GENETICS an Introduction

GENETICS an Introduction GENETICS an Introduction

• The Aim of these session is to provide the student with a sound understanding of normal and disease processes at the genetic level.

• These sessions will be comprised of two different modalities of expressions such as SEMINARS & LECTURES.

• Each session will cover the general features of the normal and disease condition(s), and will focus on current understanding of the biochemical effects of normal conditions as well as biochemical defects (metabolic, structural or genetic) which underlie the disease state.

By the end of these sessions, the students should be able to

demonstrate the ability to discuss the normal and genetic

mechanisms that underlie several normal and disease processes.

By the end of these sessions, the students should be able to

demonstrate the ability to discuss the normal and genetic

mechanisms that underlie several normal and disease processes.

Aim of These Sessions

Chemistry, classification and characteristics of Purine and

Pyrimidine Bases

Chemistry, classification and characteristics of Nucleosides

and Nucleotides.

Classification, Function and occurrence of nucleotides in

human tissue and role of Nucleotides in the Human Body.

Role of Cyclic AMP and Cyclic GMP in the body.

Protein Synthesis

Lectures

Chromosome structure, classification and abnormalities

Genetic Variation and mutations

Genetic patterns of inheritance

Inborn errors of metabolism

Cancer genetics,

Gene therapy,

Genetic counseling, and ethical issues and decision making in

medical genetics.

Genetic screening

Chromosome structure, classification and abnormalities

Genetic Variation and mutations

Genetic patterns of inheritance

Inborn errors of metabolism

Cancer genetics,

Gene therapy,

Genetic counseling, and ethical issues and decision making in

medical genetics.

Genetic screening

• Human body is made up of 75 trillion cells

• Every cells has a nucleus

• In the nucleus they contain Genes

• 99.9 % of genes are present in nucleus

• Few genes are present in Mitochondria

• Genes are small part of DNA

• DNA - is a nucleic acid that contains the genetic instructions specifying

the biological development of all cellular forms of life

• DNA is made up of Nucleotides

• Nucleotides is comprised of Sugar, Nitrogenous base and phosphate

Genetic Information• Gene – basic unit of genetic information. Genes determine the

inherited characters.

• Genome – the collection of genetic information.

• Chromosomes – storage units of genes.

• Human has 23 pairs of chromosomes

• These 46 chromosomes contain 6 billions individual characters of the genetic code.

• Gene – basic unit of genetic information. Genes determine the inherited characters.

• Genome – the collection of genetic information.

• Chromosomes – storage units of genes.

• Human has 23 pairs of chromosomes

• These 46 chromosomes contain 6 billions individual characters of the genetic code.

Human GenomeHuman diploid cells contain 46 chromosomes arranged in 23 pairs

• 2 sex chromosomes (X,Y):XY – in males.XX – in females.

• 22 pairs of chromosomes named autosomes.

Chimpanzee contain 24 pairs of chromosomes Cow contain 30 pairs of chromosomes Chicken contain 39 pairs of chromosomes Bnana contain 11 pairs of chromosomes

Chimpanzee contain 24 pairs of chromosomes Cow contain 30 pairs of chromosomes Chicken contain 39 pairs of chromosomes Bnana contain 11 pairs of chromosomes

Who determines the male or female Gender

• Is the mother

• Is the father

• Or is it by chance from any of the two

50% Girls50% Boys

50% Girls50% Boys

Genotypes Phenotypes• At each locus (location of a gene/marker on the

chromosome) there are 2 genes. These constitute the individual’s genotype at the locus.

• The expression of a genotype is termed a phenotype. For example, hair color, weight, or the presence or absence of a disease.

Genetics Review Genetics ReviewT A C G C T T C C G G A T T C A

A

Transcription

Transcription

A U G C G A A G G C C U A A G U U A U G C G A A G G C C U A A G U U

DNA

RNARNA

TranslationTranslation

ABCDE

ProteinAmino AcidsAmino Acids

Protein Synthesis

Translation of the Genetic Code

Proteins/ Gene Expression

• Proteins make up all living materials

• Proteins are composed of amino acids – there are 20 different amino acids

• Different proteins are made by combining these 20 amino acids in different combinations

• Proteins are manufactured in the ribosomes under the strict control and order of DNA.

• The DNA language is made up of letters which are ATGCATATGGAATCAG

• These letters forms Words• ATC GCA GGA AUU AUG

• These words make sentences

•

Protein Synthesis

DNA and Protein Synthesis

• DNA contains the genetic information to make amino acids•Amino acids combine to make proteins

• These proteins determine the physical traits of an organism and control cellular functions.

• Proteins do everything, and DNA gets all the credit!

• Transcription is the Reading of the DNA and

Changing the code to mRNA.• Translation is changing the mRNA into a trait by

Using tRNA to interpret the mRNA.

Transcription & Translation

• DNA has regions of coding and non-coding. The regions of DNA that code for proteins or traits are called EXONS, while the regions that do not code for proteins are called INTRONS.

Introns & Exons

Making a Protein—Transcription•First Step: Copying of genetic information from DNA to RNA called Transcription

•Part of DNA temporarily unzips and is used as a template to assemble complementary nucleotides into messenger RNA (mRNA).

• Transcription occurs inside the nucleus in a two step sequence of events.– Pre-mRNA includes both introns and exons for the

gene.– mRNA is only the coding portion (exons).

• Translation occurs in the cytoplasm at the ribosomes.– Reminder: The are three (3) types of RNA

• Messenager (mRNA)• Transfer (tRNA)• Ribsomal (rRNA)

Site of Transcription&Translation

A U G G G C U U A A A G C A G U G C A C G U U

This is a molecule of messenger RNA.

It was made in the nucleus bytranscription from a DNA molecule.

mRNA molecule

codon

Messenger RNA


A ribosome on the rough endoplasmic reticulum attaches to the mRNA

molecule.

ribosome

Ribosome


It brings an amino acid to the first three bases (codon) on the mRNA.

Amino acid

tRNA molecule

anticodon

U A C

A transfer RNA molecule arrives.

The three unpaired bases (anticodon) on the tRNA link up with the codon.

Transfer RNA


Another tRNA molecule comes into place, bringing a second amino acid.

U A C C C G

Its anticodon links up with the second codon on the mRNA.

Transfer RNA


A peptide bond forms between the two amino acids.

Peptide bond

C C G U A C

Transfer RNA


The first tRNA molecule releases its amino acid and moves off into the cytoplasm.

C C G U A C

Transfer RNA

A U G G G C U U A A A G C A G U G C A C G U U C C G

The ribosome moves along the mRNA to the next codon.

Transfer RNA


Another tRNA molecule brings the next amino acid into place.

C C G

A A U


A peptide bond joins the second and third amino acids to form a polypeptide chain.

C C G C C G

Polypeptide chain


The polypeptide chain gets longer.

G U C

A C G

The process continues.

This continues until a termination (stop) codon is reached.

The polypeptide is then complete.

Termination (stop) codon

DNA and Protein Synthesis - Summary

Use one of the codon charts on the next page to find the amino acid sequence coded for by the following mRNA strands.

CAC/CCA/UGG/UGA

___________/___________/___________/____________

AUG/AAC/GAC/UAA

___________/___________/___________/____________

CAC/CCA/UGG/UGA

___________/___________/___________/____________Histidine1st

Bas

e

2nd Base

3rd Base

Proline Tryptophan Stop

AUG/AAC/GAC/UAA

___________/___________/___________/____________Methionine Asparagine Aspartic Acid Stop

DNA and Mutations

Mutations are any changes that take place in DNA:

• Can be spontaneous or caused by mutagens• ex: Chemicals, high temperatures, UV light, radiation

• Can change the genetic code, and be replicated when forming new body cells.

• In sex cells, can be passed on to offspring.

DNA and Mutations – Lets looks at different mutations

THE DOG BIT THE CAT

DNA and Mutations - Substitution

THE DOG BIT THE CAT

• Substitution - Replace just one letter:

THE DOG BIT THE CAR

DNA and Mutations - Deletion

THE DOG BIT THE CAT Deletion: Delete just one letter (T):

THE DOG BIT HEC AT

DNA and Mutations-Insertions

THE DOG BIT THE CAT

• Insertion - Add just one letter (E):

THE DOE GBI TTH ECA T

Knowing exact cause of disease at molecular level –better

understanding of etiopathogenesis of disease process.

Correction at level of missing biochemical end product e.g.

thyroxine administration

Correction at level of excess substrate e.g. low Phe diet in PKU

Replacement of a defective enzyme e.g. Gaucher disease.

Advantages of Knowing Genetics

Replacement of defective protein e.g. Factor VIII in

hemophilia

Increasing the action of less active mutant enzyme by

giving more cofactor or co enzyme e.g. Vit. B12 for

methylmalonic aciduria

Gene therapy – an ongoing area of research which would

is expected to offer the final solution to genetic diseases.

Advantages of Knowing Genetics

Gene Therapy Gene therapy is a technique used for correcting defective genes

responsible for disease development

Gene therapy is permissible in humans at present for somatic cells only.

Major problem is complexity and efficacy

• Types of gene therapy :

Replacement : Mutant gene removed and replaced with a normal gene

Correction : Mutated area of affected gene would be corrected and

remainder left unchanged

Augmentation : introduction of foreign genetic material into a cell to

compensate for defective product of mutant gene “ only gene therapy

currently available today's”.

Gene Therapy

Documents

GENETICS an Introduction