded sequences of the mRNAs to allow correct insertion of amino acids into the elongating polypeptide chain. 3. Ribosomal RNAs (rRNAs): are assembled, together with numerous ribosomal proteins, to form the ribosomes. Ribosomes engage the mRNAs and form a catalytic domain into which the tRNAs enter with their attached amino acids. The proteins of the ribosomes catalyze all of the functions of polypeptide synthesis.

4/15/2014

32

1. mRNA Convey information in a gene to proteinsynthesizing machinery Synthesized in nucleus, translated in cytoplasm

4/15/2014

33

2. tRNA

Adapter for the translation of mRNA. There are 20 species of tRNA corresponding to each of the 20 amino acids The primary structure allow folding and intrastrand complementarity, so 4/15/2014 appear like a

34

Figure 6-52 Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

35

3. rRNA Ribosome : nucleoprotein structure (rRNA and protein) act as the machinery for the protein synthesis Mammalian ribosome contains 2 major nucleoprotein, a large one of 60S (5S, 5,8S, 28S rRNA and 50 polypeptide) and a small one of 40S (18S rRNA and 30 polypeptide)

4/15/2014

36

Ribosome 40S

Ribosome 80S

4/15/2014

37

All Cells Replicate Their Hereditary Information by Templated Polymerization

The duplication of genetic information by DNA replication. In this process, the two strands of a DNA double helix are pulled apart, and each serves as a template for synthesis of a new complementary strand.
4/15/2014 38

DNA replication

Each parental strands serves as a template

Central enzyme : DNA polymerase


Catalyze joining of deoxyribonuclease 5 triphosphat (dNTP)

4/15/2014

39

DNA sequence is a kind of language

The nucleotide sequence of the human -globin gene

4/15/2014

40

All Cells Transcribe Portions of Their Hereditary Information into the Same Intermediary Form (RNA)

4/15/2014

41

Genetic code

4/15/2014

42

DNA sequence is a kind of language


OLD MAN SIT AND EAT TWO PIE AAG CTC GCT GGA TTG GAT ATA UUC GAG CGA CCU AAC CUA UAU Phe Glu Arg Pro Asn Leu Tyr * LDM ANS ITA NDE ATT WOP IE * AGC TCG CTG GAT TGG ATA TA * UCG AGC GAC CUA ACC UAU AU DNA RNA DNA RNA Protein

Ser

Ser Asp Leu Thr Tyr

Protein

ROL DMA NSI TAN DEA TTW OPI E TAA GCT CGC TGG ATT GGA TAT A DNA

AUU CGA GCG ACC UAA CCU AUA U


Ile Arg Arg Thr STOP

RNA
Protein

The nucleotide sequence of the human -globin gene


4/15/2014 43

Transcription
Eukaryotic transcription is more complex than prokaryotic transcription and, it has seemed that every eukaryotic gene was unique requiring its own transcription machinery. The promoters for different genes are different. Each contains a combination of sites to which specific protein factors bind. All of these factors help RNA polymerase to bind in the correct place and to initiate transcription. The repertoire of transcription factors and transcription factor binding sites is not unlimited

4/15/2014 44

Transcription
First and highly regulated in gene expression is a beginning of series of events to produce functional RNA Newly synthesized RNA modified in various ways converted to its functional form

Exception !!
Bacterial mRNAs used immediately as template while still being transcribe

4/15/2014

45

Figure 6-21 Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

46

Figure 6-7 Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

47

Figure 6-8a Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

48

Processing of mRNAs

In eukaryotic:
Initial products of transcripiton (premRNAs) extensively modified before export from the nucleus

A. Modification of both ends of the molecule B. Removal of introns from its middle

4/15/2014

49

Modification of 5 end

Addition of a cap structure (7methylguanosine)

Align mRNAs on the ribosome during translation

50

4/15/2014

Figure 6-22b Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

51

Modification of 3 end

Cleavage the primary transcription up to 20 bp

Addition of poly A-tail (approx. 200 bp) polyadenylation

52

4/15/2014

Figure 6-37 Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

53

Removal of introns by splicing

Coding sequence (exon) interrupted by non coding sequence (intron) Most genes contain multiple introns 10x more than the exons
54 4/15/2014

4/15/2014

55

Processing of ribosomal RNA (rRNA)

Figure 6-42 Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

56

//

4/15/2014

57

4/15/2014

58

Figure 6-72 Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

59

Figure 6-74 Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

60

All Cells Translate RNA into Protein in the Same Way

4/15/2014

61

Figure 6-84 Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

62

Figure 6-73 Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

63

Figure 6-97 Molecular Biology of the Cell ( Garland Science 2008)

4/15/2014

64

4/15/2014

65